We cannot rewind the tape of life to see how we might have been and whether humans are inevitable products of evolutionary processes, but as Kevin Davies states in his lively and enthralling Editing Humanity: [The CRISPR Revolution and the New Era of Genome Editing], our unprecedented ability to engineer genomes rapidly and efficiently offers humankind the possibility of contemplating what we might become.

Benefiting from his presence at some of the key moments in gene-editing history, and armed with humor and an enthusiastic writing style, Davies provides a compelling account of CRISPRs discovery and the shenanigans accompanying its meteoric ascendance. These include the formation of biotechs, patent disputes, fallouts and disagreements over the limits of responsible editing.

All this culminated in the untimely and unethical use of CRISPR by the scientist He Jiankui to edit the germline DNA of human embryos, an irresponsible and cavalier act that affected the heredity of two girls forever. Daviess account of this sobering episode in CRISPRs short and turbulent history reminds us of the inherent dangers of genome editing and of the ease with which technologies may be subverted for totalitarian ends. Fortunately, many essential human characteristics, including free will, do not reduce to individual genes.

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Kevin Davies' 'Editing Humanity' explores the CRISPR revolution and the ethical dilemmas that await us - Genetic Literacy Project

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It was a bumper year at the annual American Society of Hematology (ASH) meeting, with a slew of new data presented across the board. Here is a round-up of some of the key data presented.

Gilead eyes new first-line indication for CAR T Yescarta

Gileads Kite division presented new phase 2 data for its CAR T therapy Yescarta at ASH 2020 in relapsed or refractory high-risk large B-cell lymphoma (LBCL), a potential new indication.

In the phase 2 ZUMA-12 study, after a single infusion of Yescarta (axicabtagene ciloleucel), 85% of LBCL patients achieved a response, while 74% of patients achieved a complete response.

After a median follow-up of 9.5 months, the median progression-free survival, median overall survival and median duration of response were not yet reached.

Yescarta has already presented four-year survival data in patients with third-line refractory LBCL and we are now excited for what these ZUMA-12 results signal for its potential in earlier lines of treatment, said Ken Takeshita, global head of clinical development, Kite.

Yescarta was first approved by the US Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy.

Eli Lilly and Loxos BTK inhibitor shows blood cancer promise

Eli Lillys Loxo Oncology revealed some promising early-stage results for its Brutons tyrosine kinase (BTK) inhibitor LOXO-305 in patients with chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL).

LOXO-305, an oral BTK inhibitor, is designed to address acquired resistance to currently available BTK inhibitors, such as J&Js Imbruvica.

In the phase 1/2 study of the BTK inhibitor, out of 139 CLL/SLL patients who were efficacy-evaluable, 88 responded to treatment, with 19 partial responses with ongoing lymphocytosis, 45 with stable disease and one with progressive disease.

In a subgroup of patients previously treated with a BTK inhibitor, the overall response rate was 62%, which increased to 84% for those with ten months or more follow-up.

It is important to note that the patients included in this study were heavily pre-treated, with all CLL/SLL patients having received a median of three prior lines of therapy.

Vertex/CRISPR Therapeutics make headway in sickle cell and beta thalassaemia

Also presenting data at ASH were Vertex and CRISPR Therapeutics, whose gene-editing therapy CTX001 scored some promising results in transfusion-dependent beta thalassaemia (TDT) and sickle cell disease (SCD) patients.

The CRISPR/Cas9-based gene therapy was investigated in a total of ten patients, seven of which had TDT and three with SCD.

All TDT patients treated with CTX001 were transfusion independent at last follow-up and all SCD patients were free of vaso-occlusive crises (VOCs), the companies announced at the meeting.

These are the first published results from CRISPR/Cas9 therapy in people with a genetic disease and represent an important milestone in medicine and for our collaboration with CRISPR Therapeutics, said Reshma Kewalramani, chief executive officer and president, Vertex.

Most importantly, this data represents a critical step in our effort to bring transformative and potentially curative therapies to patients, he added.

bluebird bios beta thalassaemia gene therapy Zynteglo scores promising long-term data

bluebird bio also posted long-term data for its own beta thalassaemia gene therapy Zynteglo (betibeglogene autotemcel) at ASH 2020.

The new data reflects up to six years of safety and efficacy data for the gene therapy in patients with TDT.

Among 32 patients enrolled in the 13-year, long-term LTF-303 study, 64% of patients treated in the phase 1/2 portion and 90% in the phase 2 portion achieved transfusion independence (TI).

In the LTF-303 study, all patients who achieved TI remained free from transfusions, with the median duration of ongoing TI coming in at 39.4 months.

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ASH 2020: Gilead eyes new Yescarta indication, Vertex/CRISPR make headway in sickle cell and more - PMLiVE

Recommendation and review posted by Bethany Smith

CiBER-seq dissects genetic networks

Cells integrate environmental signals and internal states to dynamically control gene expression. Muller et al. developed a technique to dissect this cellular logic by linking targeted, genome-wide genetic perturbations with a deep-sequencing readout that quantitatively measured the expression phenotype induced by each perturbation. The method, dubbed CiBER-seq, was able to recapitulate known regulatory pathways linking protein synthesis with nutrient availability in budding yeast cells. Unexpectedly, the authors found that the cellular logic also appears to consider protein production machinery in this decision. By uncovering additional facets of this deeply conserved pathway, the findings demonstrate the utility of comprehensive and quantitative CiBER-seq profiling in mapping the gene networks underlying cellular decisions.

Science, this issue p. eabb9662

Systematically profiling the effects of genetic perturbations is a powerful approach that has revealed the molecular basis for a wide range of biological phenomena. The simple, programmable DNA recognition of CRISPR-Cas9 enables genome-wide genetic analysis in human cells and many other systems. Cas9 is guided by a short RNA to a complementary sequence in the genome, where it can introduce mutations or alter gene expression. Pooled libraries of guide RNAs (gRNAs) that individually target each gene in the genome allow us to introduce genetic perturbations systematically into a population of cells. A key challenge is measuring the phenotypic effects caused by individual guides in these pooled libraries and linking these phenotypes back to the associated gRNA, thereby finding the gene that is responsible.

Molecular phenotypes such as gene expression changes provide a clear and sensitive measure for many cellular processes. We sought a general approach to profile how the expression of a particular gene of interest changed when other genes were perturbed. We began with a library of gRNAs, each disrupting one gene, and linked these guides with an expression reporter containing a guide-specific nucleotide barcode. gRNAs that alter reporter expression will change the abundance of the expressed RNA barcode specifically associated with that guide. Deep sequencing of these expressed barcodes quantifies each of these guide-specific reporter expression effects individually within a pooled, complex population. We have implemented this strategy by combining CRISPR interference (CRISPRi) with barcoded expression reporter sequencing (CiBER-seq).

We used CiBER-seq to profile the responses of several yeast promoters tied to a range of biological functions. Each promoter yielded a distinct pattern of responses that could be understood in terms of its known function and regulation. For example, we rediscover the control of MET6 expression by regulatory ubiquitylation and connect the bud scar protein Cwp1 to other genes required for budding and cytokinesis. Our analysis of the HIS4 promoter, a well-characterized target of the integrated stress response, yielded a range of genetic perturbations that activate this pathway by causing the accumulation of uncharged transfer RNAs (tRNAs). We also uncovered a notable role for tRNA depletion in this response, as impaired tRNA biogenesis activated HIS4 expression through a distinct pathway. In order to understand this regulation, we carried out genetic interaction analysis and looked for quantitative deviations in CiBER-seq profiles caused by the introduction of a second genetic perturbation. We also developed an indirect CiBER-seq approach to measure translational and posttranslational regulation, which both play roles in the signaling pathways upstream of HIS4.

CiBER-seq produces comprehensive phenotypic profiles that offer insights into gene function and regulation. These high-throughput and quantitative phenotypic measurements are also well suited for the systematic measurement of genetic interactions, which contain rich information about the operation of biological processes. This approach can be applied to study a wide range of transcriptional, translational, and posttranslational regulatory responses, and it has the potential to shed light on many areas of biology.

CRISPR-Cas9 gRNA cassettes are linked with transcriptional reporters containing specific barcodes. The RNA-to-DNA ratio for each barcode, measured by deep sequencing, reveals the reporter expression phenotype induced by each gRNA.

To realize the promise of CRISPR-Cas9based genetics, approaches are needed to quantify a specific, molecular phenotype across genome-wide libraries of genetic perturbations. We addressed this challenge by profiling transcriptional, translational, and posttranslational reporters using CRISPR interference (CRISPRi) with barcoded expression reporter sequencing (CiBER-seq). Our barcoding approach allowed us to connect an entire library of guides to their individual phenotypic consequences using pooled sequencing. CiBER-seq profiling fully recapitulated the integrated stress response (ISR) pathway in yeast. Genetic perturbations causing uncharged transfer RNA (tRNA) accumulation activated ISR reporter transcription. Notably, tRNA insufficiency also activated the reporter, independent of the uncharged tRNA sensor. By uncovering alternate triggers for ISR activation, we illustrate how precise, comprehensive CiBER-seq profiling provides a powerful and broadly applicable tool for dissecting genetic networks.

Link:
CiBER-seq dissects genetic networks by quantitative CRISPRi profiling of expression phenotypes - Science Magazine

Recommendation and review posted by Bethany Smith

While breast cancer is usually considered a disease that only affects women, anyone with breast cells and tissue can be diagnosed with breast cancer, males included. Even so, male breast cancer is rare.

"This isn't a disease that's 'just for women.' Patients often don't realize this which can, unfortunately, lead to delays in diagnosis," says Abisola Olulade, MD, a family medicine physician at Sharp Rees-Stealy Downtown in San Diego, California. "In the United States, male breast cancer represents between 0.5% and 1.0% of all breast cancers diagnosed each year. This means that about one out of every 100 breast cancers diagnosed in the United States is found in a man."

In this article we'll discuss the most common forms of male breast cancers, its symptoms, and potential risk factors.

Male breast cancer occurs when malignant cells form in the tissues of the breast. Common forms of male breast cancer include:

Unfortunately, doctors are still unsure of the exact causes of breast cancer, though genetics and increased levels of estrogen may be risk factors.

In particular, increased estrogen is associated with conditions like liver disease, obesity, and certain hormone therapies like anti-androgen therapy, says Monisha Bhanote, MD, a triple board-certified physician and cytopathology specialist in Jacksonville Beach, FL. where she runs her own private practice.

"Hereditary causes may include BRCA2 mutation carriers, PTEN mutation (Cowden syndrome), and CHEK2 mutation carriers," says Bhanote

BRCA1 and BRCA2 (BReast CAncer genes 1 and 2) are genes that are related to breast cancer risk. While everyone has both BRCA1 and BRCA2 genes, some people inherit a gene mutation in one or both of these genes. This mutation increases the risk of developing breast cancer.

"Men with BRCA mutations are recommended to have annual screening," says Bhanote. "Examination for any masses, nipple discharge, or skin dimpling/puckering on a daily basis will

be helpful."

Additional factors that may increase a person's risk are medications such as antidepressants, marijuana, and radiation from cancer treatment.

Male breast cancer spreads in the same way that female breast cancer spreads, through the lymphatics and blood vessels. An estimated 520 men will die from breast cancer this year.

Signs and symptoms of male breast cancer can include:

While finding a lump on one or both of your breasts can be alarming, finding a lump doesn't necessarily mean that you have breast cancer. It could be gynecomastia or enlarged breast tissue.

Though gynecomastia has many causes, liver disease and drugs or medications that contain high doses of testosterone account for about 25% of gynecomastia cases, according to Harvard Men's Health Watch.

Gynecomastia is often benign and resolves on its own. That being said, it's still a good idea to see your doctor if you notice any lumps or changes, especially if you're experiencing pain or discomfort.

Because men are less likely to receive a mammogram, it's important to learn how to perform a male self-breast examination. As a patient, it's imperative to become familiar with your body so you can advocate for yourself and notice when changes occur. Here's a quick step-by-step guide on how to self-check your breasts at home:

You can also check your breasts while lying down. To do this, set a pillow underneath your right shoulder and bend your right arm over your head. Use the fingertips of your left hand to check all areas of your breast and armpit. Once you're finished, switch the pillow to your left shoulder and repeat this process.

If you're uncomfortable doing a self-breast examination, or you fear that you're not doing it correctly, ask your physician to perform a clinical breast exam for you. Depending on how the examination goes, your physician may order a mammogram, an ultrasound, or an MRI.

If you're diagnosed with male breast cancer, your treatment plan will depend on how far the cancer has spread. Practicing monthly self-breast exams, in addition to receiving a breast examination by your physician, could improve your chances of detecting breast abnormalities early. Early detection is the key to successful treatment.

Possible treatments for male breast cancer include:

Although researchers can't pinpoint the causes of breast cancer in men, they have found a few risk factors.

Risk factors that may lead to developing male breast cancer include:

"Unfortunately, there isn't anything you can do to prevent male breast cancer," says Nicholas Jones, MD, FACS. "However, you can lower your risks by being active, and limiting your alcohol consumption."

In addition, avoiding hormonal supplements, such as sexual performance enhancement supplements, may help to prevent male breast cancer. According to a 2019 study, the use of hormonal male enhancement supplements can lead to the higher levels of androgens, which may cause the growth of tumors.

Though the likelihood of developing male breast cancer is low, it's important to pay attention to your body. If you notice any changes in your skin color, new rashes, lumps, or bumps, you should seek medical help right away.

"There isn't a great screening tool for men," Jones adds. "The best action is to know your body, live a healthy lifestyle and if you notice anything out of the norm, visit your doctor. Specifically for male breast cancer, any change involving the nipple may be a sign that there is an underlying cancer."

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Yes, men can get breast cancer here are the symptoms to watch for - Insider - INSIDER

Recommendation and review posted by Bethany Smith

The COVID-19 lockdown had brought some cheer for Andheri-based Kamat couple as they welcomed their first child - Teera - on August 14. But soon things went awry when their daughter was diagnosed with a rare genetic disorder - Spinal Muscular Atrophy (SMA). Three-month-old Teera's parents - Mihir, 35, and Priyanka Kamat, 33, have been doing everything possible for their daughter's treatment but the biggest challenge for them is to raise '16 crore for a single shot of gene therapy, the only way she can survive.

Teera with her parents Mihir and Priyanka Kamat

Teera has been diagnosed with SMA Type 1, which is said to be a more serious form of the disorder. Speaking to mid-day, Mihir, who works for a software company, said, "Teera was born a happy and cheerful baby. As weeks went by, we noticed she was having heavy breathing patterns and it would also take a long time to feed her. Very soon, she developed multiple issues like severe dehydration, heavy breathing, choking on feeds etc, and we finally found a doctor in our area who recommended we start bottle feeding."

"On the day of her vaccination (September 30), her doctor noticed that she was choking on her first drops of vaccine. She was also not being able to resist with her hands and the right leg wasn't moving," Mihir recalled.

"The doctor referred us to a paediatric neurologist who mentioned that Teera might have hypotonia, slow reflexes, paradoxical respiration and a weak cry. Following her EMG and genetic test, we got to know that she is suffering from SMA Type 1. The next shock was the cost of the drug, which needs to be imported from the United States. Teera needs it before she turns six months old, the golden period to save her. We started doing a bit of research on the disorder and found out about some foreign nationals who have written positively about the treatment and how they could 'crowd fund' such a large sum by registering on a similar platform," added Mihir.

"We registered our daughter's details with crowd funding platform Impact Guru and in less than a month 8,187 donors contributed nearly '2.36 crore, said the couple. Mihir further said, "Our consulting paediatric neurologist Dr Neelu Desai has already registered Teera for the Switzerland HQ Novartis pharma company global lottery, where selected registered patients get the drug free of cost." "Just three weeks ago Teera had to be rushed to Holy Spirit hospital in Andheri East, as she got choked during her feed and turned pale. She had to be kept at the hospital for the next couple of days," her father said.

SMA is a progressive, rare genetic disease that is caused by missing genes or those that don't work properly, which might be survival motor neuron 1 (SMN1). This gene is basically the blueprint responsible for making a protein required for the survival of the spinal nerve cells. Without this SMN gene the cells in the body start to die and motor neuron cells become weaker thus causing muscle weakness in every part of the body below the neck.

Piyush Jain, co-founder and CEO of ImpactGuru.com, said, "In one month, 8,187 donors have contributed '2.36 crore. This is Impact Guru's highest single fundraiser. Among the donors is a noted Bollywood actor, who donated '5 lakh We are currently working towards ensuring the target is met by all means."

Dr Neelu Desai

Dr Desai said, "Teera is one of the youngest patients I'm treating at the moment. If she doesn't get the special gene therapy, then she might survive for about two years. Until last five years, there was no treatment for SMA, but now we have gene therapy, for which Teera has been registered."

She further said, "This is a rarest of rare disorder (1 in 5,000 infants suffer from it world over). In case a baby does not develop proper motor skills or his/her body feels very soft then parents should consult paediatricians. Parents who have a child with SMA, have 25 per cent chances of the same disorder developing in the subsequent pregnancies, which can be confirmed in the first few months by doing a genetic test."

Link to the fundraiser - https://www.impactguru.com/fundraiser/donate-to-teera

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Mumbai: Baby with genetic disorder needs Rs 16 crore therapy to live - Mid-day

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MedicalResearch.com Interview with:

Steven Pipe, MDProfessor of Pediatrics and PathologyLaurence A. Boxer Research Professor of Pediatrics and Communicable DiseasesPediatric Medical Director, Hemophilia and Coagulation Disorders ProgramDirector, Special Coagulation LaboratoryUniversity of Michigan

MedicalResearch.com: What is the background for this study?

Response: Hemophilia B is an inherited bleeding disorder where patients are missing clotting factor IX (9), a critical blood clotting protein.Patients with a severe deficiency are at risk for traumatic and spontaneous bleeds primarily into joints.Repeated bleeding into joints causes more than acute pain and swelling but also leads to inflammatory and degenerative changes in joints that eventually leads to severe debilitating arthritis that can be crippling.To try to prevent this, patients as young as infants are placed on regular infusions of clotting factor IX concentrates.The relatively short half-life of factor IX means patients must infuse on average once to twice a week.These can only be delivered intravenously parents and then patients themselves have to learn this.Prophylaxis must be continued lifelong to try to prevent bleeding events and protect joint health over the lifespan.This is a tremendous burden on the patient and their caregivers.

Even with regular prophylaxis, joint bleeds may still occur and arthropathy may still ensue.This is because the blood levels often reach critically low levels prior to the next infusion.Gene therapy aims to deliver a functional copy of the factor IX gene such that the patients own liver will make a continuous supply of factor IX that is delivered to the bloodstream.At steady state with levels close to or within the normal range, patients would no longer be subject to bleeding events and would not require prophylaxis any longer.We hope that such a one-time treatment would produced durable, functionally curative levels of factor IX.

MedicalResearch.com: What are the main findings?

Response: The 3 key takeaways are:

MedicalResearch.com: What should readers take away from your report?

Response: I think it is best to characterize this as a treatment that liberates patients with hemophilia from the burden of repeated prophylactic infusions of clotting factor to protect them from recurrent bleeding events.Gene therapy offers a chance to have steady state levels of factor in the blood that would eliminate risk for spontaneous and even traumatic bleeding events.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: These are very encouraging results maximizes eligibility for patients by being able to treat in the presence of pre-existing neutralizing antibodies.Results are in a range that allow for cessation of prophylaxis and continued bleed protection.Results appear to be durable through the follow up period to date.The 26 week endpoint was a co-primary endpoint.The other endpoints are factor IX activity at 52 weeks and annualized bleeding rate over the 52 weeks post-dosing. Those endpoints should be analyzed in 2021 and decisions could then be made on submission for regulatory review.

MedicalResearch.com: Is there anything else you would like to add? Any disclosures?

Response: This could be potentially clinical practice changing, if approved. This looks to be a transformative therapy for patients and could be an option for patients across the adult lifespan we treated patients from age 19 through 75. Our patient population have been looking forward for a long time for a one-time therapy like this that would provide lasting protection from bleeds.

I have served as a paid consultant to uniQure and chair the Steering Committee for the global clinical trial program

Citation: ASH2020 Oral Abstract

First-in-Human Gene Therapy Study of AAVhu37 Capsid Vector Technology in Severe Hemophilia A BAY 2599023 has Broad Patient Eligibility and Stable and Sustained Long-Term Expression of FVIII

Steven W. Pipe, MD1, Francesca Ferrante, MD2*, Muriel Reis3*, Sara Wiegmann4*, Claudia Lange5*, Manuela Braun5*and Lisa A Michaels6*https://ash.confex.com/ash/2020/webprogram/Paper139803.html

The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.

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Gene Therapy Liberates Hemophilia B Patients from Requiring Regular Infusions of Clotting Factor - MedicalResearch.com

Recommendation and review posted by Bethany Smith

This article was originally published here

Lab Invest. 2020 Dec 9. doi: 10.1038/s41374-020-00520-2. Online ahead of print.

ABSTRACT

Disorders involving injury to tissue stem cells that ensure normal tissue homeostasis and repair have potential to show unusually devastating clinical consequences. Acute graft-versus-host disease (aGVHD) is one condition where relatively few cytotoxic immune cells target skin stem cells to produce significant morbidity and mortality. By analogy, SARS-CoV-2 is a vector that initially homes to pulmonary stem cells that preferentially express the ACE2 receptor, thus potentially incurring similarly robust pathological consequences. In older individuals, stem cell number and/or function become depleted due to pathways independent of disease-related injury to these subpopulations. Accordingly, pathologic targeting of stem cells in conditions like aGVHD and COVID-19 infection where these cells are already deficient due to the aging process may have dire consequences in elderly individuals. A hypothesis is herein advanced that, as with aGVHD, lung stem cell targeting is a potential co-factor in explaining age-related severity of COVID-19 infection.

