The development of drugs and gene therapies for rare diseases is costly. It requires significant investments in advanced technology, clinical trials, and regulatory approvals. But what happens when the development of such gene therapies is paused once they are no longer commercially viable?

A few weeks ago, Swiss biopharma Basilea announced it will sell and transfer all rights for the companys glioblastoma candidate lisavanbulin (BAL101553) to the Glioblastoma Foundation for an undisclosed initial purchase cost. The charitable organisation plans to take over lisavanbuilins post-access trial programme, allowing patients from previous clinical studies to continue receiving the drug.

Similarly, in April 2024, Great Ormond Street Hospital (GOSH) in the UK announced that it is attempting to obtain the licence for gene therapy simoladagene autotemcel to treat the rare disease adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCiD) on a non-profit basis. This came after the University College London-spinout Orchard Therapeutics, which planned to bring it to market, dropped out of its development plans. If successful, this will be the first time that an NHS trust has the authorisation to market a drug for this kind of treatment.

ADA-SCiD is a rare genetic disorder marked by a severely deficient immune system due to mutations in the ADA gene, which is crucial for producing the enzyme adenosine deaminase. It causes a severely compromised immune system, leading to recurrent, severe infections, and developmental delays.

Across three clinical trials conducted in the US and UK, 50 patients with ADA-SCiD were treated with simoladagene autotemcel, which was co-developed by labs at UCL and University of California Los Angeles. The overall survival with the gene therapy was 100% in all studies up to 36 months. Event-free survival, defined as no need for enzyme-replacement therapy or rescue allogeneic haematopoietic stem-cell transplantation, reached 97% and 95% at 24 months, respectively, in the two US studies (NCT01852071 and NCT02999984) and 95% in the UK study (NCT01380990).

The gene therapy is currently available to patients in clinical trials, but it is important for these therapies to be approved. Dr. Claire Booth, who leads the ADA-SCiD clinical trial at GOSH, says We want to ensure that these proven treatments can be offered to patients and families quickly and simply, without the need to look at compassionate use approaches.

Access the most comprehensive Company Profiles on the market, powered by GlobalData. Save hours of research. Gain competitive edge.

Your download email will arrive shortly

We are confident about the unique quality of our Company Profiles. However, we want you to make the most beneficial decision for your business, so we offer a free sample that you can download by submitting the below form

Country * UK USA Afghanistan land Islands Albania Algeria American Samoa Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia Bonaire, Sint Eustatius and Saba Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory Brunei Darussalam Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos Islands Colombia Comoros Congo Democratic Republic of the Congo Cook Islands Costa Rica Cte d"Ivoire Croatia Cuba Curaao Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands Faroe Islands Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guam Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and McDonald Islands Holy See Honduras Hong Kong Hungary Iceland India Indonesia Iran Iraq Ireland Isle of Man Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati North Korea South Korea Kuwait Kyrgyzstan Lao Latvia Lebanon Lesotho Liberia Libyan Arab Jamahiriya Liechtenstein Lithuania Luxembourg Macao Macedonia, The Former Yugoslav Republic of Madagascar Malawi Malaysia Maldives Mali Malta Marshall Islands Martinique Mauritania Mauritius Mayotte Mexico Micronesia Moldova Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island Northern Mariana Islands Norway Oman Pakistan Palau Palestinian Territory Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Puerto Rico Qatar Runion Romania Russian Federation Rwanda Saint Helena, Ascension and Tristan da Cunha Saint Kitts and Nevis Saint Lucia Saint Pierre and Miquelon Saint Vincent and The Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and The South Sandwich Islands Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syrian Arab Republic Taiwan Tajikistan Tanzania Thailand Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu Uganda Ukraine United Arab Emirates US Minor Outlying Islands Uruguay Uzbekistan Vanuatu Venezuela Vietnam British Virgin Islands US Virgin Islands Wallis and Futuna Western Sahara Yemen Zambia Zimbabwe Kosovo

Industry * Academia & Education Aerospace, Defense & Security Agriculture Asset Management Automotive Banking & Payments Chemicals Construction Consumer Foodservice Government, trade bodies and NGOs Health & Fitness Hospitals & Healthcare HR, Staffing & Recruitment Insurance Investment Banking Legal Services Management Consulting Marketing & Advertising Media & Publishing Medical Devices Mining Oil & Gas Packaging Pharmaceuticals Power & Utilities Private Equity Real Estate Retail Sport Technology Telecom Transportation & Logistics Travel, Tourism & Hospitality Venture Capital

Tick here to opt out of curated industry news, reports, and event updates from Pharmaceutical Technology.