PMID:33299126 | DOI:10.1038/s41374-020-00520-2

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COVID-19 and graft-versus-host disease: a tale of two diseases (and why age matters) - DocWire News

Recommendation and review posted by Bethany Smith

TipRanks

Investing is all about profits, and part of generating profits is knowing when to start the game. The old adage says to buy low and sell high, and while its tempting just to discount cliches like that, theyve passed into common currency because they embody a fundamental truth. Buying low is always a good start in building a portfolio.The trick, however, is recognizing the right stocks to buy low. Prices fall for a reason, and sometimes that reason is fundamental unsoundness. Fortunately, Wall Streets analysts are busy separating the wheat from the chaff among the markets low-priced stocks, and some top stock experts have tagged several equities for big gains. These stocks are trading low now but the reasons are not necessarily bad for investors.Weve used the TipRanks database to pull up the data and reviews on two stocks that are priced low now, but may be primed for gains. Theyve been getting positive reviews, and despite their share depreciation, they hold Buy ratings and show upwards of 60% upside potential.Digital Media Solutions (DMS)We will start with Digital Media Solutions, an adtech company which connects online advertisers with customers through performance-based branding and marketplace solutions. DMS boasts a powerful consumer intelligence database, which it uses to fine-tune customer acquisition campaigns while offering advertisers accountability for the project budget.DMS went public in July of this year, via a merger with a special purpose acquisition company, Leo Holdings. The combination took the DMS name for the ticker, and initiated trading at $10 per share. The stock has been volatile since, and is currently down 27% since it started trading.Digital advertising is a huge and growing sector, worth $100 billion in 2019 and expected to reach $130 billion by the end of next year. DMS has a solid piece of that cash cow, and the Q3 numbers demonstrate that. Quarterly revenue hit a company record, of $82.8 million, which was up 10% sequentially and 44% year-over-year. Of that total revenue, the company saw a gross profit of $25.1 million, for a 30% gross margin. All in all, DMSs first quarter as a publicly traded company showed strong results.Covering the stock for Canaccord is analyst Maria Ripps, who is rated 5 stars by TipRanks, and stands in the top 1% out of more than 7,100 stock analysts. The company saw meaningful volume growth from both new and existing clients, with particular strength from its auto insurance business along with the eCommerce, education, and non-profit verticals We continue to think investors will gradually come to appreciate DMS similarities with other leading digital marketing peers that trade at more premium valuations, and expect multiple expansion over time as the story becomes better understood, Ripps noted.To this end, Ripps rates DMS stock a Buy, and her $15 price target suggests an upside of 106% from the current share price of $7.20. (To watch Ripps track record, click here)Overall, DMS Moderate Buy consensus rating is based on 2 recent reviews, both positive. The stock has an average price target of $14, which indicates a 92% upside potential. (See DMS stock analysis on TipRanks)ViaSat, Inc. (VSAT)From digital advertising we move on to digital networking. ViaSat provides customers with high-speed broadband access through a secure satellite network system. The company serves both military and commercial markets, meeting the growing need for secure communications links.The anti-coronavirus shutdown policies have particularly hard on ViaSat. This may sound counterintuitive, as online networking has been busier than ever, but a large segment of ViaSats business comes from the airlines, and with air travel first grounded and still facing depressed travel volumes, ViaSats shares have yet to recover from their February/March swoon.On a positive note and one that is indicative of the essential nature of secure satellite communications in todays networked economy ViaSat reported $577 million in Q3 contract awards, representing a 29% yoy gain. For the year to date, the company has seen awards totaling $1.9 billion, which is up 5% from this time last year. The third quarter (the companys fiscal Q2) revenues and earnings were somewhat mixed, reflecting both the increase in contract awards and the decline in airline business. Revenues were $554 million, down 6% yoy, but up almost 4% sequentially. EPS was 3 cents per share, beating the predicted 5 cent loss by a wide margin.JPMorgan analyst Philip Cusick writes of ViaSat: [We] believe long-term growth levers remain intact highlighted by record segment backlog of $1.1b We view ViaSat as a satellite innovation leader and believe the companys future ViaSat-3 fleet will accelerate growth in satellite services over the coming years. At the same time, we see a long-term government systems tailwind driven by the companys radio portfolio, mobile broadband, and SATCOM.In line with his bullish comments, Cusick rates VSAT shares an Overweight (i.e. Buy), and his $60 price target implies ~72% upside on the one-year time horizon. (To watch Cusicks track record, click here)Overall, the stock has 5 recent reviews, including 3 Buys and 2 Holds. Shares are priced at $34.14, and the average price target of $55 suggests a 61% upside potential from that level. (See VSAT stock analysis on TipRanks)To find good ideas for stocks trading at attractive valuations, visit TipRanks Best Stocks to Buy, a newly launched tool that unites all of TipRanks equity insights.Disclaimer: The opinions expressed in this article are solely those of the featured analysts. The content is intended to be used for informational purposes only. It is very important to do your own analysis before making any investment.

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Avenoir Cosmetics Launches Cell Repair Serum - Clinical Strength to Enhance Skin Tone & Minimize Appearance of Sunspots, Blemishes, Discoloration,...

Recommendation and review posted by Bethany Smith

Even while legalization and regulations are in flux throughout the Americas region and around the globe, cannabis beauty is making tremendous progress.

The cannabis market is emerging very, very rapidly around the world, said Shane MacGuill, Senior Head of Nicotine and Cannabis at Euromonitor during a webinar last month reviewing the global cannabis industry across market sectors and showcasing the launch of the market research companys newest Passport Research System focus: cannabis. And he added,the market is currently heavily concentrated in US Canada.

This year2020was the year that both Amway and Avon launched CBD skin care. Avon made the announcement first. In April, as Cosmetics Design reported, the social-selling beauty maker announced plans for a new vegan skin care line that would include a CBD oil. And today, Avon has 3 CBD products in its portfolio: Green Goddess Facial Oil, Veilment CBD Soothing & Nourishing Body Cream, and Veilment CBD Nourishing Body Cream, all of which contain 100mg of CBD. Though as the online product descriptions note, our collection does NOT contain THC. The only high youll get is knowing your skin feels cool, calm and collected.

Amway, as Cosmetics Design reported, announced the launch of its new Artistry Skin Studio product collection in September 2020. And that product line now includes Artistry Studio Zen Daze Ahead Facial Oil +300 mg CBD.

Colgate also got involved in the CBD Beauty market this year. In January the company announced an acquisition deal to buy Hello Products and the following month, Hello launched its CBD product collection, as Cosmetics Design reported. Hello is best known for its oral care products but the brand also makes CBD lip balm, for instance.

Ayuna, a luxury skin care brand out of Spain, just launched the latest limited-edition product in its sought-after Terra collection at the start of November: Terra Bella.

There are no cannabinoids, no THC, no CBD in this new cream. But the Terra Bella face cream is formulated with a remarkable extract derived from cultured Cannabis Sativa stem cells, as Isabel Ramos, Chief Scientific Officer at Ayuna, tells Cosmetics Design.

And the ingredient does something truly extraordinary: it instigates communication between the skin microbiome and the brain, explains Ramos. This topical ingredient is, she says, the first known instance of a skin care input helping and demonstrating that microbiota are acting on [or affecting] how we feel.

As the Ayuna example illustrates, theres a lot more to cannabis beauty than the ever-enchanting CBD. In fact, the entire cannabis plant and a full range of cannabinoid molecules are shaping the future of this buzz-worthy cosmetics and personal care category.

In October, Jennifer Grant, a biomedical engineer turned beauty entrepreneur launched a clean skin care brand called empyri that relies on upcycled cannabis root at its hero ingredient. And not long before that news made headlines here on Cosmetics Design, the biotechnology company behind brands like Bissance and Pipette, announced having successfully scaled production of biotech CBG (one of many cannabinoids naturally occurring in cannabis) for use in skin care product formulations. So while CBD beauty is here to stay, theres much more to Cannabis Sativa and to cannabis beauty than this one molecule. Ready to learn more? Revisit all the top CBD beauty news from 2019 here on CosmeticsDesign.com.

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CBD: the beauty ingredient trend that can't be stopped - CosmeticsDesign.com USA

Recommendation and review posted by Bethany Smith

In the second year of Endpoints Newsbudding tradition of highlighting women blazing trails in biopharma R&D, weve seen a number of firsts.

For the first time, the biggest story in R&D is also top of mind for a world anxious to end the most devastating health crisis in decades. With its sweeping effects, the Covid-19 pandemic is turning the daily routines for many working women upside down, taking a toll on not just their physical and mental health, but also their career prospects. At the same time, the biotech industry is doing some serious soul searching with a new scorecard and plan for diversity and inclusion.

It is more important than ever to shine light on the growing number of women who have scaled the heights of drug discovery and development even though the odds are stacked against them, breaking open paths in labs and C-suites that can be followed by future generations, some of whom they are also actively nurturing and mentoring.

We set out this year with a dual goal: to celebrate women at the forefront of subduing Covid-19 either with diagnostics, vaccines or treatments and to honor those working day in and day out to address other equally pressing medical needs.

Profiles are, by definition, snapshots. Some of the women recognized in our 2019 special report have since become household names: Jennifer Doudna became a Nobel laureate for her pioneering work in CRISPR gene editing and zlem Treci helped create the worlds first vaccine proven effective against Covid-19. Even in the short period since we interviewed this years honorees, weve seen them mark new milestones, from taking a biotech public to scoring historic clinical data and regulatory authorizations.

We hope our profiles capture a unique moment in history as these highly accomplished figures take us with them down memory lane to illustrate what brought them to this moment and how they are helping other women do the same if not even more.

We hosted an online live event to introduce this years top women in biopharma R&D, followed by a panel discussion on what it will take to truly achieve gender diversity in the industry. You can watch the full event here.

Carolyn Bertozzi wasnt exactly looking to start a company when she tweeted about a preprint her group posted on ChemRxiv last November. The paper described LYTACs molecules that can tag extracellular proteins for degradation.

She was heading out to the American Chemical Society Conference in Orlando to talk about the project, led by a postdoc in her Stanford lab named Steve Banik.

(Steve) was about to go on the academic job market, so its a good time for me to go and sort of talk about his work publicly and drop his name and get him some name recognition, she recalled.

Within 24 hours, though, she got a dozen phone calls from venture capital groups who picked up on the preprint. There was a proliferation of startups utilizing and improving on PROTACs a targeted degradation technology born out of Craig Crews academic work at Yale but that magic was limited to intracellular proteins. Bertozzi was a self-described jealous fan of Crews work because glycoproteins, the subject of her own research, reside exclusively on cell surfaces; it turned out VCs had also been wishing there were ways to target secreted and membrane proteins.

In the end, she found Versant Ventures to be the best fit for the science. Now, Lycia Therapeutics, which unveiled a $50 million Series A just a few months ago, has been taking off like a rocket ship, she said.

The enthusiasm from investors might be expected for a scientist and entrepreneur whose last biotech creation, Palleon Pharmaceuticals, recently reeled in $100 million in fresh financing. Redwood, the one that came before, recently reported Phase I data as a subsidiary of the CRO giant Catalent. Then there are the handful of diagnostics players that she created with researchers under her wing.

But for Bertozzi, its all about timing.

Her first experience with entrepreneurship a biotech startup she co-founded in the late 1990s after completing a postdoc with Steve Rosen at UCSF actually ended in failure. Thios Pharmaceuticals, as it was known, had zeroed in on a target for sickle cell acute vaso-occlusive crisis and in-licensed a molecule that worked in a similar way as two therapies approved by the FDA late last year.

They raised $10 million for it, a respectable amount for a Series A at that time, but it wasnt enough to sustain the 30-person company when investors decided not to continue funding it. The drug was shelved as Thios closed up shop.

It was always very heartbreaking to us that we couldnt have brought that to those patients 15 years earlier, Bertozzi said. But thats how it goes in this business, and every company has a story like that.

In her day job as an academic, Bertozzi is known for spearheading a glycorevolution: developing chemical tools and technologies to elucidate the roles that complex sugar structures play in biological systems. Glycans, as she learned during her doctorate, are an order of magnitude more technically complex than polypeptides and oligonucleotides because of their structural diversity. But papers dating as far back as the 1950s have suggested they do play a role in diseases such as cancer, and spectacular breakthroughs in chemical synthesis the challenge that drew her to the space initially have helped scientists make inroads in their study.

Her biggest breakthrough which won her a MacArthur genius grant at age 33 came in what she coined bioorthogonal chemistry, a way for chemical reactions to take place within biological systems.

Both the tools and her deep knowledge of glycobiology provided the foundation for the subsequent technologies her group would later develop. Site-specific chemical modification of recombinant proteins promised to make better antibody-drug conjugates (ADC) than the very sloppy molecules that characterized the first generation of ADCs; digging deeper into new findings on how cancer cells sprouts sugars on their surfaces to evade the immune system led them to bispecific antibody-enzyme constructs that target the siglec-sialic acid pathway, billed as the next big I/O checkpoint; and utilization of lysosomal trafficking shuttles one of the first things you learn when you study glycobiology gave birth to chimeras that send unwanted extracellular proteins to the lysosome for targeted degradation.

More so than any particular technology, though, she considers the young scientists who trained with her and are now standing on their own feet her most important achievement.

Carolyns genius is not only in the research she leads, but also in those she recruits, Mireille Kamariza, a former PhD student, said. Now a junior fellow at Harvard University, she co-founded with Bertozzi a public benefit corporation to advance a point-of-care diagnostic device for tuberculosis.

She has an uncanny ability to bring out the best in people, Kamariza added. She leads by example and gives unyielding support to her students interests and pursuits.

Now 54, Bertozzi recently found herself reflecting on her career after the death of late Supreme Court Justice Ruth Bader Ginsburg. Harvard, after all, had only integrated with Radcliffe a few years before shed start undergraduate studies there.

I consider myself to be in sort of the first generation where you see a critical mass of women who made it through the academic pipeline and into industry, she said. There arent many of us, but you can count us. Were visible.

Having seen every shade of gender discrimination and bias (show me a woman who hasnt), Bertozzi is leveraging her influence as the co-director of Stanford ChEM-H to bring in more voices from outside the usual suspects reaching out and forging relationships with public universities and institutions serving underrepresented communities to find talent that is hiding in plain sight.

In previous interviews, shes noted that part of what got her hooked in those first organic chemistry classes was how molecules have personalities like people. So I couldnt help but ask: What molecule would she be?

The answer was surprisingly simple. She aspires to be a monoclonal antibody.

They multitask all over the place, she said. In fact, all of the next-generation biologics out of her lab have had antibodies as their backbones.

I have gotten so much mileage out of antibodies, she said. And so I would like to think maybe my students could get the mileage out of me that same way. That would be my aspiration.

Thats not all: Oh, and they are glycosylated. Amber Tong

Kathy Bowdish was sitting down at a San Diego restaurant after her first pitch meeting in 1997 when one of the potential investors turned and asked her a question: Does your husband know youre doing this?

Taken aback, Bowdish, 39 at the time, said yes, and that part of this was his idea. Of the 12 angel investors at the table that day, the concerned citizen was the only one who didnt decide to back her first startup. And he was the only one who didnt get a cut of the profits three years later, when Bowdish sold the startup to Alexion for 10 times their investment.

When the press release for the buyout hit the wire, her phone rang. It was the lone investor.

If you do this again, I want to be on speed dial, the investor told her. Bowdish looks back on that moment with victory-tinged humor: Clearly, his question had been troubling him.

The seed investor had made two mistakes. One shouldve been obvious at the time: plain misogyny. But the other would only become fully apparent over the ensuing 23 years as the young scientist-executive enmeshed herself in a series of top biotechs and eventually was handpicked by Elias Zerhouni to lead a unique and under her direction fruitful venture in Sanofis upper ranks.

He had underestimated Kathy Bowdish.

Bowdish would prove over the years a rare triple-threat in biotech: a brilliant scientist who could handle the business side but also had the poise and emotional IQ to massage needed personal relationships and wheedle folks who could get things done. After nearly two decades in biotech, she used those skills to build powerful new companies at Sanofi. And when the winds changed there, she pivoted mid-career to what she first learned to do in San Diego: build a company with cutting-edge science from the ground up.

Kathy impressed me because she had been CSO, she was a very good scientist, Zerhouni told me. But she had this very special natural calm A very thoughtful calm, a resilience. She had this analytical mind.

Bowdish is now working from her home in Cambridge, trying to get a three-person,RNA-based startup off the ground with $5 million in seed cash. Its a significant departure from her Sanofi perch, but its a position she knows and a place shes thrived before.

The daughter of an engineer and an artist, Bowdish was seduced by the cerebral yet creative challenge that scientific problems posed. After studying biology at William & Mary, she moved to the West Coast, where she was quickly recruited for a position at Scripps Research and worked with Richard Lerner on the then-pioneering field of catalytic antibodies.

She was clever and ambitious, devising new ways of sequencing antibodies in an era before you could simply plug them into RNA-Seq. She left to get a PhD at Columbia University, and picked a yeast lab because yeast multiplies like microbial rabbits, which meant you could do a lot of genetics work in a single program.

A postdoc followed, but she soon grew impatient. These were still early days for antibodies. She pitched Lerner on the idea of building a company around the work they did on combinatorial antibody libraries basically discovery engines in a test tube.

His immediate question to me was can you live without a salary for 6 months? Cause thats what its going to take in order to raise the money. And I said yes, she said. I was pretty naive maybe the naivet was a good thing.

The investors (but one) came on board, Bowdish finagled her way into some cheap equipment, hired another scientist a woman and for a year the pair worked at the bench to discover antibodies that would activate, rather than inactivate, receptors. She shifted over to a full CEO role after year one, and after year three Alexion bought the company for $41 million, betting that it could serve as their discovery engine.

She stayed at Alexion until 2007, by which time she was a sought-after name for biotechs with big ideas. Investors recruited her to relaunch Anaphore, a Danish biotech trying to develop antibody-like alternatives that were more selective or more potent. They struggled for years, which worried Bowdish until she realized every company in the space was struggling. It taught her a valuable lesson about what makes for good translational science.

You just cant beat evolution, she said.

Then ARCH and Flagship came calling. They had funded a bold Bob Langer idea for delivering proteins inside cells. Quickly, she realized they had to start testing this in animals to have any idea if it worked. And quickly they learned that it didnt everything went to the liver. So she leveraged their tech into antibody-drug conjugates.

It looked really good in vitro, she said. In vivo, not so much.

By then it was 2013. and Bowdish had been in the league for 16 years, helping run five biotechs on both coasts. She knew the game, but she was curious: about pharma, that behemoth in the background, and about investment, a general-esque perch from which she could ponder and evaluate. At the same time, Zerhouni was conceiving a new initiative at Sanofi: Sunrise, a way of giving biotechs the resources and expertise of pharma while allowing them to flourish on their own. It married the two.

Bowdish got the job, beating out such biotech titans as Michael Gilman. Inside, she learned how pharma worked and she built new companies. She was, Zerhouni said, singlehandedly responsible for MyoKardia, the cardiovascular upstart that Bristol Myers Squibb recently purchased for $13 billion. She found them, he said, designed a deal to get them the best resources and convinced Sanofi leadership to get on board.

Shes able to move the needle from a pretty established sort of approach to an innovative one, Zerhouni said. Shes a change agent.

Then Paul Hudson came in, reshuffled Sanofi, and Bowdish found herself on the outs (Sanofi also pulled out of her MyoKardia deal, a blunder that cost them a cool $1 billion). She went home, relaxed and did what she always does dove back into the literature: papers on immunology, diabetes, biomolecular condensates, whatever fascinated her.

Eventually, a recruiter called. She realized it was time to get moving. She mentioned to Gilman they had stayed in touch after a conference that she was on a hunt, and Gilman put her in touch with Genzyme Ventures vet Alan Waltz, who was looking for a CEO for a company that would develop small molecules that target structures on mRNA in an effort to block multiple oncogenes. She liked the science and the potential impact.

It was back to some of my earlier learnings, in terms of the right constellation of people around the table and the science that was ready for this very directed effort, she said.

So now she works from home, poring over the literature, directing CROs and her team of three, preparing for a fundraising round and building a whole team. Its a smaller company than she had led since she was just out of grad school, ignoring the pretensions of a sexist investor, and she couldnt be happier.

Its actually a lot of fun, she said. Jason Mast

Diana Brainard was studying abroad in France when she realized something just didnt quite feel right.

Intending to become a comparative literature professor while attending Brown, Brainard enrolled at a French university as part of her major and fully immersed herself for the first time in literature and lit theory classes. Brainard had mainly taken a balanced diet of courses stateside everything from math and science to English and the Study Abroad program was a necessary part of her program. She went into it head-on as her literature seminars were her favorite undergrad classes, with passionate professors seemingly putting on a production every class.

But after diving in, Brainard felt her studies had lost their attachments to the real world.

All of a sudden there was this realization of Wow, what Im really being assessed on in these classes, and how my career will be assessed in this field, is coming up with a theory and making that theory sexy, Brainard said. But that theory doesnt have to be true. It just has to be sexy and interesting and I can do all of that, but there is no truth here.

Since then, Brainard has moved past the days of Thomas Manns The Magic Mountain, though she hasnt lost her love of literature. Now, shes a senior executive at Gilead and has been a major part of the team that developed remdesivir, recently approved by the FDA as the first Covid-19 treatment for hospitalized patients.

The path from France to Gilead wasnt a straight line, however. Brainard notes that after Brown, she eventually went to med school expecting to become a physician. But that didnt end up being the right fit either, especially after Brainard fell in love with infectious diseases. She ended up as a researcher at Harvard focused on HIV, content to work off NIH-backed grants for the rest of her career.

Then biopharma came calling.

Leaving academics was really hard because I was happy doing what I was doing, and I hadnt envisioned in the future that I would be going to industry, Brainard said. There werent a lot of people at Harvard who had done that before, and so I felt like I was taking a big risk, I was leaving behind NIH funding, we were leaving Boston where wed been for a long time, and I didnt know if I would wind up regretting all of the things that I was letting go of.

Brainard jumped aboard first at Merck, then joined Gilead in 2010. Shes spent her entire career, in academia and otherwise, working in infectious diseases and immunology, and much of her time at Gilead has centered on hepatitis C treatments. When she was first alerted to remdesivirs potential benefits for a new coronavirus strain out of China almost a year ago, Brainard moved to get it into the lab as quickly and efficiently as possible.

Remdesivir was a team effort, Brainard said, and shes reluctant to take credit for spearheading the drugs pivot to Covid-19. Originally tested in hepatitis C and then Ebola, remdesivir showed early signs of in vitro activity in SARS and MERS. Brainard pushed for Gilead to begin a compassionate use program for the drug, and it received partial emergency authorization in May for severe Covid-19 cases.

That EUA was expanded in August to include moderate cases, and the FDA handed down a full approval in October for patients who have been hospitalized with the disease.

Its been exhilarating to do [this] for Covid because of the acute, unprecedented medical need, and because scientifically its fascinating to have a disease, as an infectious disease expert, to learn about a disease at the same time youre trying to figure out if a therapy for a disease works, Brainard said a few weeks before the approval. Its a really difficult problem, and one that doesnt come around very often.

The drug has received some pushback, as a study backed by the WHO found in mid-October that remdesivir had little to no effect in reducing mortality rates or the need for ventilators.

Though Brainard was originally hesitant to move from academia, shes happy to have found a home at Gilead and not have to deal with what she says are liabilities in that arena. She never really enjoyed the structure of how academic careers are traditionally judged, where the main goal is to work your way up the authorship ranks and get a couple of papers under your belt.

Brainard much prefers the collaborative environment in industry. And at Gilead, she thinks that collaboration helps her be a better role model for younger women rising through the field.

The impact that I have, a lot of it is the drugs, Brainard said, but a lot of it is the people. The people who I work with, a lot of the people who come to Gilead, for example, come right out of training and they make that transition in the same way that I did. Helping them learn how to think in this new environment and thrive, and flourish in a new environment, thats really meaningful to me. Max Gelman

Janice Chen is all about democratizing diagnostics.

The Mammoth Biosciences co-founder has made that her mission over the last three and a half years, working alongside newly-minted Nobel laureate Jennifer Doudna to develop diagnostic tools centered around CRISPRs gene editing techniques. But what might that look like in practice? Chen theorized some potential uses in a TEDx CERN Talk two years ago.

What if you could directly and accurately test for the flu at home? Chen said. What if you receive the prescription and treatment plan without having to step foot into a clinic? And what if the same principle could be applied to other dangerous diseases such as Ebola?

Chen kicked off her scientific career as an undergrad at Johns Hopkins, where she took a course in which students built the yeast genome from scratch. She credits that class with getting her the technical skills needed to apply to research and lab assistant positions, as well as explore how synthetic biology could lead to a swath of applications.

It also served as a jumping-off point for Chens ambitions, where she said she was able to get her hands wet in something with real-world applications rather than reading lines from a textbook. After a yearlong stint as a research technician at Harvard, where her work focused on Ralstonia eutropha bacteria, Chen moved on to her doctorate at UC Berkeley and joined Doudnas lab.

Its there where she first hooked on to CRISPR research.

Myself and colleagues in the lab, including co-founder Lucas Harrington, came across this unexpected finding that some of these Cas proteins were able to detect DNA, Chen told Endpoints News. A lot of it was serendipitous in terms discovering this activity, and being able to demonstrate it on real patient samples I think was really an exciting moment for me in thinking about OK, can we actually take this outside the academic lab and try to do something with it?

Though CRISPR has largely settled in the mainstream consciousness as a way to potentially cure a range of severe diseases along with the occasional headline that scientists are out to create gene-edited embryos in a lab Chen and the Mammoth team are looking at ways these tools can be used for disease detection. Instead of using the scissors normally associated with CRISPR to edit genes, Chen programs the tech to find a defined gene sequence and sends out a signal once its been located.

With the Covid-19 pandemic in full swing, Mammoth has also steered its research toward creating accessible and easy-to-use tests for the detection of SARS-CoV-2. In that instance, the platform is programmed with a guide RNA, and Chen hopes by working on tests that can function outside of the typical lab setting, this can be one of the ways to democratize the technology.

Its been successful because its programmable, Chen said. Theres a whole world of testing thats just starting to be closer to reality that has never quite been able to be done because of the limitations of infrastructure needs, the accuracy to actually be a viable solution. With CRISPR now on the scene, were really excited about the potential to address these point-of-need environments that dont rely on your traditional clinical laboratory.

Chen credits her doctoral advisors from Berkeley, Doudna included, with keeping her focused and transitioning from academia to becoming an entrepreneur at Mammoth. Ultimately, that led Chen to her north star of not just engineering new uses for CRISPR, but being able to create impactful technology in general.

(Doudna) herself is a serial entrepreneur, and so its been really important to have her mentorship, and seeing her as a role model being very successful in both the academic world as well as the startup world, Chen said, a few weeks before Doudna won the Nobel Prize.

As someone whos still in the early stages of her career, Chen recognizes the opportunity she has to make an impact on the women who follow in her footsteps. Shes already been named to Forbes 30 under 30 healthcare list from 2018 for being among the most influential millennials in the sector. By coincidence, all of her major research experiences from Johns Hopkins through Berkeley were led by women principal investigators.

And while Chen says theres not going to be one magic bullet that fixes everything in the industry, the best place to get started is by recruiting talent from all sorts of different backgrounds.

Once you have that talent and have them in the company its really important to ensure that they have the support systems and mentorship internally to help them grow, Chen said. Its important to recognize that there are really great leaders in companies that might not fit the traditional mold, and I think that there are a lot of companies that are starting to figure that out. Max Gelman

In a cramped, windowless lab basement beside Cambridges Blue Room bar, Ann Cheung stuck her head in the freezer and, with a vial of cells in one hand, used the other to phone a world-famous professor across town and a tech entrepreneur in San Francisco.

Cheung was 34. She had the academic pedigree: Brown, MIT, a postdoc at CalTech where she built nanoparticles and studied immunotherapy with a Nobel laureate. But it had been over four years since she worked with flasks and centrifuges. Her last job was at MIT but as an administrator and communicator. It involved a lot of tweeting.

Then a call came from Tyler Jacks, the renowned head of the MIT Center for Cancer Research (now called the Koch Institute) and her old doctoral advisor. Along with an old college friend, the Silicon Valley inventor Bill Haney, they wanted to bootstrap this new idea out of Jacks lab, a jackknife way of getting the immune system to turn on cancer. And Jacks knew Cheung was itching to get back to the bench.

Soon she found herself in the basement of a Kendall Square bar, in a lab no bigger than a university office, growing antibodies and natural killer cells with a single other employee and hearing the sounds of eating and loud talking whenever they went in the hall. She was the gritty and brilliant, if unlikely, CSO of Dragonfly Therapeutics, and her work there and in the shiny offices theyve since moved to would prove and develop ideas that eventually landed collaborations with Celgene, AbbVie and Bristol Myers Squibb. Last year, it entered patients for the first time.

Her growth has never stopped and this has been true for her entire career, Jacks told me. Theres no challenge that discourages her. Shes kind of fearless.

Cheung didnt arrive as a graduate student at Jacks MIT lab wanting to study immuno-oncology. This was 2002. Checkpoint inhibitors were still a fringe idea in the head of a wild-haired Berkeley professor. No one studied immuno-oncology in Jacks lab.

One evening, though, Bob Schreiber came in for a lecture. Schreibers mice work was just beginning to resurrect the idea of using T cells to attack tumors, and Cheung was captivated. On the walk back that night, she turned to Jacks with an epiphany. Of course the immune system can fight cancer, Cheung said. Cancer is something that is foreign to the body even though it comes from the body, so it absolutely makes sense.

Read more:
Special report: Twenty extraordinary women blazing trails in biopharma R&D Covid-19 and beyond - Endpoints News

Recommendation and review posted by Bethany Smith

Liz Tenety: I am Liz Tenety and I want to welcome you to The Motherly Podcast.

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Liz Tenety: So, as regular podcast listeners might know, I have four children and with three of those pregnancies, I experienced a condition called hyperemesis gravidarum, HG, which is horrible morning sickness. It's debilitating. It's just simply put like the hardest thing that I've ever gone through in my entire life.

And it's terrifying. I really never want to go through it again. For me, thankfully, it tends to let up around 20 weeks, but the first part of my pregnancy is unbelievably hard. I cannot get out of bed. I am vomiting constantly, even on medication. I can't do anything. I can't take care of my kids. I can barely work and I've had it with my first, my third and my fourth children.

Having HG is part of my story and it is one that has been incredibly humbling and scary, and almost every woman I know who has had a baby has some really hard thing that she's gone through, whether it's secondary infertility or HG or a genetic condition that gets diagnosed when she's pregnant. Finding out her baby is breech, having an unexpected C-section, postpartum depression We go through incredible hardships to bring babies into the world. And I don't think we talk about that enough. I don't think women get enough credit for being the heroes, the heroines that they are to endure this, to bring the next generation.

Liz Tenety: Hey mama. Welcome to the motherly podcast, honest conversations about modern motherhood. My name is Liz Tenety. I am the Co-founder of Motherly and I'm a mom of four myself. Today's interview is with Dr. Marlena Fejzo, a geneticist and the leading researcher on hyperemesis gravidarum. HG, as it's called for short, affects about 6 million women globally each year during pregnancy.

And it's characterized by severe nausea, vomiting, weight loss, dehydration, even sometimes organ failure. And in severe cases, it can lead to the death of mothers and babies. After experiencing HG herself and losing her baby to the condition Dr. Fejzo decided to devote her life to studying it. She's discovered two genes associated with hyperemesis gravidarum that has helped to shed a light on this little understood illness. In fact, her work has really changed the paradigm about what causes HG and this really debilitating condition for pregnant women. I actually experienced HG in three of my four pregnancies. So, I am so grateful for Dr. Fejzo's work.

Currently, Dr. Fejzo is a science advisor for the Hyperemesis Education and Fesearch Foundation called the HER Foundation for short. And that's the global voice for HG awareness research and support. Today it receives 200,000 visitors each year from around the world and they manage a global volunteer network with over 900 participants, all built to help women suffering from HG, find the resources and support they need.

I talked to Dr. Fejzo about her own experience with HG and how going through HG as a geneticist inspired her to do this kind of research and really lead the charge on understanding what the actual underlying causes of this debilitating condition. And we also talked about funding of women's health and how there is so little still understood about pregnancy and the changes that women go through biologically through their lives.

There are a lot of reasons why women's health has been historically underfunded and we get into it. Her work is incredible. I'm excited to share this conversation with you.

Dr. Marlena Fejzo, welcome to The Motherly Podcast.

Dr. Marlena Fejzo: Thank you for having me.

Liz Tenety: So, I know we just met, but you are one of my favorite people on the planet. I have been diving into your incredible research, your work on hyperemesis gravidarum known as HG and as a woman who has suffered from HG three times, like I cannot get enough of learning about what you are discovering.

And I can't wait to talk about all of that. So, can you actually define what hyperemesis gravidarum is and what are the symptoms that women should be looking out for?

Dr. Marlena Fejzo: So, hyperemesis gravidarum is nausea and vomiting. That's severe enough to affect your daily routine and to affect your intake so that you're not able to eat or drink properly. And that leads to weight loss. Usually it's diagnosed when you have more than 5% of body weight loss and electrolyte disturbances for not being able to drink or eat properly.

Liz Tenety: So, can you tell our listeners a bit about your own personal story and why you decided to devote your life to not only studying HG, but a lot of critical topics in women's health?

Dr. Marlena Fejzo: I did my PhD in genetics and women's health. My PhD was from Harvard on uterine fibroid tumors, which are also a big problem for women. And, you know, there's not as many female scientists as male scientists. And so, for me, it was very important to focus on women's problems. You know, there's plenty of scientists working on male problems and not very many working on female problems.

And then I went on then I had HG during my post-doc and then had it again. In my second pregnancy, I had a really, really, very severe HG pregnancy. My second pregnancy, the baby died in the second trimester because I was so ill. I didn't keep anything down for 10 weeks and I couldn't move without vomiting. I got so weak. I couldn't speak. I had to have a buzzer to signal when I needed a bed pan change or a medication change. I basically could not move for weeks and weeks. And finally, the baby died. And I decided to look into what was known about HG and there was so little known that I decided, I'm a scientist and I've got to devote my life to figuring this out.

Liz Tenety: There's so much you've already said that is so powerful. And I know our listeners can't see us, but I'm tearing up hearing it because there aren't words to describe what you go through with HG. That was part of this conversation as I was imagining it, I can't tell you what it's like to go through that, but you described in your particular case, you literally could not move your body. It was the most dark time of my life to go through those three pregnancies.

And yet, you have led a body of research into the evidence of what is actually happening inside women's bodies. When they experience HG, what was believed about the cause of HG before, you know, there was this new wave of research and understanding.

Dr. Marlena Fejzo: Yeah. So, that's the terrible thing, since it's a women's problem. And on top of that, a women's problem during pregnancy, and there's sort of always, you know, you see it still in the movies and on TV that there's this idea that pregnant women are hysterical or irrational. And so, that perpetuates this idea that it was all in a woman's head and over time, there were theories that really got picked up that it was a subconscious rejection of their pregnancy that they didn't want to be pregnant and all kinds of irrational theories that are just not scientific and not true.

Liz Tenety: So, what is the difference between morning sickness as we know it and what do we believe morning sickness like what is the purpose of morning sickness and what is the difference between that and HG?

Dr. Marlena Fejzo: No one really knows for sure, but we can guess that morning sickness has evolved as a way to avoid foodst hat would be dangerous. When the fetus is developing, when all the organs are developing and you don't want to ingest anything that could affect that.

And so, what comes with morning sickness is this increased sense of smell and taste. And so, those are generally thought as a way that has evolved to protect the fetus. With HG, it's just morning sickness out of control.

Liz Tenety: I kind of had heard from my doctor when I first had HG with my first child, she seemed to think it was in my stomach, that the problem was happening in my stomach. And it was about eating crackers and always having something in my belly. These were the ideas that I was being told to start to remedy it. But your research is showing that it's actually happening in the brain, or it's at least this cycle of feedback that is neurological.

Dr. Marlena Fejzo: Exactly. So, since I'm a geneticist, I decided to look first into seeing whether it was genetic. I don't have it in my family, but I decided to look into it. And what I found was that. There was a lot of evidence that it's genetic, there's a 17-fold, increased risk of having it if your sister has it. And twin studies where they compare the genes and the chance of getting hyperemesis in identical twins versus fraternal twins have shown that it is highly heritable.

So, there's a lot of evidence that it's genetic. There's 70% heritability. What I then did was to embark on a genetic study and I partnered with the personal genetics company, 23andme and we scanned over 15 million genetic variance in over 50,000 women that did not have HG compared to 1300 women that were hospitalized with HG.

And so, we compare their DNA at these variants and we found very significant differences in their DNA around this hormone called GDF 15. And that hormone is turned on in the placenta. It's expressed very highly in pregnancy. A lot of doctors thought that it was caused by a pregnancy hormone, if they didn't believe the psychological theory, but we found no evidence to support GDF 15 as being the causal hormone. We found very strong evidence for it being this hormone, GDF 15.

Then I went on to see, okay, so it's genetically associated, but what about the actual hormone itself and confirmed that there are significantly higher levels of this hormone in the blood in women with HG compared to women without HG. And then, recently the receptor for this hormone was found by other groups and the receptor, which is what the hormone binds in the brain that causes this nausea and vomiting and loss of appetite and change in taste, it goes up travels through the bloodstream. It goes into the brain, binds this receptor, and then causes this nausea and vomiting. And that can get out of control because if you already have this predisposition to have higher levels, you're going to vomit more than normal. You're going to have nutrient deficiencies, which lead to another further increase in the levels of GDF 15 and you get this downward spiral to hyperemesis gravidarum.

Liz Tenety: And those nutritional deficiencies that mothers get when they have HG, lead to, you know, negative impacts on the fetus, including much higher rates of autism.

Dr. Marlena Fejzo: Yeah. So, there is, I wouldn't say much higher I don't want to scare women, but there is an increased risk for neurodevelopmental delay.

There's an increased risk for autism, you know, speech, delay, language disorders, different kinds of neurodevelopmental disorders. And, you know, long-term outcomes in the mother, as well as the child. So, it used to always be thought that, you know, don't worry about what you get. The baby's getting everything it needs from mom, but in the case of HG, that is just not true.

Liz Tenety: That is literally what my doctor told me. And that child, that first pregnancy we have had diagnoses along those lines. So, you know, I can't say for sure, but I am living your research every day. I wonder when you're doing your work, you brought up how women's health and maternal health for a number of reasons has not been as much of a focus of the scientific community as the health and wellness of men.

Do you feel excited about being a pioneer in this field, or do you feel frustrated that we've had women as long as we've had human beings and we still don't know some of the basic things of how our bodies work, because we haven't invested in this kind of research?

Dr. Marlena Fejzo: That's a good question. I would say I have days of both there's days where I'm really excited and so happy that we're making progress, but the progress is so slow. We need other people following my path. The fact that I am a world-renowned researcher in this field is not really because I'm so great. It's because there's barely anybody else. It does definitely bother me that there's so little research out there and that it's going so slowly and that, you know, I still hear stories of women being mistreated with this disease.

And I've been out there publishing for 20 years to try to change that. So, I definitely do feel frustration often, but yes, I'm very excited that we finally made some progress and hopefully we can change things. And a lot of people don't know about my research. And so, it's really important to get the word out and spread the word

Liz Tenety: As a result of your research, finding that there is DNA in certain women, that you will have particular genetics that lead to this cycle, and you have HGit will lead to a different kind of treatment. Is that right? Where are you in that process of now that we understand HG, what do we do about it?

Dr. Marlena Fejzo: Yeah. So, it's a pretty new finding and the fact that this is a hormone and the identification of the receptor for it are pretty new. So, we have a ways to go to understand how this all works, but we are hopeful that there will be medications that will be used to block this pathway so that we can actually have something that works to treat HG. The interesting thing about this hormone is that it also is involved in cancer.

Cachexia is basically when you can no longer eat, when you have cancer. And it kills about 20% of cancer patients. And just like GDF 15 is overexpressed by the placenta, it's also overexpressed in some cancers. And so, those patients that have high levels of GDF 15 turned on in their cancers also have this appetite loss muscle wasting and they ended up many of them dying from it.

When women say they feel like they're dying from HG, often people do not believe them. They say they're exaggerating. But the actual levels of GDF 15 in women that are pregnant and have HG is the same, or sometimes even higher than people that are dying from cachexia.

Liz Tenety: I'm getting choked up again because that's what it feels like. But I think people may not realize too, when you have HG, it doesn't just affect you when you're pregnant. I mean, it affects, of course, the experience. But many women decide to terminate these wanted pregnancies because they cannot endure what they're going through. Some women have PTSD. And even though it's a small segment of women, it is very traumatic and some very prominent women, Amy Schumer, Kate Middleton have gone through it. But like you said, we're just starting to wrap our heads around how overwhelming and how misunderstood this condition has been.

Dr. Marlena Fejzo: Yes, it is overwhelming, misunderstood, and it has long-term effects for the mom and it can have long-term effects for the child.

Liz Tenety: There are other considerations when it comes to reasons why this kind of research hasn't has not happened. One of them is that there was a medication in the 20th century that negatively affected a lot of women and children. There are other ethical considerations with pregnancy. So, how do you navigate that in your own research and understanding.

Dr. Marlena Fejzo: Yeah. So, there was a drug that was given in the fifties to women for HG in Europe. And it ended up causing birth defects, limb deformities. And so, unfortunately, that has caused pharmaceutical companies and doctors and patients themselves to be scared to develop, to treat patients and to take medications in pregnancy.

I think that the tide is starting to change. With that, as you know, we're starting to understand that some medications can be safe in pregnancy and, you know, we have to go slowly to make sure that I don't know if a GDF 15 inhibitor is going to be safe in pregnancy, but we're going to have to try.

And the fact that there can be long-term outcomes to the child if they don't take medication, has to be weighed against the possible risks.

Liz Tenety: Thrilled to hear that the tide is turning. If a woman is experiencing this and she's going to go to her doctor or her midwife, and just say, I am, I'm just so sick. How does she know how to flag that this is not normal morning sickness? That this is a severe condition that requires a different level of intervention.

Dr. Marlena Fejzo: Exactly. So that's why we developed our HG care app so that women could know, because especially in their first pregnancy, a lot of women don't know, and they haven't seen a doctor yet when the symptoms start.

And so, they can be missed before it's too late. There was actually a woman that died just in August. She was only nine weeks pregnant, so it's very important for women to know what the symptoms are and what is normal. And I feel like every woman should be screened immediately when they're first pregnant for this, because right now, a lot of women only go to the doctor and have had their first appointment pretty late after symptoms of HG can already get severe.

So, our app has alerts to tell you when you need to talk to your doctor, but generally if you're getting dehydrated, then it's time to see your doctor. If you're not able to eat, if you're not able to drink, you're not able to do your normal daily routine and you're losing weight, you're actively losing weight. Then you need to talk to your doctor about possibly having HG. There is a test where you can pull up your skin on the back of your hand, and normally it should bounce right back. If it goes back slowly, then that means you're dehydrated. And you need to get hydrated.