Submit and download

One of the main challenges associated with developing gene therapies is funding. It is difficult to get funding from venture capital or private investors due to small patient populations and uncertain returns. Grants can fund early clinical trials, but not the full development and approval process, which requires more funding, explains Dr. Donald Kohn, lead investigator of the ADA-SCiD programme at UCLA, and Distinguished Professor, Microbiology, Immunology and Molecular Genetics.

Another huge challenge is the expensive commercial-grade manufacturing costs. Commercial feasibility plays a big role in pharma companies progressing drug development and this may be challenging in ultra-rare diseases with small patient populations. Advanced therapies like gene therapy are costly and complex to produce.

Simoladagene autotemcel is composed of autologous CD34+ haematopoietic stem and progenitor cells (HSPCs) transduced ex vivo with a self-inactivating lentiviral vector encoding human ADA. Lentiviral vector production represents a large portion of the high costs associated with such therapies.

The cost of reagents needed to make a gene therapy product is high, but we hope that this may come down in the future, says Booth.

One company that is trying to tackle high manufacturing costs is Ori Biotech. The biotech, which is headquartered in London, UK and Woodcliff, New Jersey, has developed an automated platform that streamlines the cell therapy manufacturing process.

[Oris] IRO platform takes the most labour-intensive and time-consuming parts: activation, transduction, expansion, and harvest, and automates them into one integrated system without any manual interventions or tubing, said Ori Biotechs CEO Jason Foster.

In doing so, the platform aims to increase throughput, lower cost, and improve reliability by reducing failure rates. Ori has worked with companies like North Carolina-based Inceptor Bio to scale up manufacturing of their chimeric antigen receptor (CAR)-M, CAR-T and CAR-NK programmes. One of its candidates IB-T101 is set to enter clinical trials in Q4 2024.

In addition to funding challenges and manufacturing costs, there might also be differences based on locations in how gene therapies are made accessible to patients, says Kohn. He explained that national healthcare systems, like those in Europe, may have some advantage in funding rare disease gene therapies compared to the US healthcare system that includes multiple private payers. With a single national payer, developers only need to negotiate reimbursement with one entity rather than many private insurers. Additionally, Kohn said national systems can recognise that an initially high-cost therapy might save money over many years if it treats a fatal or chronic rare disease.

Just as a nonprofit hospital like GOSH is attempting to license EFS-ADA, there are other cases of individuals taking matters into their own hands, via an untraditional route. Terry Pirovolakis started Elpida Therapeutics, a not-for-profit biotech, after his son Michael was diagnosed with a rare disease called spastic paraplegia type 50 (SPG50) at five months old.

After Michael received his diagnosis, Pirovolakis said: We were told, Go home, love him. Theres not much we can do. Hell be paralysed from the waist down by the age of 10, quadriplegic by the age of 20. I just couldnt accept that fate for my child.

Elpida, which is set up as a company but operates as a nonprofit, was initially funded with money from philanthropists. Pirovolakis explained that the model works through partnerships with companies, institutions, and hospitals. When the organisation partners with a hospital, the latter agrees to treat a certain number of patients for free, or at a very low cost. In exchange, Elpida gives the hospital a promissory note.

He explains that funds through incentives from the US Food and Drug Administration (FDA) like priority review vouchers (PRV) for a gene therapy product will be used to pay the hospitals, and to hopefully fund more programmes.

Theyre [the hospital] taking on a mutual risk with us knowing that were trying to do good, not just trying to make money, said Pirovolakis.

Elpida aims to use any money it makes after paying the promissory notes to fund more programmes. Earlier this month, Pirovolakis mentioned that the FDA greenlit Elpidas plans to initiate a Phase III study of its lead candidate Melpida for patients with the rare disorder SPG50. Eight children will be dosed in the trial that is set to begin in August 2024. This is off the back of an ongoing Phase I/II (NCT05518188) trial.

Pirovolakis says there can be a socially acceptable way of dealing with the therapies once theyre deemed commercially unviable. Pharma companies want to help find therapies for rare diseases but also need to consider their best interests. So, when they drop it [a therapy], [giving it] to another company, or back to the university.thats an ethical way of doing things.

When they hold it for five or 10 years, looking for a financial partner to recoup their lost assets, that is not the right way of doing things.

Despite the promise of these alternate models, Pirovolakis delivers a stark reminder: Our model isnt ideal; it is out of necessity.

Give your business an edge with our leading industry insights.

Read the original post:
Left in limbo: When pharma halts rare disease research - Pharmaceutical Technology

Comments are closed.