Liz Tenety: I want to talk a bit about the foundation. Can you tell me about it?

Dr. Marlena Fejzo: So, basically the way it happened was after my HG nightmare, I realized there was so little known and I put out a survey with my brother. He helped me. He's a statistician. And we put out a survey on the internet about HG and put in questions about it that I wanted to know the answers to. And one of the women that answered that survey faxed back her answers and that was Kimber McGiven and she was a nurse who was going through HG and she said, I'm so sick now, but I was so happy to find your survey. She wrote on her survey, as soon as I'm done with this pregnancy, I'm going to make a website. And so, she made a website on HG and she's amazing.

She's been working for years on this, only recently giving her itself a tiny salary, but she's just devoted all her time with no pay to do this. And she has an amazing website. And then she got joined by another couple that had gone through a horrible HG pregnancy and they then created the foundation: The HER Foundation. And so the webpage is hyperemesis.org and I'm a science advisor for them. And I'm on the board.

Liz Tenety: What is the current best evidence-based treatment for HG? And what can those around a woman going through HG do, if anything, to relieve any of her suffering?

Dr. Marlena Fejzo: So, we did research on what women found to be the most effective treatment. So, I'm basing my answer on that, which is that on Dantron or Zofran was the most effective treatment for women in our study for helping to lessen the, the vomiting. It doesn't necessarily help that much with the nausea in all women, but it does lessen the vomiting in more women than any other medication reported except for possibly steroids.

But doctors often do not give steroids to women because there are some possible safety concerns. So, that's from our study. But unfortunately, even on Zofran, it's reportedly only effective in maybe 50% of women. So, we definitely still need something better.

To answer your second question, what can we tell the families, women with HG need a lot of support? They need an advocate. When you're feeling nauseous, you cannot advocate for yourself. So, they need someone to go with them. To doctor's appointments and and to speak for how ill they are. When a woman is ill and feeling like they're about to throw up, they're not going to speak out to their doctor when their doctor says something that they don't agree with.

Like, oh, just take crackers. So, women need to have either a family member or friend go to the doctor and explain.

Liz Tenety: And yet, like you said, I mean, I literally heard from my doctors, the baby's a parasite and the baby will take everything that the baby needs, but your research has shown that that's just, that's just not true.

Why is it that there's so much conventional wisdom that isn't evidence-based that is still out there in modern medicine, especially as a relates to women?

Dr. Marlena Fejzo: I think it's really hard to get the word out and that these ideas are passed on then medical books and the medical schools. They're teaching the next generation of doctors, the same things that they learned and not updating it.

So, I've heard of this year, a doctor teaching her medical students. (One of them had HG. So, she's the one who told us about this.) She was teaching her medical students, that women, they're sometimes hospitalized, and they just don't want to get better. That's what she told this next generation of doctors in a class. Women just don't want to get better.

This was a female doctor teacher teaching her next generation of students. So, if they're learning that from someone that they trust to teach them the facts, then that's what's happening. And so somehow that has to change and we have to just get the word out the best we can.

Liz Tenety: What are the other big topics in women's health and maternal health that we don't know enough about?

Dr. Marlena Fejzo: There's menopause, lupus that occurs more in women, many, many women's issues. And just having your period and the medications to help with cramps, you know.

Liz Tenety: Well, it seems like being a woman is the qualifying factor, because if its periods to menopause, that covers a lot of our lives that we may not know as much about as we should.

Dr. Marlena Fejzo: One thing you asked me before about, you know, am I excited or am I I don't mean to be only negative because we are making progress and things are slowly changing. But one of the things that I was really upset about that really got me riled up was that the national Institute of health funded a genome-wide association study, which is the same type of study that I did with 23andMe, because I couldn't get funding from the NIH.

They funded a study on erectile dysfunction. Erectile dysfunction, first of all, is not nearly as heritable. There's not as much genetic evidence to support that it is genetic compared to hyperemesis and other women's issues.

And yet they funded that. In addition, with erectile dysfunction, there are millions of dollars, billions of dollars spent on it by drug companies by the government. That was really frustrating to me. Erectile dysfunction is bad too, but when you compare it to HG, that's affecting the mother and the child. I don't think you can compare it. And so, it's just an example of money being spent on male issues and not female issues.

Liz Tenety: After you lost your baby at 15 weeks through that experience you had with HG, you did go on to have other children. How did you navigate the decision to have more children? And I know you ended up working with a surrogate. So, what was that like? Tell us about that.

Dr. Marlena Fejzo: Yeah, so having a surrogate was never something that was on my radar, especially back then. There were very few people that did that.

Liz Tenety: What year was that?

Dr. Marlena Fejzo: That was back in 1999. It was something that my OB suggested to me that I was a good candidate for. And after I lost the baby, you know, I had one child and I come from a big family. I have two brothers and a sister, and I always wanted a big family too. So, it was going to be either surrogacy or adoption for me. I was not going to go through HG again.

Liz Tenety: Do you see those experiences as different motherhood's or is there a theme in how you've bonded with those children in the same way or in a different way? How do you see that?

Dr. Marlena Fejzo: I think it was the same as far as, you know, giving birth and having the surrogate. I was able to watch her give birth to my babies, and I really consider her my angel for doing that for me. And both ways are miracles, you know, giving birth to a child is a miracle, but having someone else do that for you is also such an amazing miracle.

Liz Tenety: Do you feel that the loss of your child that you did experience is a source of motivation or meaning in your ongoing research and advocacy for HG?

Dr. Marlena Fejzo: Definitely. I mean, that is what keeps me going. I don't want that to happen to anybody else. I know it's still happening to women and it's very sad for me when I, you know, women write me and tell me they've gone through that. It's very sad and frustrating to me because I've been working on this for 20 years and to see that women are still going through this and I hope that it's going to change. And I hope that we're going to find a medication that works and stops that. But yeah, definitely. And I don't want to see my daughters go through it either, of course. So, that will be devastating to me if they have to go through that.

Liz Tenety: Okay. So, at Motherly, we believe that motherhood brings out our superpowers and to me, a superpower is something unique, a strength perhaps within you that maybe you didn't even know was there before you became a mom. So, I wonder what you think is your superpower.

Dr. Marlena Fejzo: Patience. I would say patience is really important as a mother and as a scientist. Patience and trudging slowly on. There have been many, many setbacks in my research and just getting up and go forward again. Being patient. We're getting there. But yeah, with kids too. You need patience.

Liz Tenety: I love that. Well, Dr. Marlena Fejzo, thank you so much for sharing your story and your research with baths on The Motherly Podcast.

Dr. Marlena Fejzo: Thank you for having me.

Liz Tenety: Now for a quick word, from this episode's sponsor ThirdLove. Motherhood is one of the most amazing and transformational experiences a woman can have. It's about feeling the joy of bringing this new little person into the worlds and learning how to be comfortable in our own skin, finding a new routine and owning our new confidence.

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Liz Tenety: When I'm pregnant, do you remember what happens to me at the beginning of most of my pregnancies? What happens when I get really sick?

Henry: You start to throwing up like three times, each day, three to 10 times each day.

Liz Tenety: Yeah. It's like 10 to 15 times a day. Yes, you're totally right. If you remember, I just basically stayed in bed for three months. Do you remember that part?

Grant: How'd you eat?

Liz Tenety: I couldn't eat

Grant: But then you wouldn't be able to survive.

Liz Tenety: I just get the tiniest amounts of food and water. And sometimes they put the IVs in my arms to get me fluid. But you know, I was like that with you, Henry. But with Grant, I didn't get really sick, but so with three of the kids pregnancies, I got super, super sick, but one kid and I'm looking at him, he did not make me throw up 10 times a day. Good job, Grant!

Grant: Because I'm so disgusting.

Liz Tenety: Oh, is that it? Because you are so disgusting, that's why I didn't throw up?

Grant: Hmmhmmm.

Liz Tenety: Well, that's it for our show this week. I can't thank you enough, Dr. Fejzo for your time and for your work.

And I also want to thank our listeners for listening to our podcast. This season, we have an incredible lineup coming in 2021. I can't wait for you to listen. And as always, we would love it if you spread the word about The Motherly Podcast.

So, if you can leave us a review on Apple podcasts, it takes 30 seconds max, and it really helps other mamas discover our show.

The Motherly Podcast is produced by Jennifer Bassett with editing from Seaplane Armada. Our music is from the blue dot sessions and I am your host, Liz Tenety. Thank you so much for listening.

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Hyperemesis Gravidarum researcher Dr. Marlena Fejzo is on a mission to understand women's health - Motherly Inc.

Recommendation and review posted by Bethany Smith

The Telegraph

Australia has cancelled the production of a locally made Covid-19 vaccine after trial volunteers falsely tested positive for HIV, meaning the drug could interfere with diagnosis of that virus. Antibodies generated by the jabs developed by the University of Queensland (UQ) and biotech firm CSL led to trial subjects wrongly testing positive for the virus that causes AIDS. Further trials have been stopped. Scientists said the results were a blow to Australia's vaccine development and was likely to force the country to buy more doses of imported shots. "While this is a tough decision to take, the urgent need for a vaccine has to be everyone's priority," said UQ professor Paul Young. Australia has ordered a total of 140 million shots from different suppliers, to inoculate its 25 million people, making it one of the most highly stocked countries in the world. "We want to ensure that Australians ... have full confidence, absolute full confidence that when it gets the tick, they can get the jab, and they can make that decision for themselves and for their families, confidently, said Scott Morrison, prime minister. Prof Sarah Palmer, from the faculty of medicine at the University of Sydney, said: Sadly, this is a set-back for the development of Covid-19 vaccines. Generating a false positive for HIV is entirely unexpected for this vaccine, but underscores the critical necessity of testing the safety of newly-developed vaccines in large numbers of volunteers. She said the Australian government, which was a major backer of the UQ vaccine effort, would have to consider funding other alternatives, including imported vaccine from firms such as Pfizer and Moderna. Australia's strict quarantine regime has seen the country quash earlier outbreaks and its tally of 28,000 infections is far fewer than in many other developed countries Its success in keeping a lid on infections has meant the country is not racing to start vaccinations like countries in Europe and jabs are not scheduled to begin until March. CSL, had been under a contract to produce 51 million doses of the UQ vaccine, and will instead produce an extra 20 million doses of the Oxford vaccine being developed with Britain's AstraZeneca.

See the original post:
Loeffler claims she is the candidate who will create jobs - Yahoo News

Recommendation and review posted by Bethany Smith

SHANGHAI, China, Dec. 09, 2020 (GLOBE NEWSWIRE) -- Everest Medicines (HKEX 1952.HK), a biopharmaceutical company focused on developing and commercializing transformative pharmaceutical products that address critical unmet medical needs for patients in Greater China and other parts of Asia, today announced that the first patient has been dosed in the Phase 3 registration Asian study EVER-132-002 evaluating TrodelvyTM (sacituzumab govitecan) versus treatment of physicians choice (TPC) in subjects with hormonal receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2) metastatic breast cancer (mBC).

EVER-132-002 is a Phase 3 Asian study designed to assess and compare the efficacy and safety of sacituzumab govitecan versus TPC in Asian patients with HR+/HER2- mBC who received at least two, and no more than four systemic chemotherapy regimens. The trial will enroll up to 330 HR+/HER2- mBC patients in China mainland, Taiwan and South Korea. The primary endpoint is progression free survival (PFS) per RECIST v1.1 by an Independent Review Committee.

HR+/HER2- breast cancer is the most prevalent subtype of breast cancer and accounts for more than 60% of all breast cancer cases. There is a significant unmet need for new treatment options for women with HR+/HER2 mBC who have failed initial standard-of-care chemotherapies, said Dr. Yang Shi, Chief Medical Officerfor Oncology at Everest Medicines. The clinical data generated to date suggested promising clinical activity of sacituzumab govitecan in HR+/HER2 mBC patients who have failed at least two chemotherapy regimens. We are very excited to initiate our Phase 3 registration trial as we believe sacituzumab govitecan has tremendous potential to become the new standard of care in patients with pre-treated HR+/HER2 mBC.

Immunomedics (now part of Gilead Sciences, Inc), which developed sacituzumab govitecan, is currently recruiting patients for the TROPiCS-02 trial, an open-label, randomized, multi-center Phase 3 study to compare the efficacy and safety of sacituzumab govitecan versus the TPC in subjects with metastatic or locally recurrent inoperable HR+/HER2- mBC, after failure of at least two, and no more than four, prior chemotherapy regimens for metastatic disease.

About Sacituzumab Govitecan

Sacituzumab govitecan is a first-in-class antibody-drug conjugate (ADC) directed at TROP-2, a membrane antigen that is over-expressed in many common epithelial cancers. Sacituzumab govitecan was granted accelerated approval by the U.S. FDA in April 2020 for the treatment of patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. In September 2020 at the ESMO2020 annual conference, Immunomedics (now part of Gilead Sciences, Inc.) presented the confirmatory Phase 3 trial results (ASCENT) demonstrating that sacituzumab govitecan significantly improved progression free survival (PFS) and overall survival (OS) over standard single agent chemotherapy in pre-treated metastatic triple-negative breast cancer (mTNBC) patients with a hazard ratio of 0.41 and 0.48 respectively. Under a licensing agreement with Immunomedics, Everest Medicines has exclusive rights to develop, register, and commercialize sacituzumab govitecan for all cancer indications in Greater China, South Korea, and certain Southeast Asian countries.

In October 2020, sacituzumab govitecan was included in the updated 2020 Guidelines for the Standardized Diagnosis and Treatment of Advanced Breast Cancer in China, compiled by the Breast Cancer Expert Committee of the National Cancer Control Center, the Breast Cancer Professional Committee of the Chinese Anti-Cancer Association, and the Cancer Drug Clinical Research Professional Committee of the Chinese Anti-Cancer Association.

About HR+/HER2- Breast Cancer

Hormone Receptor Positive, HER2 Negative (HR+/HER2-) breast cancer is the most common form of breast cancer in China, representing over 60% of all breast cancer cases. This subtype of breast cancer grows in connection with estrogen or progesteroneand is likely to respond to hormone therapies initially, but almost all HR+/HER2- metastatic breast cancers becomerefractory over time.

About Everest Medicines

Everest Medicines is a biopharmaceutical company focused on developing and commercializing transformative pharmaceutical products that address critical unmet medical needs for patients in Greater China and other Asian markets. The management team of Everest Medicines has deep expertise and an extensive track record of high-quality clinical development, regulatory affairs, CMC, business development and operations both in China and with leading global pharmaceutical companies. Everest Medicines has built a portfolio of eight potentially global first-in-class or best-in-class molecules, many of which are in late stage clinical development. The Companys therapeutic areas of interest include oncology, autoimmune disorders, cardio-renal diseases and infectious diseases. Everest Medicines obtained the development and commercial right in greater China, South Korea and certain Southeast Asian countries of sacituzumab govitecan from Immunomedics in April 2019. For more information, please visit its website at http://www.everestmedicines.com.

Everest MedicinesMedia in US and Europe: Darcie RobinsonVice PresidentWestwicke PR(203) 919-7905darcie.robinson@icrinc.com

Media in China: Edmond LococoManaging DirectorICR Asia+86 (10) 6583-7510edmond.lococo@icrinc.com

Originally posted here:
Everest Medicines Announces First Patient Dosed in Phase 3 Registration Asian Study of TrodelvyTM (sacituzumab govitecan) for Hormone Receptor...

Recommendation and review posted by Bethany Smith

It may be possible for some postmenopausal women to avoid some breast cancer treatment without compromising survival, according to two new studies presented at the San Antonio Breast Cancer Symposium (SABCS), hosted by UT Health San Antonio, the American Association for Cancer Research, and the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine.

The meeting was held virtually December 8 to 11.

One study found that postmenopausal women with early-stage breast cancer who were at low risk of recurrence can skip chemotherapy after surgery. The other found that older patients may be able to skip radiation therapy following breast-conserving surgery.

The studies reflect a resolve in the oncology field to avoid overtreatment of disease, sparing patients from some of the side effects that can accompany treatments like chemotherapy and radiation.

Were looking to move beyond a one-size-fits-all approach, said the presenting author of the first study, Kevin Kalinsky, MD, director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University. This is another step forward in trying to achieve precision medicine.

Dr. Kalinskys study followed women with hormone receptor-positive (HR positive), HER2-negative breast cancer the most common form of breast cancer for about five years following treatment.

The 5,083 study participants had early-stage lymph node-positive cancer (meaning the cancer had spread to one to three lymph nodes) and a recurrence score of 25 or lower.

Breast cancer recurrence scores are based on the presence of 16 cancer-related genes and can range from 0 to 100.

All the study participants received endocrine therapy following surgery, while about half were randomly assigned to receive chemotherapy as well.

The study, which was organized by the SWOG Cancer Research Network and is called RxPONDER, found that while additional chemotherapy improved disease-free survival rates by about 5 percent for premenopausal women, postmenopausal patients gained no added benefit.

This will save tens of thousands of women the time, expense, and potentially harmful side effects that can be associated with chemo infusions, Kalinsky said.

Questions remain about whether chemotherapy has different biological effects based on menopausal status, or simply exerts its effect by shutting down ovarian function.

In the second study, known as PRIME II, researchers found that older patients with HR-positive breast cancer may be able to skip radiation treatment after breast-conserving surgery.

The study enrolled 1,326 women ages 65 and older who had HR-positive breast cancer that had not spread. All of the women had breast-conserving surgery and received hormone therapy. Half of the study participants were assigned to also receive radiation therapy after surgery.

Previous research has suggested a higher risk of cancer recurrence among patients who do not receive radiation therapy. However, the new study found no significant differences in survival, metastasis (disease spread), or new breast cancers among the two groups after five years of follow-up.

The study is important because many postmenopausal women are diagnosed with less-aggressive breast cancers but still receive whole-breast radiation therapy following breast-conserving surgery.

Over half the patients diagnosed with breast cancer in developed countries are over the age of 65 years, said Ian Kunkler, MBBCh, a professor of clinical oncology at the Western General Hospital at the University of Edinburgh in Scotland. We were interested in determining whether older patients with low-risk breast cancer could be spared radiation therapy.

We found that omitting postoperative radiation therapy did not compromise survival or increase the risk of distant metastasis, Dr. Kunkler said. Based on these results, we believe that omission of radiation therapy after breast-conserving surgery should be an option for older patients with localized, HR-positive breast cancer who are receiving adjuvant hormone therapy and meet certain clinico-pathological criteria.

The study findings may not be applicable to patients with high-grade tumors or tumors larger than 3 centimeters, he said, because there were only a few patients with grade-three tumors in the study.

RELATED: Everyday Healths Building a Breast Cancer Community Twitter Chat: Heres What You Missed

A fresh analysis of the landmark phase 3 monarchE clinical trial showed adding Verzenio (abemaciclib) to endocrine therapy significantly benefits patients with high-risk, lymph-node positive, early-stage breast cancer thats classified as HR-positive, HER2-negative.

Many patients with HR-positive, HER2-negative early-stage disease will not experience a recurrence of cancer with endocrine therapy alone, said the study presenter, Priya Rastogi, MD, associate professor in the department of medicine at the University of Pittsburgh and medical director of the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation.

But about 20 percent of patients will experience a recurrence of the disease within 10 years of their initial diagnosis. These recurrences are typically diagnosed as incurable metastatic breast cancer, she said.

An earlier release of data from the trial, which includes 5,637 patients, showed the addition of Verzenio to endocrine therapy curbed the risk of invasive disease recurrent by about 25 percent. The new data, which followed patients for longer, showed that those who received Verzenio experienced a 28.7 percent reduced risk of invasive disease.

Since some women experience relapse several years after their initial treatment, it will be important to gather long-term data on the treatment regimen, said SABCS codirector C. Kent Osborne, MD, professor in the department of medicine, hematology, and oncology at Baylor College of Medicine in Houston. Dr. Osborne was not involved in the study.

The study will continue with a longer-term assessment of overall survival rates among the two groups.

RELATED: New Treatment for Aggressive Breast Cancer Announced at ESMO 2020

Women with breast cancer who undergo radiation therapy may have side effects that go unreported or unnoticed by healthcare providers, according to a study from the University of Michigan.

The study was comprised of 9,868 patients with breast cancer who were treated with radiation therapy. Researchers compared the patients reports of side effects with those assessed by their physicians.

The study showed physicians tended to under-recognize pain severity as well as itching (pruritus), swelling, and fatigue. Among the 5,510 patients who reported at least one substantial symptom during radiation therapy, 53.2 percent had under-recognition of at least one of the four symptoms.

Recognition of symptoms is necessary for appropriate supportive care, said Reshma Jagsi, MD, DPhil, the Newman Family Professor and deputy chair of the department of radiation oncology and director of the Center for Bioethics and Social Sciences in Medicine at the University of Michigan in Ann Arbor.

This work reveals that [physicians] systematically miss substantial symptoms in certain patients, including patients who are younger or of Black or other race.

The study points to the need for physicians to improve the way they assess side effects in patients, said SABCS codirector Virginia Kaklamani, MD, a professor of medicine in the division of hematology and medical oncology, University of Texas Health Sciences Center in San Antonio. Dr. Kaklamani was not involved in the study.

Its really quite surprising to me that in 30 percent of cases there was under-recognition compared to what patients are reporting, she said. We need to do a better job.

I think the key here is improving physician-patient communication, she said. That involves a spectrum of potential interventions which begins with addressing our own unintentional biases.

RELATED: Closing the Gap in Breast Cancer Care and Support for Black Women

Read the original post:
Less Treatment May Be Fine for Some Women With Breast Cancer - Everyday Health

Recommendation and review posted by Bethany Smith

Sara M. Tolaney, MD, MPH, discusses where she sees the treatment landscape evolving in the future for the treatment of patients with hormone receptor-positive metastatic breast cancer.

Sara M. Tolaney, MD, MPH, associate director of the Susan F. Smith Center for Womens Cancers; director of Clinical Trials, Breast Oncology; and senior physician at Dana-Farber Cancer Institute, and assistant professor of medicine at Harvard Medical School, discusses where she sees the treatment landscape evolving in the future for patients with hormone receptor (HR)-positive metastatic breast cancer.

There have been many advancements over the last several years for the treatment of patients with HR-positive metastatic breast cancer, but Tolaney believes there will be a shift towards combination therapy in the future. Current treatment options in the include the combination of endocrine therapy with CDK4/6 inhibition, while physicians may also consider mTOR or PI3K inhibition with endocrine therapy.

In terms of moving forward, Tolaney says 1 major consideration will be combination strategy, which is under exploration in several clinical trials today. These studies are aiming to move the use of CDK4/6 inhibition forward, as well as treatments in the adjuvant setting and treatment with mTOR and PI3K inhibitors as partners for combination strategies. Tolaney says there are many options and new directions for replacing endocrine therapy backbones and perhaps moving into the earlier disease settings. However, first robust data from monotherapy trials are needed.

Continued here:
Combination Strategy May Play Role in Treatment of HR+ Metastatic Breast Cancer - Targeted Oncology

Recommendation and review posted by Bethany Smith

This activity offers CE credits for:

1. Physicians (CME)

2. Other

All other clinicians either will receive a CME Attendance Certificate or may choose any of the types of CE credit being offered.

ACTIVITY GOAL

The goal of this activity is to inform readers about the possible connections between infertility and mental health disorders.

LEARNING OBJECTIVES:

Understand the prevalence of mood and anxiety disorders in women experiencing infertility and undergoing infertility treatment

Identify patients who may need psychiatric support during infertility treatment

Appreciate factors that may modulate vulnerability to stress, anxiety, and depression in the context of infertility and its treatment

Identify appropriate treatment options for mood and anxiety disorders in women undergoing infertility treatment

TARGET AUDIENCE

This continuing medical education (CME) activity is intended for psychiatrists, psychologists, primary care physicians, physician assistants, nurse practitioners, and other health care professionals who seek to improve the care of patients with mental health disorders.

ACCREDITATION/CREDIT DESIGNATION/FINANCIAL SUPPORT

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Physicians Education Resource, LLC and Psychiatric TimesTM. Physicians Education Resource, LLC is accredited by ACCME to provide continuing medical education for physicians.

Physicians Education Resource, LLC designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

This activity is funded entirely by Physicians Education Resource, LLC. No commercial support was received.

OFF-LABEL DISCLOSURE/DISCLAIMER

This CME activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME activity is for continuing medical education purposes only and is not meant to substitute for the independent clinical judgment of a physician relative to diagnostic or treatment options for a specific patients medical condition.

The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of Physicians Education Resource, LLC.

FACULTY, STAFF, AND PLANNERS DISCLOSURES

Elizabeth Clayton, Ruta Nonacs, MD, PhD, Linda L.M. Worley, MD, FACLP (external reviewer), the staff members of Physicians Education Resource, LLC, and Psychiatric TimesTM have no relevant financial relationships with commercial interests.

HOW TO CLAIM CREDIT

Once you have read the article, please use the following URL to evaluate and request credit https://education.gotoper.com/activity/ptcme20dec. If you do not already have an account with PER you will be prompted to create one. You must have an account to evaluate and request credit for this activity.

Ms Clayton is an MD candidate (class of 2021) at Tufts University School of Medicine. Dr Nonacs is clinical assistant professor in the Department of Psychiatry at Massachusetts General Hospital and editor in chief at the MGH Center for Womens Mental Health.

Difficulty with conceiving can have many psychological repercussions. Infertility is defined as the inability of a couple to conceive after 12 months of regular intercourse without the use of contraception in women aged 35 years or younger, or after 6 months in women aged 36 years or older. The Centers for Disease Control and Prevention (CDC) reports that 12% of women aged 15 to 44 years have difficulty getting pregnant or carrying a pregnancy to term (Figure). Some form of infertility was reported by 9% of men aged 25 to 44 years. In about 35% of couples surveyed, infertility was due to both male and female factors.1

Infertility can have a profound impact on psychological well-being for both the individual and the couple. A woman may find herself feeling betrayed by her body and may be overcome by emotions, ranging from profound despair to anger and resentment, when a friend announces a pregnancy. Sexual intimacy can morph from an expression of closeness to a demand for conception. Each failed cycle is a multifaceted burden. In vitro fertilization (IVF) is rarely covered by insurance. Some individuals may even become suicidal with recurrent loss of pregnancy.

While we acknowledge that infertility and its treatment are physically and psychologically challenging, there is a paucity of research into the association between psychiatric illness and infertility (Table 1). Additionally, we know little about the psychological impact of infertility and prolonged exposure to infertility treatment on mood and well-being. As the current research stands, it is unclear how mood and anxiety disorders impact fertility and if infertility and its treatment may lead to mood and anxiety disorders.

Impact of affective disorders on fertility and its treatment

There are conflicting data regarding the impact of depression and anxiety on the reproductive cycle. In one study, it was observed that depressive symptoms were not associated with changes in reproductive hormone levels,2 but other studies have found that self-reported levels of stress do impact hormone levels.3 In a group of young women aged 17 to 20 years,higher ratings of stress were associated with lower estradiol (but not testosterone or progesterone) concentrations. This finding is consistent with previous studies suggesting that prolonged perceived stress may lower overall estradiol production, thus inhibiting ovulation and suppressing reproduction.

Inflammation may also play an important role in infertility, and current research suggests that chronic inflammation may affect fertility and pregnancy outcomes. Chronic stress, depression, and anxiety have all been associated with inflammation and, therefore, may interfere with attempts to conceive. In a study of women and men undergoing infertility treatment, higher stress levels were associated with various markers of inflammation, including higher cervicovaginal inflammatory cytokines. These inflammatory markers were, in turn, associated with a decreased likelihood of achieving pregnancy through IVF.4

It is likely that high levels of cumulative stress associated with recurrent depression and/or anxiety may affect multiple stages of fertilization. That said, normal levels of stress related to infertility treatment probably have minimal effects. A prospective study from Donarelli and colleagues5 examined anxiety and stress levels in women and men pursuing infertility treatment before undergoing ovarian stimulation. The researchers found that neither partners level of treatment-related stress had an impact on the number of ovarian follicles greater than 16 mm, with ovarian follicle size being a predictor of IVF success.

Health care providers can reassure patients that neither partners situational stress will impact follicle stimulation. Additionally, it has been speculated that chronic stress impedes successful implantation, but difficulty with implantation can be overcome using IVF. Although more research is needed, IVF may be a reasonable recommendation for women with mood disorders who are experiencing infertility.6

Although it is unclear whether depression affects fertility, it may have an impact on treatment with assisted reproductive technology (ART). Health care providers should be aware that women with depression are less likely to pursue infertility treatment. A recent prospective study of patients attending a fertility clinic found that women who screened positive for depression were about half as likely to initiate treatment for infertility compared with their nondepressed counterparts.7 Additionally, depression in women has been associated with higher ART dropout rates. One study found that couples with a clinically depressed female partner were 5 times more likely to discontinue treatment than couples with a nondepressed partner.8 Screening for depression is therefore important in couples pursuing infertility treatment, and extra care should be taken to provide appropriate support to patients seeking infertility treatment who screen positive for an affective disorder.

Eating disorders and infertility treatment

Infertility and subfertility may occur in women with anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). In women with active illness, amenorrhea and oligomenorrhea can compromise the likelihood of conception (Table 2). Menstrual irregularities occur most commonly in women with AN, with 39% to 42% experiencing amenorrhea (an absence of menstruation) and an additional 6% to 11% reporting oligomenorrhea (infrequent menstruation); however, 7% to 40% of women with BN report amenorrhea and 36% to 64% experience oligomenorrhea.9

The strongest predictors of amenorrhea in women with eating disorders are low body mass index (BMI), low caloric intake, and higher levels of exercise. Weight restoration is the primary intervention for amenorrhea in women with eating disorders, although amenorrhea may persist even after normal weight has been restored.In addition, polycystic ovarian syndrome (PCOS) may be another factor contributing to menstrual irregularity in this population, as PCOS is common among women with BN and BED. In fact, one study reported polycystic ovaries in 75% of women with BN.9

Women with a current eating disorder may experience fertility problems, especially if they have a low BMI and experience menstrual irregularity. However, data regarding the fertility of women with a history of an eating disorder have yielded mixed results.Many studies, including 2 large, population-based cohort studies, have demonstrated similar rates of successful pregnancy in women with a history of an eating disorder compared with women in the general population.10 At the same time, prospective data from the Avon Longitudinal Study of Parents and Children (ALSPAC) indicate that women with a history of AN or BN were more likely to take longer than 6 months to conceive and were more likely to have conceived with the aid of fertility treatment.11

While we do not have detailed information on the impact of other psychiatric disorders (such as bipolar disorder and schizophrenia) on fertility, it should be noted that certain medications used to treat these disorders may cause menstrual irregularities, including amenorrhea, and may thus negatively affect fertility. For example, antipsychotic agents with strong antagonism of the dopamine D2 receptor, such as risperidone and older antipsychotics, increase levels of prolactin, causing hypogonadotropic hypogonadism and subsequent menstrual dysfunction.12

Finally, drug and alcohol use disorders have well-documented effects on the fetus, but the effects on conception and implantation of an embryo are unclear. Studies have suggested that substance use disorder has a negative impact on female and male fertility, but more research is needed in this area.13 The majority of data have come from animal models. Studies in humans have been observational and are complicated by participants who use multiple substances and different routes of administration. Explicit associations between substance use and fertility is further confounded by lifestyle factors that often accompany substance use, such as overall unhealthy lifestyle, poor decision-making, and comorbid physical and mental health disorders.14

Psychological impact of fertility treatment

The decision to begin ART can be very stressful for couples, and research has shown that stress may increase with each subsequent fertility treatment.15 However, distress can manifest at any point during ART. In a large Dutch study following couples experiencing infertility (who reported undergoing an average of 4.3 fertility treatments over 5 years), a passive-avoidant method of coping (eg, hoping for a miracle) was linked with psychological distress in women, and this effect increased over time. For men, this coping style led to increased marital distress.16 Women who perceived infertility as central to their identity, and who were resistant to realigning their goals, reported greater distress during fertility treatment.17 On the other hand, meaning-based coping strategies, learning to grow from a negative experience, and/or finding other goals in life were associated with decreased distress in women, but not in men. A womans use of meaning-based coping strategies also decreased marital stress for both partners.16 It is important to note that these studies are based in countries where fertility treatment is covered by insurance, which is rare in the United States. American couples undergoing ART have additional stressors, although they would also likely benefit from these coping strategies.

Protective factors have also been identified. For a woman, having a higher level of education and adequate social supports decreases distress during ART. For men, a problem-solving coping strategy was linked to a higher self-reported quality of life (QOL).15 In a study from Israel, where there is a social emphasis on having children, researchers observed that maintaining daily routines and making efforts to feel normal led to a higher QOL and better adjustment to fertility treatment.18 In another study, the Dyadic Adjustment Scale (DAS), a tool that measures relationship distress, was administered to couples currently undergoing fertility treatment. Higher dyadic adjustment was associated with better QOL and less psychological distress in both men and women undergoing ART. However, this protective effect was diminished when infertility persisted for longer than 3 years.15

Although multiple studies have assessed psychological distress in couples undergoing treatment for infertility, far fewer have assessed the prevalence of clinically significant anxiety and depressive symptoms in this population. A large Danish study of couples undergoing ART found severe depressive symptoms in 11.6% of women and 4.3% of men.19 These symptoms correlated to an increase in infertility-related distress. However, there is considerable variation among studies with regard to rates of depression and anxiety in couples pursuing infertility treatment, which may reflect differences in type of ART, duration of infertility, number of failed cycles, cultural considerations, and methods used to assess symptoms.

According to another study, women who conceived through ART showed no difference in anxiety and depressive symptoms compared with pregnant women who conceived naturally. However, rates of depression and anxiety were higher in subfertile, nonpregnant women (57.6% and 15.7%, respectively).20 Comparisons between women undergoing repeated IVF cycles and first-time participants have suggested that ongoing treatment may lead to an increase in depressive symptoms, which may persist for 6 months after a failed ART trial.21

Recent research also suggests that both women and men with a history of major depressive disorder (MDD) are more likely to experience depressive symptoms during ART.22 In a prospective observational study of 25 women with a history of MDD undergoing ART, 44% of the women experienced a depressive relapse; rates of relapse were similar among women who maintained antidepressant use compared with those who discontinued treatment.23

In another study, researchers observed that among 108 women undergoing IVF for the first time, those with a history of unipolar depression or anxiety disorder reported more depressive symptoms than controls without these disorders. The group without psychiatric illness responded to fertility treatment with elevated cortisol levels (compared to baseline), whereas women with a history of mood or anxiety disorder had a blunted cortisol response. These results may indicate that infertile women with Axis I disorders may have chronically elevated levels of cortisol, even before entering into infertility treatment.24

Clinical recommendations

Steps should be taken to screen couples, not just women, for psychiatric disorders and chronic stress prior to beginning infertility treatment, as well as throughout treatment. Although depressive symptoms and anxiety occur frequently in women experiencing infertility, many women do not seek treatment. In fact, many women resist disclosing their mental health status to their reproductive endocrinologist for fear that they would be deemed bad candidates for infertility treatment. Effectively treating eating disorders, substance use disorders (including alcohol and tobacco use), and bipolar disorder from the initiation of infertility treatment will aid in a healthy pregnancy, if conception is successful.

Although there is no evidence to suggest that antidepressants or anxiolytic medications negatively affect fertility or infertility treatment, many women are reluctant to use medication in this setting. Women undergoing infertility treatment may not engage in treatment of anxiety and depression because they already feel overburdened by the demands of infertility treatment on their time and financial resources. In addition, having to pursue psychiatric treatment in this setting may accentuate the shame and stigma many women with infertility often feel.

Providing couples with information normalizes the psychological effects of infertility and its treatment may help patients adjust to and tolerate the process. Clinicians should give guidance when psychological symptoms are more than a normal reaction to a common reaction to failed ART. Counseling patients on the importance of self-care, healthy coping strategies, and improving communication may have a positive impact on both the individual and couple. Patient support can include connecting them with community support resources, such as RESOLVE (a network of groups affiliated with the National Infertility Association), and recommending a consultation with a sex therapist to help the couple maintain a positive connection with each other.

Additionally, targeted psychological interventions may help alleviate the adverse psychological outcomes associated with infertility and its treatment, including anxiety, depressive symptoms, and marital stress (Table 3). According to a recent meta-analysis25 that included 39 studies and a total of 3064 women and 347 men, psychological interventions, most commonly cognitive behavioral therapy (CBT) or mind-body interventions (MBI), may be effective for reducing anxiety (25 studies), as well as depressive symptoms (21 studies). These interventions also appeared to improve rates of pregnancy; in this meta-analysis, women treated with CBT or MBI were about twice as likely to achieve pregnancy compared with women receiving usual care. Of note, larger reductions in anxiety were associated with greater improvements in pregnancy rates.

To date, there is no research that specifically looked at the pharmacologic treatment of depression or anxiety in women with infertility. Thus, the same principles that guide the treatment of women during pregnancy should inform the treatment of women undergoing infertility treatment. There are sufficient data to support the use of selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRIs and SNRIs), bupropion, and tricyclic antidepressants. Other factors that may influence the selection of an antidepressant include prior response to a particular antidepressant, comorbidity of anxiety symptoms, and adverse effect profile.

Benzodiazepines, including lorazepam and clonazepam, may be helpful for the management of anxiety disorders, treatment-emergent anxiety, and sleep disturbance. Althoughearlier reports suggested an increased risk of cleft lip and palate associated with prenatal benzodiazepine exposure, more recent reports have shown no increase in the overall risk of malformations in children exposed to benzodiazepines during pregnancy.26

Many women question whether the use of these medications may affect fertility or the success of infertility treatment. Although there is no evidence to indicate that antidepressants or benzodiazepines have deleterious effects on fertility, this has not been studied systematically. There have been reports suggesting a small but statistically significant increase in risk of miscarriage in women treated with SSRIs, although this is not a universal finding.27 It is also important to note that women who suffer from mood and anxiety disorders probably carry a slightly higher risk of miscarriage. In fact, women with a history of depression who stop treatment with an antidepressant 3 to 12 months prior to conception have the same risk of miscarriage as women who continue treatment with an antidepressant.28

Although avoiding treatment with a medication may seem like the safest option, untreated anxiety and/or depression in the mother has been associated with negative pregnancy outcomes, including increased risk of preterm birth, low birth weight, and other complications.29 In addition, depression during pregnancy is a robust predictor of postpartum depression. Numerous somatic complaints are treated with medication during pregnancy; psychological complaints can be just as detrimental and should be treated, as well.

Concluding thoughts

Infertility is a common and psychologically distressing experience, both for the individual and the couple. Although there is a dearth of research examining the association between infertility and psychiatric illness, preliminary research indicates that depression, anxiety, and chronic stress may contribute to inflammation and alterations in hormone levels, factors which may affect the likelihood of successful pregnancy outcomes. Additionally, ongoing infertility treatment has been linked to increased depressive symptoms and anxiety and may hinder couples ability to pursue and continue with infertility treatment.As noted, eating disorders can also affect fertility.

Increased psychological support during infertility treatment would be beneficial for this population and may improve the chances of a successful pregnancy. The patient undergoing infertility treatment should be given the same plan of care as any patient with anxiety or depression. Support should include expectation management around the psychological effects of infertility treatment, as well as promotion of healthy coping strategies, such as taking time for self-care. If needed, pharmacotherapy with SSRIs or benzodiazepines is unlikely to have an adverse effect on conception and may decrease ART dropout. However, more research is needed to establish the connection between psychological illness and depression in order to create effective targeted therapies.

CME POST-TEST

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References

1. Reproductive Health: Infertility FAQs. Centers for Disease Control and Prevention. Updated January 16, 2019. Accessed November 7, 2019. https://www.cdc.gov/reproductivehealth/infertility/index.htm

2. Prasad A, Schisterman EF, Schliep KC, et al. Depressive symptoms and their relationship with endogenous reproductive hormones and sporadic anovulation in premenopausal women. Ann Epidemiol. 2014;24(12):920-924.

3. Roney JR, Simmons ZL. Elevated psychological stress predicts reduced estradiol concentrations in young women. Adapt Human Behav Physiol. 2015;1(1):30-40.

4. Haimovici F, Anderson JL, Bates GW, et al. Stress, anxiety, and depression of both partners in infertile couples are associated with cytokine levels and adverse IVF outcome. Am J Reprod Immunol. 2018;79(4).

5. Donarelli Z, Lo Coco G, Gullo S, et al. Infertility-related stress, anxiety and ovarian stimulation: can couples be reassured about the effects of psychological factors on biological responses to assisted reproductive technology? Reprod Biomed Soc Online. 2016;(3):16-23.

6. Zaig I, Azem F, Schreiber S, et al. Womens psychological profile and psychiatric diagnoses and the outcome of in vitro fertilization: is there an association? Arch Womens Ment Health. 2012;15(5):353-359.

7. Crawford NM, Hoff HS, Mersereau JE. Infertile women who screen positive for depression are less likely to initiate fertility treatments. Hum Reprod. 2017;32(3):582587.

8. Pedro J, Sobral MP, Mesquita-Guimares J, . Couples discontinuation of fertility treatments: a longitudinal study on demographic, biomedical, and psychosocial risk factors. J Assist Reprod Genet. 2017;34(2):217-224.

9. Kimmel MC, Ferguson EH, Zerwas S, Bulik CM, Meltzer-Brody S. Obstetric and gynecologic problems associated with eating disorders.Int J Eat Disord. 2016;49(3):260-275.

10. Tabler J, Utz RL, Smith KR, Hanson HA, Geist C. Variation in reproductive outcomes of women with histories of bulimia nervosa, anorexia nervosa, or eating disorder not otherwise specified relative to the general population and closest-aged sisters.Int J Eat Disord. 2018;51(2):102111.

11. Schmidt U, Sharpe H, Bartholdy S, et al. Treatment of anorexia nervosa: a multimethod investigation translating experimental neuroscience into clinical practice. Programme Grants Appl Res. 2017;5(16):95-107.

12. Lania A, Gianotti L, Gagliardi I, Bondanelli M, Vena W, Ambrosio MR. Functional hypothalamic and drug-induced amenorrhea: an overview. J Endocrinol Invest. 2019;42(9):1001-1010.

13. Sansone A, Di Dato C, de Angelis C, et al. Smoke, alcohol and drug addiction and male fertility.Reprod Biol Endocrinol. 2018;16(1):3.

14. de Angelis C, Nardone A, Garifalos F, et al. Smoke, alcohol and drug addiction and female fertility.Reprod Biol Endocrinol. 2020;18(1):21.

15. Zurlo MC, Cattaneo Della Volta MF, Vallone F. Predictors of quality of life and psychological health in infertile couples: the moderating role of duration of infertility. Qual Life Res. 2018;27(4):945-954.

16. Peterson BD, Pirritano M, Christensen U, et al. The longitudinal impact of partner coping in couples following 5 years of unsuccessful fertility treatments. Hum Reprod. 2009;24(7):1656-1664.

17. Neter E, Goren S. Infertility centrality in the womans identity and goal adjustment predict psychological adjustment among women in ongoing fertility treatments. Int J Behav Med. 2017;24(6):880-892.

18. Benyamini Y, Gozlan M, Weissman A. Normalization as a strategy for maintaining quality of life while coping with infertility in a pronatalist culture. Int J Behav Med. 2017;24(6):871-879.

19. Peterson BD, Sejbaek CS, Pirritano M, Schmidt L. Are severe depressive symptoms associated with infertility-related distress in individuals and their partners? Hum Reprod. 2013;29(1):76-82.

20. Joelsson LS, Tydn T, Wanggren K, et al. Anxiety and depression symptoms among sub-fertile women, women pregnant after infertility treatment, and naturally pregnant women. Eur Psychiatry. 2017;45:212-219.

21. Milazzo A, Mnatzaganian G, Elshaug AG, et al. Depression and anxiety outcomes associated with failed assisted reproductive technologies: a systematic review and meta-analysis. PLoS ONE. 2016;11(11): e0165805.

22. Holley SR, Pasch LA, Bleil ME, et al. Prevalence and predictors of major depressive disorder for fertility treatment patients and their partners. Fertil Steril. 2015;103(5):1332-1339.

23. Freeman MP, Lee H, Savella GM, et al. Predictors of depressive relapse in women undergoing infertility treatment. J Womens Health. 2018;27(11):1408-1414.

24. Zaig I, Azem F, Schreiber S, et al. Psychological response to cortisol reactivity to in vitro fertilization treatment in women with a lifetime anxiety or unipolar mood disorder diagnosis. J Clin Psychiatry. 2013;74(4):386-92.

25. Frederiksen Y, Farver-Vestergaard I, Skovgrd NG, et al. Efficacy of psychosocial interventions for psychological and pregnancy outcomes in infertile women and men: a BMJ Open. 2015;5(1):e006592.

26. Andersen JT, Andersen NL, Horwitz H, et al. Exposure to selective serotonin reuptake inhibitors in early pregnancy and the risk of miscarriage. Obstet Gynecol. 2014;124(4):665-61.

27. Grigoriadis S, Graves L, Peer M, et al. Benzodiazepine use during pregnancy alone or in combination with an antidepressant and congenital malformations: systematic review and meta-analysis. J Clin Psychiatry. 2019;80(4).

28. Jarde A, Morais M, Kingston D, et al. Neonatal outcomes in women with untreated antenatal depression compared with women without depression: a systematic review and meta-analysis. JAMA Psychiatry. 2016;73(8):826-837.

29. Wu P, Velez Edwards DR, Gorrindo P, et al. Association between first trimester antidepressant use and risk of spontaneous abortion. Pharmacotherapy. 2019;39(9):889-898.

Read the original here:
The Intertwining Effect of Mood Disorders and Infertility - Psychiatric Times

Recommendation and review posted by Bethany Smith

Hundreds of physicians and other medical professionals in the Abortion Pill Rescue Network aid women who experience regret after starting the chemical abortion process. And each provider has their own story for how they came to help women in this critical situation have a second chance at life for their child.

According to a recent report from the Charlotte Lozier Institute (CLI), a "surge" in chemical abortions is contributing to a rise in abortion rates.

Chemical abortion is a two-pill process. The first chemical, mifepristone (or RU-486) is the first pill used in a chemical abortion and blocks the effects of progesterone, a hormone necessary for a pregnancy to thrive. The second part, misoprostol, expels the baby.

However, some moms take that first chemical abortion pill and then regret doing itwhich is why the Abortion Pill Rescue Network (APRN), managed by Heartbeat International, plays such a critical role.

Available 24/7 through the network for moms who experience such regret, the abortion pill reversal (apr) protocol offers hope that the chemical abortion process may be reversed if initiated within a specific timeframe.

When one of these women connects with Heartbeats Option Line, consultants assist women with immediate needs before referring them to the nearest one of more than 700 Abortion Pill Rescue (APR) providers worldwide in the APRN.

[Click here to subscribe to Pregnancy Help News!]

One of those providers is Karen D. Poehailos, MD, who has been working with the APRN since 2015. She has successfully helped a number of moms and their babiesincluding her very first reversal baby, who recently turned five years old.

In celebration of this milestone, I spoke with Poehailos to learn more about her background, her journey to the pregnancy help community, her experiences as an APRN provider, and the impact this has had upon her life.

Poehailos is a board-certified family physician and the Regional Medical Director for ThriVe Central VA Women's HealthCare, a group of four womens health care centers with locations in Charlottesville, Albemarle, Culpeper and Orange, Virginia. She is also a family physician part-time at WellFamily Medicine in Charlottesville.

Her responsibilities with ThriVe Central Virginia include oversight of the paid and volunteer medical personnelas well as providing and coordinating limited obstetrical ultrasound, medical visits, and testing and treatment for sexually transmitted infections (STIs) and sexually transmitted diseases (STDs).

Poehailos is a graduate of the University of Virginia School of Medicine and its Family Medicine Residency. She has worked in primary care and urgent care settings, and has taken additional training in Natural Family Planning and is a Certified FertilityCare Medical Consultant, working with women on issues like recurrent miscarriage, infertility and irregular cycles without use of IVF or hormonal contraception.

Shes been a practitioner for the APRN since 2015 and a member of the Heartbeat International Medical Advisory Council and the Heartbeat International Abortion Pill Reversal (APR) Advisory Team since 2019.

A native of Baltimore, Poehailos now makes her home in Charlottesville, Virginiawhere she embraced the challenge of raising four sons through Scouts, sports and band carpools while still maintaining a medical practice and volunteer life at her church.

For many years, Poehailos worked off and on as a volunteer for ThriVe Central Virginia. However, in early 2018 she moved into part-time employment, then became a full-time physician there in June of 2018which she says is an unusual arrangement for pregnancy resource centers, since medical directors are usually volunteers or part-time employees.

Acknowledging the significant step forward in faith it took for the centers to commit to offering her a full-time role, she says that although she was excited, she was also nervous about leaving the employer shed been with for 20 years.

I felt like I was leaving my security blanket, she said. It was a step of faith to leave that job, because I love family medicine and I love doing urgent care, but I just kind of felt the nudge from God.

However, in the midst of the transition, she learned that her former employer had decided to close his doorswhich meant she wouldve suddenly been out of a job if shed stayed.

So, God definitely took care of me, she said.

In this context, Poehailos says she can clearly see how God has used a variety of seemingly disparate skills and circumstances to guide her to her current role.

Noting that the four centers now offer STI testing and treatment, she said, Before I went to medical school, I was a medical technologist and did hospital lab work. The fact that I already had a good lab background helped us get that off the ground. And Im actually comfortable drawing blood because I worked in a blood bank for a while.

She says another much-needed skill shes developed in recent years is the ability to perform her own ultrasounds.

I did training in limited OB ultrasounds so I can conduct the scans myself, in addition to reading them, Poehailos said.

Citing Esther 4:14 as one of her favorite verses, she said, You know, this is the moment for which you've been created. I mean, why was I a med tech before I decided to go to medical school? Well, it finally became clear much later.

Poehailos says her journey to becoming an APRN provider started with a natural family planning meeting in Milwaukee in 2010. It was during lunch with two other physicians that she first heard about the use of progesterone after a woman took the first dose of the abortion pill to try to reverse the abortion.

I thought, Wow, that sounds really interesting, she said. But I didn't have that much familiarity with working with progesterone and I kind of filed the information away in my head.

It was a year or so later, Poehailos said, when she took the FertilityCare medical consultant course at the Saint Paul VI Institute in Omaha, and, one of the primary tools in our toolbox was to use progesterone for women with threatened miscarriage and women with certain cycle irregularities. Once I took that course and got comfortable with progesterone, I knew I was ready to join the APRN hotline as a provider.

When she first got involved, the APRN was operated by Dr. George Delgado through Culture of Life Family Services in San Diego. The APRNs operations transitioned to Heartbeat International in 2018.

Poehailos vividly remembers the first call she received in February of 2015. She was with one of her sons, visiting a university campus and walkway over Interstate 81 on a pedestrian bridge.

My phone vibrates in my pocket and I pull it out and theres a text that says, Hi, this is the hotline. We might have a patient for you, she recalled.

After telling her son to go to the next lecture without her, she found a spot in the lobby of a building and talked to the hotline nurse, then called the patient. When they returned to Charlottesville later that afternoon, Poehailos said, I met her at the office, and we started the protocol.

That first patient was also her first successful reversal; the healthy little girl who recently turned five.

Over time, her experiences have taught her how to prepare women regarding what to expect once the reversal process has startedwhich is an important part of helping them cope with everything thats going on in their lives.

We have to remember that whatever circumstances led the woman to start the medical abortionher social situation or whatever was an influencing factor in her decisiondoesn't magically go away when she attempts to rescue that abortion attempt, said Poehailos. So whatever else was stressing her with her family or her boyfriend or whatever is going on, we have to always remember when we're in contact with these women afterwards, that those things didn't magically disappear.

They are going to need more support than the average woman who may be threatening a miscarriage for another reason, she added.

As far as follow-up, she says she tries to stay in contact with women until they can receive care from a local obstetrician.

Our mission is to get them turned over to local OB care, Poehailos explained. I always tell them when I'm seeing them for the ultrasound that they need to get established with an OB physician and Ill be happy to share any needed information.

Poehailos says being an APRN provider has had a big impact on herespecially when she gets good news about how the moms and children have been thriving since her first contact with them.

One reached out to text me a couple of years ago on Mother's Day and said, Happy Mother's Day to you. And thank you. Here's a picture of my baby, said Poehailos. It just makes you want to cry.

She also recalled how five years ago when the first baby she helped was about to enter the world, the mom asked her to come to the hospital to meet the baby after she was born.

She wasnt that far from away from us, Poehailos said, so I was able to go to the hospital at her request, the day of the delivery to see the baby. The mom took a picture of me holding the baby the day she was born. That's a picture for forever.

Poehailos says one of the challenges with APR is the critical timing thats requiredsince the woman needs to be seen right away to start the protocol. Fortunately, the APRN providers help each other out, she said, providing creative support to meet patient needs.

There's nice collaboration between the providers on the network, Poehailos said. One way or another, weve always managed to get it done.

Referring to the APRN as the emergency room for pregnancy resource clinics, Poehailos said, Were like the code team in a hospital. You have to get there now.

Other times, when women come in and they're still considering all their options, it's not as urgent, she said. But with APR theres much more urgency since the process has already been started and we have to stop it. Somebody needs to be there pretty fast to get the ball rolling. We all pitch in to make sure that happens.

Tweet This: With Abortion Pill Rescue theres urgency as the process has been started & we have to stop it. We all pitch in to make sure that happens.

In terms of ongoing needs, Poehailos says she wants to spread the word about the APRNespecially to other providers who may want to become part of something that makes such a difference.

Theres a great need for more local providers, she says, so women who are already in crisis wont be required to travel long distances to access the urgent care thats required.

We have a lot of providers in the network, but were not evenly distributed geographically, Poehailos said.

And even if theres an APRN provider already in a specific area, Poehailos said it would be a big help to have more than one, so they could back each other up to meet local needs.

If one provider isnt available when a woman needs their services, it would be awesome to have another provider in that same city, said Poehailos, instead of making the woman drive several hours to receive care.

Poehailos says shes been grateful for the increased resources that became available when the Heartbeat International assumed oversight of the APRN.

The people who started APR did an amazing job to get the ball rolling, said Poehailos. Im grateful Heartbeat International was able to step in and put the strength of their network and Option Line behind the network, because we really needed that to have the increased reach.

If you are a woman in need of Abortion Pill Rescue care, representatives are available 24/7 through Option Line to speak with you. Click HERE, call 1-800-712-4357 or text HELPLINE to 313131.

If you are a healthcare provider interested in becoming part of the APRN, you can learn more by visiting the Abortion Pill Rescue Network page.

Editor's note: Heartbeat International manages the Abortion Pill Rescue Network, Option Line and pregnancy Help News.

Go here to see the original:
A nudge from God one doctor's journey to serving other women through Abortion Pill Rescue - Pregnancy Help News

Recommendation and review posted by Bethany Smith

For patients with hormone receptor (HR)positive, HER2-negative breast cancer, research reported that adding ribociclib (Kisqali) to endocrine therapy significantly improved overall survival (OS) while delaying subsequent chemotherapy when compared with placebo, regardless of endocrine partner, according to results presented during the 2020 San Antonio Breast Cancer Symposium.1

An updated analysis of the phase 3 MONALEESA-7 trial (NCT02278120) reported a median follow-up of 53.5 months (range, 46.9-66.4), and the median OS with ribociclib plus endocrine treatment was 58.7 months vs 48.0 months with placebo/endocrine therapy (HR, 0.763; 95% CI, 0.608-0.956), translating to a 24% relative reduction in the risk of death with the CDK4/6 inhibitor.

Moreover, data from a subgroup analysis examining survival in relation to endocrine partner, results showed that patients who received a nonsteroidal aromatase inhibitor (NSAI) experienced a median OS of 58.7 months with ribociclib/endocrine therapy vs 47.7 months with placebo/endocrine therapy (HR, 0.798; 95% CI, 0.615-1.04). In those who received tamoxifen, the median OS had not yet been reached with ribociclib vs 49.3 months with placebo (HR, 0.705; 95% CI, 0.453-1.097).

A consistent significant OS benefit with ribociclib plus endocrine therapy was demonstrated after a longer median follow-up of 53.5 months. With a median OS of 58.7 months in the ribociclib arm, this is the longest median OS [that we have seen] among the phase 3 trials for HR-positive, HER2-negative advanced breast cancer, Debu Tripathy, MD, professor and chairman of the Department of Breast Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, said in a poster presentation during the meeting. Therefore, this exploratory analysis confirms the benefit and continued use of ribociclib in the first-line setting for pre- or perimenopausal patients with HR-positive, HER2-negative advanced disease.

In the multicenter, double-blinded, placebo-controlled phase 3 MONALEESA-7 trial, investigators set out to evaluate the efficacy of ribociclib in pre- and perimenopausal patients with HR-positive, HER2-negative advanced breast cancer. To be eligible to participate, patients needed to have received at least 1 previous line of chemotherapy for advanced disease and they could not have been administered prior endocrine treatment.

A total of 672 patients were randomized 1:1 to receive either ribociclib at a daily dose of 600 mg 3-weeks-on/1-week-off (n = 335) or placebo (n = 337) in combination with goserelin plus either a NSAI or tamoxifen. The primary end point of the trial was progression-free survival (PFS), and key secondary end points comprised OS, health-related quality of life, overall response rate (ORR), time to definitive deterioration of the ECOG performance status, PFS2, and safety, among others.

Patient characteristics were found to be well balanced between the 2 treatment arms. The median age of participants in the investigational arm was 43 years.2 Moreover, 55.8% were white, 29.6% were Asian, and 8.7% were black, Native American, or other. The race of 6.0% of patients was unknown. The ECOG performance status of 73.1% of patients was 0; it was 1 in 26.0%, and unknown for the remaining 0.9%. More than half, or 57.6%, of patients had visceral metastases, with 24.2% of them having bone-only metastases.

Earlier data showed that ribociclib plus endocrine therapy was found to significantly improve PFS and OS compared with placebo/endocrine therapy in this patient population. Specifically, the median PFS was 23.8 months in the investigational arm vs 13.0 months in the control arm (HR, 0.55; 95% CI, 0.44-0.69; P < .0001).3,4 At a median follow-up of 34.6 months, the median OS reported in the final protocol-specified OS analysis had not yet been reached in the ribociclib arm vs 40.9 months in the placebo arm (HR, 0.71; 95% CI, 0.54-0.95; P = .00973).

After the prior analysis, patients were unblinded and 15 patients in the placebo arm crossed over to receive ribociclib, Amy S. Clark, MD, MSCE, assistant professor of medicine at the Hospital of the University of Pennsylvania, commented in a poster spotlight session during the meeting. The median OS had not been reached in the ribociclib group in that initial OS analysis, so I do think it was important to continue to follow these results.

Results from an exploratory subgroup analysis presented at the meeting proved to be consistent with the OS data reported for the overall patient population. However, investigators noted that this should be interpreted with caution because of the small numbers of patients, relatively wide confidence intervals, and a lack of statistical power, said Tripathy.

As of the June 29, 2020 data cutoff, 21.2% of patients on the ribociclib/endocrine therapy arm and 9.2% of those on the placebo arm were still receiving treatment. Almost 80% (78.8%) of patients on the investigative arm had ended treatment vs 90.8% of those on the control arm.

On the ribociclib arm, the majority of patients, or 62.7%, discontinued due to disease progression, noted Tripathy. Additionally, 6.3% of these patients discontinued due patient/guardian decision, 3.6% due to physician decision, 4.8% due to an adverse effect (AE), 0.9% due to death, and 0.6% were lost to follow-up.

Moreover, 77.3% of those on the ribociclib/endocrine therapy arm vs 78.1% of those on the placebo/endocrine therapy arm went on to receive subsequent therapy. The most common first subsequent therapies were chemotherapy alone and hormone therapy alone.

Subsequent treatments received in the investigative and control arms included chemotherapy (22.3% vs 28.4%, respectively), chemotherapy plus hormone therapy or other therapy (10.2% vs 10.1%), hormone therapy alone (27.7% vs 18.3%), hormone therapy plus other therapy (15.2% vs 18.0%), or other treatment (1.9% vs 3.3%).

Moreover, more patients on the placebo arm went on to receive a CDK4/6 inhibitor following treatment discontinuation. Almost 13% of patients on the investigative arm went on to receive another CDK4/6 inhibitor vs 26.1% of those on the control arm. Among the patients on the investigative arm, 9.5% received palbociclib (Ibrance), 2.3% received ribociclib, and 1.5% received abemaciclib (Verzenio). In the control arm, 21.9%, 3.9%, and 0.7% of patients received palbociclib, ribociclib, or abemaciclib, respectively.

The median time to chemotherapy was 50.9 months with ribociclib plus endocrine therapy vs 36.8 months with placebo plus endocrine therapy (HR, 0.694; 95% CI, 0.556-0.867). Moreover, the median chemotherapy-free survival in the investigative and control arms was 42.4 months vs 26.4 months, respectively (HR, 0.666; 95% CI, 0.550-0.808). Lastly, the median PFS2 with ribociclib was 44.2 months vs 31.0 months with placebo (HR, 0.683; 95% CI, 0.560-0.834).

The toxicities in the safety population proved to be consistent with those observed in the primary and final OS analyses, according to Tripathy. AEs of special interest in the ribociclib and placebo arms included all-grade neutropenia (77.9% vs 10.7%, respectively), leukopenia (35.5% vs 5.9%), anemia (22.7% vs 11.6%), hepatobiliary toxicity (29.3% vs 23.7%), QTc prolongation (12.8% vs 6.5%), and interstitial lung disease/pneumonitis (0.6% vs 0%, respectively).

The most commonly reported grade 3 or higher AE in the ribociclib arm was neutropenia (53.1%, grade 3; 11.6%, grade 4). In the control arm, hepatobiliary toxicity was the most frequently experienced grade 3 effect (6.8%), while neutropenia (0.9%) was the most common grade 4 toxicity.

The OS benefit of those receiving ribociclib and endocrine therapy, regardless of the endocrine therapy partner, was sustained in this longer-term follow-up, concluded Clark. The addition of ribociclib also lengthens time to chemotherapy and chemotherapy-free survival, which I think is an incredibly important outcome for these patients who live for many years and who would like to delay the time to chemotherapy for as long as possible. I believe that these data are continued evidence that ribociclib should be considered for use in pre- and perimenopausal women with newly diagnosed [estrogen receptor]positive metastatic breast cancer.

References:

1. Tripathy D, Im S-A, Colleoni M, et al. Updated overall survival (OS) results from the phase III MONALEESA-7 trial of pre- or perimenopausal patients with HR+/HER2- advanced breast cancer (ABC) treated with endocrine therapy (ET) +/- ribociclib. Presented at: 2020 San Antonio Breast Cancer Symposium; December 8-11, 2020; Virtual. Abstract PD2-04. https://bit.ly/33WH2ly.

2. Tripathy D, Im S-A, Colleoni M, et al. First-line ribociclib or placebo combined with goserelin and tamoxifen or a nonsteroidal aromatase inhibitor in premenopausal women with hormone receptorpositive, HER2-negative advanced breast cancer: results from the randomized phase 3 MONALEESA-7 trial. Presented at: 35th Annual Miami Breast Cancer Conference; March 8-11, 2018; Miami, FL. Abstract 626.

3. Tripathy D, Im S-A, Colleoni M, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018;19(7):904-915. doi:10.1016/S1470-2045(18)30292-4.

4. Im S-A, Lu Y-S, Bardia A, et al. Overall survival with ribociclib plus endocrine therapy in breast cancer. N Engl J Med. 2019;381(4):307-316. doi:10.1056/NEJMoa1903765.

Excerpt from:
Significant Survival Benefit Found with Ribociclib to Treat HR+/HER2- Breast Cancer - Cancer Network

Recommendation and review posted by Bethany Smith

Imagine being a doctor and having a precocious resident permanently by your side, giving you brilliant insight into disease and helping you to identify the best treatment path for your patients.

A team at Salesforce Research believes this scenario is closer to reality than you might think, as a result of a series of exciting developments in AI vision technology and machine learning.

Breast cancer affects more than two million women worldwide each year, with around one in eight women in the United States developing breast cancer over the course of their lifetime. There were also 2,550 new cases of breast cancer in men in the U.S. in 2018. Alarmingly, rates of breast cancer are increasing in nearly every region globally.

Salesforce Research collaborated with the Ellison Institute to develop ReceptorNet, a deep-learning algorithm that can determine hormone-receptor status - a crucial biomarker for clinicians when deciding on the appropriate treatment path for breast cancer patients - with excellent sensitivity and specificity numbers. This work has been published in the journal Nature Communications under the title 'Deep learning-enabled breast cancer hormonal receptor status determination from base-level H&E stains.'

While using AI to try to improve outcomes for breast cancer patients is not new, efforts up until now - such as Google's AI breast cancer screening tool - have largely focused on diagnosing cancer.

What makes ReceptorNet unique is that it focuses on improving the way treatment decisions are made for breast cancer patients. Specifically, ReceptorNet predicts hormone-receptor status from an inexpensive and ubiquitous tissue image. That's in contrast to the current standard of care, which requires both a more expensive, less widely available type of tissue image - and a trained pathologist to review those images.

Crucially, because it is a less expensive and quicker way of determining hormone-receptor status than the system used commonly today in countries like the U.S., it could potentially help make high-quality decision-making for breast cancer therapies more accessible - allowing patients globally to receive the best possible treatment path, regardless of the expertise available in their healthcare system.

The development of ReceptorNet originated in conversations between Salesforce researchers and Dr. David Agus, Founding Director and CEO of the Lawrence J. Ellison Institute for Transformative Medicine of USC.

Dr. David Agus, Founding Director & CEO, Lawrence J. Elison Institute for Transformative Medicine of USC

Dr. Agus is a renowned oncologist and a professor of medicine and engineering. He explains that there has long been a belief among cancer doctors that tumor cells contain crucial information about cancer that the human brain can't quite extract.

'The human brain is very good at determining whether or not there is cancer based on looking at patterns in cells,' says Dr. Agus, 'but it can't determine the subtle differences in these patterns that correlate with the outcome of the cancer. In other words, what the molecular on/off switch is.'

This means that a patient might be diagnosed with cancer but then have to wait weeks for the results of molecular studies to determine what treatment they should receive.

'Our team has been working on using AI to understand patterns of cells and help make treatment decisions for several years. We had this notion that maybe we could find the answer to those molecular questions instantaneously with AI and machine learning,' Dr. Agus says.

That's where the Salesforce Research team came in. 'We have a world-class AI research team,' says Nikhil Naik, Lead Research Scientist at Salesforce Research and the first author on this study, adding that, 'the collaboration also matched our philosophy of developing technology that doesn't just serve the purpose of the company, but also has a positive impact on people and on the world.'

With a PhD in computer vision from MIT, Naik says he realized early on that Salesforce would be in an ideal position to help.

The algorithm is able to determine subtle patterns the human eye can't possibly perceive.

The team developed an AI solution that is able to extract vital clues about breast cancer by learning to spot patterns in images of tumors, using a cheap and widely available imaging process. Naik gives a simple analogy.

Say you have an accident and you think you may have broken your arm. What if, instead of having to go to the hospital for an X-ray, you could just take a photo of your arm on your cell phone and an AI algorithm could determine whether or not you had a fracture?

'That is very similar to what we are doing. We are replacing an expensive, time-consuming process that requires specialized technology with a simpler, more widely available technology for imaging, using artificial intelligence.'[MC(2]

So how does this work in practice? Typically, when a patient is diagnosed with breast cancer, a pathologist will analyze their tumor tissue under a microscope using a process called immunohistochemistry (IHC) staining, to look for the presence of hormone receptors that allow the cancer to grow. This helps them to decide on the best course of treatment, such as hormone therapy or chemotherapy.

The problem with IHC staining is that it is expensive, time-consuming, and not readily available in many parts of the world, particularly in developing countries.

ReceptorNet has learned to determine hormone receptor status by using a much less expensive and simpler imaging process - hematoxylin and eosin (H&E) staining - that analyzes the shape, size, and structure of cells.

ReceptorNet has been trained on several thousand H&E image slides, each containing billions of pixels, from cancer patients in dozens of hospitals across the world.

'The algorithm is able to look at individual pixels and determine subtle patterns that the human eye can't possibly perceive,' says Andre Esteva, Head of Medical AI, and co-author on the study, explaining that patterns can yield vital clues about how to treat the cancer.

An illustrative interpretation of how AI can spot what the human eye can't see

Since early 2019, Naik and Esteva have been leading a team at Salesforce that focuses on delivering AI applications for social good, primarily in the areas of medicine and science. Recently, the team created search engines for COVID-19 to help researchers and clinicians find information faster.

'There's a significant benefit to doing this kind of AI research in industry, as opposed to academia. AI teams tend to flourish when provided with industrial scale compute capabilities - and industrial scale budgets - because those elements make it much easier to rapidly experiment,' says Esteva.

'I think the most impactful applications of AI will be in healthcare,' adds Research Scientist Ali Madani, who assisted on the computer vision algorithm that powers ReceptorNet.

Madani talks passionately about the transformative impact AI could have on people's lives. 'There are direct applications that could improve society as a whole,' he says. 'That's the underlying motivation which has drawn me to AI and healthcare.'

An algorithm that's only 80% accurate is not good enough for a critical application, like determining which cancer therapy to give to a patient.

So, what could this mean for clinicians and patients? The ability to determine hormone-receptor status from H&E stains could make treatment less expensive and more readily available, particularly in developing countries.

It could also, says Dr. Agus, mean patients are spared an agonizing wait between diagnosis and the initiation of treatment.

Proposing a future use case of this new technology, Dr. Agus said to, 'Imagine when a woman comes in for her diagnosis and we can tell her right there on the spot what her treatment should be. Or in a third-world country (where molecule tests aren't available), imagine potentially being able to, just by scanning a slide, tell a woman that she can get a pill that could put her breast cancer under control. All of a sudden there's a transformation in medicine.'

In order for AI in medicine to deliver its full potential, clinicians must first have confidence in its accuracy.

'An algorithm that's only 80% accurate is not good enough for a critical application, like determining which cancer therapy to give to a patient,' acknowledges Naik.

In the test phase of the ReceptorNet project, when the algorithm was tested on images it had never seen before, it achieved 92% accuracy for hormone receptor determinations, which indicates its potential for future clinical deployment.

Numerous small, incremental changes were made to ensure the algorithm was able to deliver accurate predictions, regardless of differences in the preparation of the tissue samples it was analyzing. Crucially, the algorithm has also been able to deliver reliable performance across different demographic groups.

There have long been concerns that healthcare and evidence-based medicine can be biased against certain groups, because they are often underrepresented in the evidence base. However, during the development of ReceptorNet, researchers were able to achieve accurate results across a variety of different groups, which could be vital in order to build confidence in the performance of the AI among healthcare professionals.

Naik says, 'We analyzed this by splitting the data based on things like age, race, and location, and statistically there was no difference in the performance of the algorithm.'

Throughout the design process, the Salesforce team worked closely with Dr. Agus, Dr. Dan Ruderman, and Dr. Michael F. Press at The Ellison Institute, to ensure they were aware of any possible biases that could exist in the data that was fed into the model. This close collaboration also helped to ensure that the objectives of the team were closely aligned with the clinical workflows and questions that clinicians, doctors, and nurses would be interested in.

Despite this, the team was aware that not every medical professional would be easily convinced that AI could be relied upon.

Naik says that the pathologists they spoke to were initially skeptical, explaining that this kind of prediction based on an H&E slide is not something pathologists could do on their own.

'However, when they saw that the algorithm was working so well, they were really impressed that it was able to make these predictions just by learning from thousands of images - and also that it was able to confirm their suspicions about what kinds of patterns could be predictive. That was very impressive and exciting for them.'

Dr. Agus agrees. 'When we first started looking at how we could answer molecular questions instantaneously with AI and machine learning, we achieved some good results. But when we teamed up with Salesforce, those results went from good to great.'

But when we teamed up with Salesforce, those results went from good to great.

From a clinical perspective, this technology could eventually lead to a number of positive impacts. In a developed country such as the U.S., it could reduce the cost of care and the time it takes to initiate breast cancer treatment, because it uses much less expensive imaging technology and automated decision-making. It could also improve accuracy and deliver better outcomes for patients.

In developing countries where there is limited access to IHC staining, it could have a big impact in terms of broadening access to treatment.

The immediate effect of this work is to lay a foundation for future studies to compare the clinical workflow of a pathologist with and without this type of AI, in order to better understand its full potential.

Dr. Agus says that, 'This is just the tip of the iceberg with what we're going to be able to do with AI in cancer care. It's just a pilot project to show what's doable. Now, we can get deeper and deeper, and I can envisage a day not too far away, when just by looking at a slide, I can tell, with the help of AI, tell somebody 'you're going to get Drug X and not Drug Y because of how the cells are arranged'.'

For Esteva, one of the most exciting things about this project is that it has shown how AI can do more than just mimic the role of a doctor.

'What we're doing here is actually training AI to do something that the physician can't do, as an added capability to their repertoire. The AI can see patterns that are essentially invisible to the physician, and potentially critical for the patient.'

AI could ultimately also have a positive impact on the doctor-patient relationship. With access to AI-powered insights, doctors could have more informed conversations with their patients at an early stage in their treatment path, giving them a fuller, data-driven picture of what may lie ahead in terms of treatment and therapy.

What gets me really excited is thinking, 'where is this going to go in the next five or 10 years?'

Esteva is keen to stress that AI will help augment the role of a doctor, not replace it.

'What gets me really excited is thinking, 'where is this going to go in the next five or 10 years?' Unfortunately, many of us can relate to situations where someone we love was given the wrong therapy or misdiagnosed. You end up asking yourself how their lives could have been different if a slightly better decision was made. A single moment can have a ripple effect in a patient's life for years or decades.'

'Physicians should be able to make the best possible decisions based on all available medical knowledge. If you can build AI that can help doctors make the right decisions, by harnessing the collective intelligence of physicians and medical data, that's incredibly powerful.'

Dr. Agus adds, 'AI and machine learning are going to herald a new era, with potential to be applied to diseases beyond cancer and ultimately create better outcomes for patients. It won't happen overnight, and it will be a slow, step-by-step process, but we're embarking on a journey over the next decade to improve every aspect of what we do, through data. That's really exciting.'

Disclaimer

salesforce.com Inc. published this content on 10 December 2020 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 10 December 2020 16:20:03 UTC

View original post here:
AI at Work: How Salesforce AI Could Make Therapeutic Decision-Making for Breast Cancer More Accurate, Affordable and Accessible - marketscreener.com

Recommendation and review posted by Bethany Smith

Pune, India, Dec. 10, 2020 (GLOBE NEWSWIRE) -- The global heparin market size is expected to reach USD 11.43 billion by 2027, exhibiting a CAGR of 3.9% during the forecast period. The market size stood at USD 8.39 billion in 2019. The increasing cases of cardiovascular diseases such as deep vein thrombosis & pulmonary embolism are expected to spur demand for heparin in the forthcoming years, states Fortune Business Insights, in a report. The market size in North America stood at USD 4.28 billion in 2019. The growth in the region is attributed to the prevalence of cardiovascular diseases such as pulmonary embolism. The higher adoption of advanced heparin products will have an excellent effect on the market in the region.

Key Development:

May 2019: Pfizer, Inc. announced that it has received the approval from the U.S. FDA for the administration of its heparin product offering, Fragmin to minimize the recurrence of symptomatic venous thromboembolism (VTE) in pediatric patients aged one month and above.

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Rising Incidence of Chronic Disorders to Incite Business Development

The increasing prevalence of cardiovascular diseases around the world, including heart attacks and strokes will spur opportunities for the market. As per the American Heart Association (AHA) Heart Disease and Stroke Statistics, an estimated 5.3 million Americans suffered from atrial fibrillation in 2019.

The growing demand for heparin among patients can have an excellent impact on the market. As per the Centers for Disease Control and Prevention, coronary heart disease is the most common type of heart disease, killing 365,914 people in 2017.4. About18.2 million adultsage 20 and older have CAD (about 6.7%). Moreover, 2 in 10 deaths from CAD happen in adults less than 65 years old. The increasing awareness about the benefits of heparin in the treatment and management of heart diseases will improve the prospects of the market in the foreseeable future.

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Minimal Impact on the Market During COVID-19

The limitations on non-essential medical procedures and consultations has had a drastic impact on the global market amid COVID-19. The healthcare industry has observed a decline in other medical services besides coronavirus. The increased emphasis on COVIDs vaccine has reduced the demand for other therapeutics.

Furthermore, the lack of supply and production of heparin will simultaneously limit the scope of the market. However, government initiatives, including heavy investments and free medical aid will influence the healthy growth of the market in the time of the pandemic.

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High Adoption of Advanced Products to Boost Market in North America

The market size in North America stood at USD 4.28 billion in 2019. The growth in the region is attributed to the prevalence of cardiovascular diseases such as pulmonary embolism. The higher adoption of advanced heparin products will have an excellent effect on the market in the region.

The increasing healthcare expenditure is expected to foster the healthy growth of the market in North America. The presence of major companies can further enhance the development of the market in the region. Europe is expected to hold the largest share owing to the acceptance of technologically advanced products in the region. The rising number of patients suffering from a range of cardiovascular diseases will further spur opportunities in the region.

Asia Pacific is expected to experience a rapid growth rate owing to the growing patient population. The surging healthcare expenditure in the developing nations will have a tremendous effect on the market in Asia Pacific.

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The Report Lists the Key Companies in the Heparin Market:

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Heparin Market to Hit USD 11.43 Billion with a CAGR of 3.9% by 2027; Rising Prevalence of Chronic Diseases to Propel Business, states Fortune Business...

Recommendation and review posted by Bethany Smith

Dublin, Dec. 08, 2020 (GLOBE NEWSWIRE) -- The "Prostate Cancer Disease Coverage Forecast and Market Analysis to 2036" report has been added to ResearchAndMarkets.com's offering.

Newly approved therapies for castration-resistant prostate cancer are set to create a shift in the way that the disease is treated, while creating a competitive environment for new market entrants.

Latest Key Takeaways

The report estimates that in 2018, there were 1.3 million incident cases of prostate cancer worldwide in males aged 40 years and older, and forecasts that number to increase to 1.5 million cases by 2027.

In the US, prostate cancer is the most common non-cutaneous malignancy diagnosed in men, and is the second-leading cause of cancer mortality in men behind lung cancer.

The overall likelihood of approval of a Phase I prostate cancer asset is 4.9%, and the average probability a drug advances from Phase III is 51.5%. Prostate cancer drugs, on average, take 9.0 years from Phase I to approval, compared to 9.5 years in the overall oncology space.

Pfizer's next-generation androgen receptor (AR) inhibitor Xtandi is the market leader in prostate cancer due to its established efficacy across prostate cancer segmentations and a lack of near-term generic competition. Bolstered by recent and planned expansions into additional prostate cancer segments, Xtandi will continue to be the leading option in this indication. Future expansion opportunities include potential use in combination with PARP inhibitors Talzenna or Rubraca in metastatic castration-resistant prostate cancer (mCRPC) patients.

Xtandi is also being trialed in combination with leuprolide in the Phase III EMBARK study for non-metastatic hormone-sensitive prostate cancer patients progressing on definitive therapy. Potential expansion into this segment represents a significant opportunity to improve outcomes earlier in the treatment paradigm, but the combination will have to demonstrate a significant benefit over existing localized treatment options to justify the additional clinical and financial toxicity of Xtandi treatment.

Since the launch of generic abiraterone in the US in November 2018, sales of Johnson & Johnson's cytochrome P450c17 inhibitor Zytiga have begun to erode. Further generic erosion is expected in the EU and Japanese markets in the next few years, decimating sales of the multi-blockbuster. Although branded Zytiga will continue to decrease in market share, use of abiraterone as part of standard regimens will continue and may expand to include several novel combinations.

The PARP inhibitors Rubraca and Lynparza were both approved in the US in May 2020 for the treatment of mCRPC patients following AR inhibitor therapy. Rubraca received accelerated conditional approval in mCRPC with a deleterious BRCA mutation (germline and/or somatic), while Lynparza received full approval for use in the broader homologous recombination deficient (HRD) population. To potentially differentiate the PARP assets, both are being trialed in the first-line setting of mCRPC; Rubraca in combination with Xtandi against Xtandi alone, and Lynparza with abiraterone against abiraterone alone. There is potential synergy with these combinations as its hypothesized that AR inhibitors may sensitize tumors to PARP treatment by reducing DNA damage repair (DDR) expression.

Late-phase PARP inhibitors Zejula and Talzenna are also being developed in combination with next-generation treatments and will join a crowded PARP treatment space. Zejula is being tested in combination with abiraterone against abiraterone alone as first-line therapy for mCRPC patients. Similarly, Talzenna is being studied in combination with physician's choice of Xtandi or enzalutamide in mCRPC patients, also as a first-line option. The potential synergy of the PARP inhibitors with AR modulators is promising, but a strong benefit will have to be seen to justify use in the front-line setting of mCRPC. If approved, it is likely that these regimens will be limited to the HRD or even BRCA populations, where they will have strong utility but somewhat limited commercial impact due to the relatively small prevalence of these biomarkers.

Next-generation AR inhibitors Nubeqa and Erleada have shifted the treatment paradigm to include these therapies in earlier segments of disease such as non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic hormone-sensitive prostate cancer (mHSPC). Expansion into earlier segments and lines of therapy is ongoing. Bayer is looking to expand Nubeqa's label to include use in very high-risk localized patients and metastatic hormone-sensitive patients. Johnson & Johnson will continue to try and differentiate Erleada with an aggressive development plan that includes potential expansions into chemotherapy-naive mCRPC patients as part of a combination with abiraterone, as well as into the localized setting for patients treated with prostatectomy or radiation therapy.

Akt inhibitors ipatasertib and capivasertib are a potential new mechanistic addition to the prostate cancer space, but the efficacy/tolerability profile of these PI3K/Akt/mTOR pathway inhibitors may prevent approval and potential usage. Ipatasertib is a pan-Akt inhibitor from Roche currently in development for asymptomatic or mildly symptomatic mCRPC patients with PTEN loss as part of a combination with abiraterone. PTEN loss is not a standard target in this indication, but represents a significant market opportunity as it is estimated to occur in approximately 20% of primary prostate cancers and up to 50% of castration-resistant tumors. However, ipatasertib is beset by known class toxicities of PI3K/Akt/mTOR pathway inhibitors such as diarrhea, rash, and ALT/AST elevations that could be detrimental to its regulatory chances. AstraZeneca's Akt inhibitor capivasertib has also demonstrated mixed results in prostate cancer.

In the Phase I/II ProCAID trial, capivasertib in combination with docetaxel failed to meet the primary endpoint of improved progression-free survival in mCRPC patients. However, the combination did improve overall survival in these patients irrespective of PI3K/Akt/mTOR pathway mutations. This has led to initiation of the Phase III CAPItello-281 trial testing capivasertib in combination with abiraterone in de novo mHSPC with PTEN loss.

Several checkpoint inhibitors are in development for prostate cancer, but late-phase data from ongoing combination trials are needed to fully determine their relative outlook in the indication. Merck is pursuing an aggressive late-phase development strategy for Keytruda in prostate cancer that includes combinations with Lynparza, Xtandi, and docetaxel for the treatment of mCRPC patients. Opdivo is also in late-phase development as part of a combination with docetaxel in mCRPC patients after failure on a next-generation hormone therapy. Finally, Roche's Tecentriq, the lone anti-PD-L1 antibody in late-phase development for prostate cancer, is currently in Phase III development in combination with Xtandi or in combination with Cabometyx in mCRPC patients after failing on a next-generation hormone therapy.

Myovant's relugolix is a GnRH receptor antagonist that is differentiated from available GnRH antagonist Firmagon by its oral formulation, which will facilitate use in patients undergoing localized definitive therapy who also need ADT and may also allow use of an intermittent ADT option in advanced hormone-sensitive patients looking to mitigate side effects and maintain quality of life.

Key Topics Covered:

OVERVIEW

DISEASE BACKGROUND

TREATMENT

EPIDEMIOLOGY

MARKETED DRUGS

PIPELINE DRUGS

KEY REGULATORY EVENTS

PROBABILITY OF SUCCESS

LICENSING AND ASSET ACQUISITION DEALS

CLINICAL TRIAL LANDSCAPE

DRUG ASSESSMENT MODEL

MARKET DYNAMICS

FUTURE TRENDS

CONSENSUS FORECASTS

RECENT EVENTS AND ANALYST OPINION

KEY UPCOMING EVENTS

KEY OPINION LEADER INSIGHTS

BIBLIOGRAPHY

APPENDIX

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Global Prostate Cancer Disease Coverage Forecast and Market Analysis 2020-2036 - Xtandi will Remain the Best-selling Therapy Over the Next Decade -...

Recommendation and review posted by Bethany Smith

Autologous hematopoietic stem cell transplant (AHSCT) induces a reduction in relapse rate and physical disability in patients with relapsing-remitting multiple sclerosis (RRMS) who respond inadequately to other treatments, a small study suggests.

The study, Selective cognitive dysfunction and physical disability improvement after autologous hematopoietic stem cell transplantation in highly active multiple sclerosis, was published in the journal Nature Scientific Reports.

AHSCT is an experimental approach to treat multiple sclerosis (MS) that is meant to rebuild a patients immune system in order to stop attacks on the brain and spinal cord.

The procedure begins with collecting a patients own (meaning autologous) healthy hematopoietic stem cells immature cells that can develop into all types of blood cells from the bone marrow. These cells are put back into the patient after a fairly non-aggressive combination of chemotherapy is given to kill the patients immune cells.

A team of researchers at the Vilnius University, in Lithuania, evaluated the effectiveness and safety of the AHSCT procedure in 24 patients (18 female, mean age 37.8 years) with highly active RRMS (mean disease duration of 8.6 years) who failed to respond to conventional therapies.

The aim of the study was to assess cognitive dysfunction and physical disability after AHSCT, to explore the potential factors influencing disability regression after the transplant, and to estimate the safety of low-dose immunosuppressive therapy in highly active relapsing MS patients.

Researchers assessed participants disability and cognition through changes in several functional measures, including the expanded disability status scale (EDSS) and the Brief International Cognitive Assessment for MS, which includes three cognitive domains measured by the symbol digit modalities test, brief visuospatial memory test revised, and California verbal learning test second edition.

Of the 24 patients, 13 (54.2%) completed a 24-month follow-up and were included in the efficacy analysis of AHSCT. From those, two (15.4%) had one relapse during the first year after AHSCT and three patients (23.1%) had one relapse during the second year after AHSCT.

The annualized relapse rate (ARR) was 2.7 one year before AHSCT and 1.9 at two years before AHSCT. After the AHSCT procedure, ARR dropped to 0.2 in the first year and to 0.3 in the second year. This represented an 89% reduction in ARR, when comparing the values at two years after AHSCT with those at two years before AHSCT.

The researchers also noted a reduction in disability progression (as measured by EDSS scores), with 84.6% of patients improving their disability score after AHSCT at month six and 76.9% at one year. Additionally, 76.9% of patients showed stable disability scores two years after the transplant.

The findings of EDSS improvement in almost 85% of the patients suggest that disability may be often at least temporarily reversible in patients with highly active [relapsing] MS if they receive suitable and well-timed treatment, the researchers wrote.

Using appropriate statistical models, researchers found that the clinical variable that explained the disability regression at months 6 and 12 after AHSCT was the disability progression over 6 months before AHSCT.

Improvements in cognition after AHSCT also were observed. Specifically, the scores of information processing speed and verbal learning, measured by the symbol digit modalities test, were significantly higher at month 12 after AHSCT (56.8) when compared to month three (48.3).

The score of brief visuospatial memory test revised that assesses visuospatial memory was slightly lower at month three (25.6) than before AHSCT (27.8), however, the difference was not significant.

The score of the California verbal learning test, which assesses verbal learning, was significantly higher at month 12 (63.6) than before AHSCT (55.2).

No new or active lesions were found on MRI after AHSCT, suggesting that all patients remained without radiological disease activity.

Furthermore, regarding safety, the incidence and severity of adverse events (side effects) after AHSCT were in the expected range and all were resolved. There were no transplant-related deaths reported.

Researchers noted several limitations to the studys findings, including the low sample size and the fact that the patientss assessment and follow-ups were provided at the same center without a comparative group.

Nonetheless, the outcomes are highly promising, as compared to conventional MS treatment, the researchers wrote. Further research is needed to replicate these findings and to assess long-term outcomes and safety of AHSCT.

Diana holds a PhD in Biomedical Sciences, with specialization in genetics, from Universidade Nova de Lisboa, Portugal. Her work has been focused on enzyme function, human genetics and drug metabolism.

Total Posts: 1,053

Patrcia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

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Stem Cell Transplant Reduces Relapses and Disability in RRMS... - Multiple Sclerosis News Today

Recommendation and review posted by Bethany Smith

Our goal with omidubicel is to revolutionize the field of bone marrow transplantation and bring a potentially curative cell therapy option to thousands of patients who are in need of a bone marrow transplant, but lack a suitable stem cell donor. These results bring us one step closer towards that goal, said Julian Adams, Ph.D., chief executive officer of Gamida Cell. Whats more, transplantation with omidubicel has been shown to result in more rapid neutrophil engraftment, a decrease in the amount of time patients spend in hospital, and a reduction in infections. These are very meaningful outcomes for patients and may also lessen the financial costs of certain aspects of the transplant.

Gamida Cell previously reported top-line data for omidubicel. In October, the company reported that the omidubicel phase 3 study achieved its secondary endpoints, analyzed in all randomized patients (intent-to-treat). In May, Gamida Cell reported that the study achieved its primary endpoint, demonstrating a highly statistically significant reduction in time to neutrophil engraftment, a key milestone in a patients recovery from a bone marrow transplant.

These pivotal data form the basis of a Biologics License Application (BLA) that Gamida Cell expects to initiate on a rolling basis before the end of this year. Gamida Cell is preparing to be launch ready in anticipation of potential FDA approval as early as the fourth quarter of 2021, subject to ongoing FDA discussions on manufacturing, quality and other matters.

The live event will be available here. More information about the Phase 3 study of omidubicel and the other updates included in this release can be found in the Pipeline Deep Dive presentation on the Gamida Cell website immediately following the event.

Details of Phase 3 Endpoints

As previously reported, Gamida Cell achieved positive topline results from its Phase 3 clinical study evaluating the safety and efficacy of omidubicel. The median time to neutrophil engraftment was 12 days for patients randomized to omidubicel compared to 22 days for the comparator group (p<0.001). Neutrophil engraftment is a measure of how quickly the stem cells a patient receives in a transplant are established and begin to make healthy new cells, and rapid neutrophil engraftment has been associated with fewer infections and shorter hospitalizations.

Today, Gamida Cell announced the details of achieving all three of the prespecified secondary endpoints of the study, analyzed in all randomized patients (intent-to-treat). These secondary endpoints were the proportion of patients who achieved platelet engraftment by day 42, the proportion of patients with grade 2 or grade 3 bacterial or invasive fungal infections in the first 100 days following transplant, and the number of days alive and out of the hospital in the first 100 days following transplant. All three secondary endpoints demonstrated statistical significance in an intent-to-treat analysis.

Additionally, Gamida Cell reported that the exploratory endpoints in the study demonstrated a reduction in the cumulative incidence of viral infections.

The international, multi-center, randomized Phase 3 study for omidubicel was designed to evaluate the safety and efficacy of omidubicel in patients with hematologic malignancies undergoing allogeneic bone marrow transplant compared to a comparator group of patients who received a standard umbilical cord blood transplant.

The company anticipates reporting the full data set in a peer-reviewed setting in the first half of 2021.

Commercial Readiness

The company discussed the market potential for omidubicel and launch plans. These included quantifying the market opportunity and keys aspects for a successful launch.

As it prepares for the potential commercial launch of omidubicel, the company also announced plans for the Gamida Cell Assist program, which has been designed to focus on patient access and support of every individual and their caregiver at each step of the transplant process. Once the program is launched, the Gamida Cell Assist case management team would provide a consistent, single point of contact for patients and health care professionals. This team would work with the transplant center to track each individual patients omidubicel therapy and provide real-time updates on the status of the therapy. Gamida Cell Assist is also designed to provide additional services, including coverage and reimbursement support, and patient and caregiver support, which may include financial, travel, and lodging assistance.

At Gamida Cell we are inspired to cure, with the goal of pioneering new standards of care for patients with blood cancers and serious blood diseases, said Michele Korfin, chief operating and chief commercial officer of Gamida Cell. The transplant process can be challenging and complex for the patient, caregivers and the entire transplant care team. As we prepare for commercialization, we have developed Gamida Cell Assist to serve as a comprehensive support program to focus on assuring a positive patient experience with omidubicel. We are committed to supporting patients and their caregivers during every step of their journey and enabling what matters most, a successful clinical outcome that makes a meaningful difference for patients.

Update on Natural Killer Cell Therapy GDA-201

In an oral presentation at the recent American Society of Hematology (ASH) 62nd Annual Meeting, it was shown that GDA-201 was well tolerated and no dose limiting toxicities were observed in the Phase 1 clinical study. GDA-201 demonstrated significant clinical activity in patients with non-Hodgkin lymphoma, with 13 complete responses and one partial response observed in 19 patients, for a response rate of 74 percent. Full details of the presentation can be found in the press release.

Phase 2 Study of Omidubicel in Patients with Severe Aplastic Anemia

In a poster presentation at ASH, it was shown that patients with severe aplastic anemia treated with omidubicel achieved sustained early engraftment. These data, which were presented on December 5 by Mohamed Samour, M.D., Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, are the first evidence that omidubicel can result in rapid engraftment and can achieve sustained hematopoiesis in patients who are at high risk for graft failure with conventional umbilical cord blood transplant.

About Omidubicel

Omidubicel is an advanced cell therapy under development as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplant solution for patients with hematologic malignancies (blood cancers). In both Phase 1/2 and Phase 3 clinical studies (NCT01816230, NCT02730299), omidubicel demonstrated rapid and durable time to engraftment and was generally well tolerated.12 Omidubicel is also being evaluated in a Phase 1/2 clinical study in patients with severe aplastic anemia (NCT03173937). The aplastic anemia investigational new drug application is currently filed with the FDA under the brand name CordIn, which is the same investigational development candidate as omidubicel. For more information on clinical trials of omidubicel, please visit http://www.clinicaltrials.gov.

Omidubicel is an investigational therapy, and its safety and efficacy have not been established by the U.S. Food and Drug Administration or any other health authority.

About GDA-201

Gamida Cell applied the capabilities of its NAM-based cell expansion technology to develop GDA-201, an innate natural killer (NK) cell immunotherapy for the treatment of hematologic and solid tumors in combination with standard of care antibody therapies. GDA-201 addresses key limitations of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs of NK cells expanded in culture. GDA-201 is in Phase 1 development through an investigator-sponsored study in patients with refractory non-Hodgkin lymphoma and multiple myeloma.3 For more information on the clinical study of GDA-201, please visit http://www.clinicaltrials.gov.

GDA-201 is an investigational therapy, and its safety and efficacy has not been established by the U.S. Food and Drug Administration or any other health authority.

About the NAM Therapeutic Platform

Gamida Cells proprietary NAM-based cell expansion platform is designed to enhance the number and functionality of donor cells in culture, enabling the creation of potentially transformative therapies that move beyond what is possible with existing approaches. The NAM therapeutic platform leverages the unique properties of nicotinamide to enable the expansion of multiple cell types including stem cells and natural killer (NK) cells with appropriate growth factors to maintain the cells' original phenotype and potency. This can enable the administration of a therapeutic dose of cells with the potential to improve patient outcomes.

About Gamida Cell

Gamida Cell is an advanced cell therapy company committed to cures for patients with blood cancers and serious blood diseases. We harness our cell expansion platform to create therapies with the potential to redefine standards of care in areas of serious medical need. For additional information, please visit http://www.gamida-cell.com or follow Gamida Cell on LinkedIn or Twitter at @GamidaCellTx.

Cautionary Note Regarding Forward Looking Statements

This press release contains forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995, including with respect to timing of initiation and progress of and data reported from the clinical trials of Gamida Cells product candidates, anticipated regulatory filings, launch readiness and FDA approval, commercialization efforts and Gamida Cells expectations regarding its projected ongoing operating activities, which statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to the scope, progress and expansion of Gamida Cells clinical trials and ramifications for the cost thereof; and clinical, scientific, regulatory and technical developments. In light of these risks and uncertainties, and other risks and uncertainties that are described in the Risk Factors section and other sections of Gamida Cells Annual Report on Form 20-F, filed with the Securities and Exchange Commission (SEC) on February 26, 2020, its Reports on Form 6-K filed with the SEC on May 18, 2020, August 11, 2020 and November 10, 2020, and other filings that Gamida Cell makes with the SEC from time to time (which are available at http://www.sec.gov), the events and circumstances discussed in such forward-looking statements may not occur, and Gamida Cells actual results could differ materially and adversely from those anticipated or implied thereby. Any forward-looking statements speak only as of the date of this press release and are based on information available to Gamida Cell as of the date of this release.

______________________1 Horwitz M.E., Wease S., Blackwell B., Valcarcel D. et al. Phase I/II study of stem-cell transplantation using a single cord blood unit expanded ex vivo with nicotinamide. J Clin Oncol. 2019 Feb 10;37(5):367-374.2 Gamida Cell press release, Gamida Cell Announces Positive Topline Data from Phase 3 Clinical Study of Omidubicel in Patients with High-Risk Hematologic Malignancies, issued May 12, 2020. Last accessed August 31, 2020.3 Clinicaltrials.gov identifier NCT03019666

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Gamida Cell Provides Pipeline Update, Including Detailed Results of Pivotal Phase 3 Clinical Study of Omidubicel, and Prepares to Start BLA Submission...

Recommendation and review posted by Bethany Smith

GROUNDBREAKING trial using stem cells on children with acquired brain injuries to begin in Madrid

Three children with an acquired brain injury (ABI) are set to take part in a pioneering stem cell trial that aims to improve their quality of life. Three neurologists at the Nio Jess Hospital in Madrid, the only public hospital in the country which has a dedicated unit for children with ABI, have had real success in using stem cell therapy in adults.

One of the children taking part in the trial in February 2021 is ten-year-old Bruno, who suffered inflammation in the brain when he was four-and-a-half years old that led to him being diagnosed with locked-in syndrome.

The children will begin by receiving an infusion of stem cells through n=bone marrow, which Brunos father hopes will change his boys life.

The doctors are very cautious, they believe that it will give him quality of life and we are going to notice it a lot, he said.

El Nio Jess is the only hospital doing something for acquired brain damage. We are pioneers.And the dream is that this trial becomes a drug, said Brunos mom Macarena

________________________________________________________________________

Thank you for taking the time to read this news article Groundbreaking Trial On Children With Brain Injuries In Madrid. For more UK daily news, Spanish daily news and Global news stories, visit the Euro Weekly News home page.

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Groundbreaking Trial On Children With Brain Injuries In Madrid - Euro Weekly News

Recommendation and review posted by Bethany Smith

- Lower rates of non-relapse transplant related mortality, sepsis, infections, and mucositis reported in patients receiving Iomab-B compared to patients on the control arm receiving salvage therapies

- Iomab-B enables high amounts of radiation to be delivered to the bone marrow to achieve targeted myeloablation

NEW YORK, Dec. 7, 2020 /PRNewswire/ -- Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company") today announced that safety data from its ongoing pivotal Phase 3 SIERRA trial of Iomab-B in patients with relapsed or refractory Acute Myeloid Leukemia (R/R AML) were presented at the 2020 American Society of Hematology (ASH) annual meeting. The oral presentation highlighted Iomab-B's targeting ability and corresponding safety data from 110 patients from the SIERRA trial for which detailed safety data was available. Iomab-B targets CD45, an antigen expressed on leukemia and lymphoma cancer cells and immune cells including bone marrow stem cells but not cells outside of the blood forming or hematopoietic system. This allows high amounts of radiation to be delivered to the bone marrow via Iomab-B while sparing healthy organs. As a result, statistically significant lower rates of sepsis were reported as well as lower rates of febrile neutropenia, mucositis and non-relapse transplant related mortality in patients receiving Iomab-B and bone marrow transplant (BMT) compared to patients that received salvage therapy and a BMT. In addition, patients that crossed over to receive Iomab-B and went to BMT after receiving salvage therapy but not achieving a complete response also had lower rates of sepsis, febrile neutropenia, mucositis and non-relapse transplant related mortality.

Dr. Mark Berger, Actinium's Chief Medical Officer, commented, "We are pleased that the engraftment and safety profile of Iomab-B remains positive and consistent with prior interim safety results at 75% of patient enrollment in SIERRA and also consistent with the large body of historical data from Iomab-B. Collectively, this data gives excitement as we approach the upcoming ad hoc interim analysis for SIERRA that will be completed by year-end and the ultimate potential of Iomab-B for patients with R/R AML and other blood cancers as a targeted conditioning regimen."

Story continues

Safety data presented in ASH oral presentation are highlighted in the table below:

ASH Oral Presentation: High Doses of Targeted Radiation with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] Do Not Correlate with Incidence of Mucositis, Febrile Neutropenia or Sepsis in the Prospective, Randomized Phase 3 Sierra Trial for Patients with Relapsed or Refractory Acute Myeloid Leukemia

Adverse Event

Received Iomab-B/HCT (N=47)1% (N)

No CR Crossed over to Iomab-B/HCT (N=30)2 % (N)

Achieved CR and received Std HCT (N=9) % (N)

Sepsis

4.3 (2)

22.2 (6)

33.3 (3)

Febrile Neutropenia Gr 3-4

34.8 (16)

40.7 (11)

55.6 (5)

Mucositis Gr 3-4

10.9 (5)

18.5 (5)

33.3 (3)

Day +100 Non-Relapse Mortality3

2/45

(4.4%)

3/26

(11.5%)

2/9

(22.2%)

1 Adverse Event data available for 46 of 47 evaluable patients

2 Adverse Event data available for 27 of 30 evaluable patients

3 Iomab-B arm: 4 patients unevaluable. Conventional Care Arm: 4 patients unevaluable

Patient Group

No. of Patients

Radiation dose delivered to the Marrow. Median (range)

Radiation dose to GI tract. Median (range)

Iomab-B

47

14.9 Gy

(4.6-32)

2.8 Gy

(1.6-6.7)

Vijay Reddy, Vice President, Clinical Development and Head of BMT, "The targeted nature of Iomab-B makes it highly differentiated from current BMT conditioning regimens that are largely comprised of non-targeted cytotoxic chemotherapies. These data from SIERRA showing higher rates of sepsis, neutropenia and mucositis in patients receiving chemotherapy are consistent with the literature and unfortunately what we expected but hope to address with Iomab-B. Particularly, chemotherapy's effect on the GI tract and resulting mucositis, which we believe is leading to the higher rates of sepsis seen in the control arm. We are highly encouraged by the lower rates of adverse events and the universal engraftment reported from SIERRA and excited for the potential of targeted conditioning could have an BMT access, patient outcomes and quality of life."

About Iomab-B

Iomab-B (I-131 apamistamab) via the monoclonal antibody apamistamab, targets CD45, an antigen widely expressed on leukemia and lymphoma cancer cells, B cells and stem cells. Apamistamab is linked to the radioisotope iodine-131 (I-131) and once attached to its target cells emits energy that travels about 100 cell lengths, destroying a patient's cancer cells and ablating their bone marrow. By carrying iodine-131 directly to the bone marrow in a targeted manner, Actinium believes Iomab-B will avoid the side effects of radiation on most healthy tissues while effectively killing the patient's cancer and marrow cells.

Iomab-B is currently being studied in the pivotal Phase 3 SIERRA (Study of Iomab-B in Relapsed or Refractory AML) trial, a 150-patient, randomized controlled clinical trial in patients with relapsed or refractory Acute Myeloid Leukemia (AML) who are age 55 and above. The SIERRA trial is being conducted at preeminent transplant centers in the U.S. with the primary endpoint of durable Complete Remission (dCR) at six months and a secondary endpoint of overall survival at one year. Upon approval, Iomab-B is intended to prepare and condition patients for a bone marrow transplant, also referred to as a hematopoietic stem cell transplant, in a potentially safer and more efficacious manner than the non-targeted intensive chemotherapy conditioning that is the current standard of care in bone marrow transplant conditioning. A bone marrow transplant is often considered the only potential cure for patients with certain blood-borne cancers and blood disorders. Additional information on the Company's Phase 3 clinical trial in R/R can be found at http://www.sierratrial.com.

About Actinium Pharmaceuticals, Inc. (NYSE: ATNM)

Actinium Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing ARCs or Antibody Radiation-Conjugates, which combine the targeting ability of antibodies with the cell killing ability of radiation. Actinium's lead application for our ARCs is targeted conditioning, which is intended to selectively deplete a patient's disease or cancer cells and certain immune cells prior to a BMT or Bone Marrow Transplant, Gene Therapy or Adoptive Cell Therapy (ACT) such as CAR-T to enable engraftment of these transplanted cells with minimal toxicities. With our ARC approach, we seek to improve patient outcomes and access to these potentially curative treatments by eliminating or reducing the non-targeted chemotherapy that is used for conditioning in standard practice currently. Our lead product candidate, I-131 apamistamab (Iomab-B) is being studied in the ongoing pivotal Phase 3 Study of Iomab-B in Elderly Relapsed or Refractory Acute Myeloid Leukemia (SIERRA) trial for BMT conditioning. The SIERRA trial is over seventy-five percent enrolled and positive single-agent, feasibility and safety data has been highlighted at ASH, TCT, ASCO and SOHO annual meetings. More information on this Phase 3 clinical trial can be found at http://www.sierratrial.com. I-131 apamistamab will also be studied as a targeted conditioning agent in a Phase 1 study with a CD19 CAR T-cell therapy and in a Phase 1/2 anti-HIV stem cell gene therapy with UC Davis. In addition, we are developing a multi-disease, multi-target pipeline of clinical-stage ARCs targeting the antigens CD45 and CD33 for targeted conditioning and as a therapeutic either in combination with other therapeutic modalities or as a single agent for patients with a broad range of hematologic malignancies including acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma. Ongoing combination trials include our CD33 alpha ARC, Actimab-A, in combination with the salvage chemotherapy CLAG-M and the Bcl-2 targeted therapy venetoclax. Underpinning our clinical programs is our proprietary AWE (Antibody Warhead Enabling) technology platform. This is where our intellectual property portfolio of over 130 patents, know-how, collective research and expertise in the field are being leveraged to construct and study novel ARCs and ARC combinations to bolster our pipeline for strategic purposes. Our AWE technology platform is currently being utilized in a collaborative research partnership with Astellas Pharma, Inc. Website: http://www.actiniumpharma.com

Forward-Looking Statements for Actinium Pharmaceuticals, Inc.

This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time.

Contacts:

Investors:Clayton Robertson Actinium Pharmaceuticals, Inc. crobertson@actiniumpharma.com

Hans Vitzthum LifeSci Advisors, LLCHans@LifeSciAdvisors.com(617) 430-7578

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SOURCE Actinium Pharmaceuticals, Inc.

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Actinium Highlights Iomab-B Safety Data Presented at the 62nd American Society of Hematology Annual Meeting - Yahoo Finance

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