WASHINGTON--(BUSINESS WIRE)--FerGene, a new gene therapy company formed by Ferring Pharmaceuticals and Blackstone Life Sciences, announced today positive results from the pivotal Phase 3 clinical trial evaluating nadofaragene firadenovec (rAd-IFN/Syn3), an investigational gene therapy, for the treatment of high-grade, Bacillus Calmette-Gurin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC). FKD Therapies Oy (FKD) has led the development and regulatory filing of nadofaragene firadenovec, which has been studied in 33 centers across the U.S. in collaboration with the Society of Urologic Oncology Clinical Trials Consortium (SUO-CTC). The results were presented during the bladder cancer session at the Society of Urologic Oncology 20th Annual Meeting in Washington D.C.

The Phase 3 study of 157 patients from the U.S. met its primary endpoint with 53% of CIS Ta/T1 patients (carcinoma in situ; bladder cancer that is confined to the superficial layer, with or without concomitant high-grade Ta or T1 papillary disease) achieving a CR at three months, and 24% continuing to show a CR at 12 months. Moreover, the study also demonstrated broad efficacy in this difficult to treat patient population with a 73% HGRF survival in patients with papillary disease at three months and 44% HGRF survival at 12 months. In the study, nadofaragene firadenovec was instilled directly into the patients bladder every three months. All responses at 12 months were confirmed by protocol-mandatory five-point biopsies.

Bladder cancer is one of the most frequently occurring cancers with an estimated 699,450 people living with bladder cancer and more than 80,000 new cases diagnosed each year in the U.S. alone.1 In high-grade NMIBC patients, BCG is the standard treatment, and, although effective, over 60% of these tumors eventually re-occur. 2,3

Currently, patients living with high-grade NMIBC who are unresponsive to BCG have few treatment options and often face bleak outcomes, including complete bladder removal, known as cystectomy, said Colin P. N. Dinney, MD, Professor and Chairman of the Department of Urology at The University of Texas M.D. Anderson Cancer Center. Cystectomy is a complex and life-altering surgical procedure for patients, so these positive results from the Phase 3 trial of nadofaragene firadenovec are highly promising for patients. It would be gratifying to provide an alternative that addresses the critical unmet need for effective second-line therapy for patients facing radical cystectomy.

Efficacy Analysis*

AssessmentPeriod

CIS Ta/T1 Disease (n=103) CR(% [n])

High-Grade Ta/T1 Papillary Disease (non CIS)

(n=48) HGRF Survival (% [n])

Month 3

53.4% (55)

72.9% (35)

Month 6

40.8% (42)

62.5% (30)

Month 9

35.0% (36)

58.3% (28)

Month 12

24.3% (25)

43.8% (21)

*151 patients

In the Phase 3 trial, the most common adverse events (AEs) included fatigue, bladder spasm and discharge around the catheter, micturition urgency, hematuria, chills, fever, headache, painful urination, urinary tract infection, and diarrhea. No grade 4 or 5 treatment-related AEs were reported in the study. Study drug-related AEs were transient and local in nature, with a median duration of less than two days, with the exception of fatigue, which had a median duration of 11 days and urinary frequency which had a median duration of 41 days. There was a 1.9% percent rate of discontinuations due to study drug-related AEs.

We are pleased with these Phase 3 data results, including the complete response rates and favorable safety profile seen with nadofaragene firadenovec, said Nigel R. Parker4, PhD, of FKD Therapies Oy. These data were part of our submission package to the FDA, and we look forward to continuing to work with the agency to potentially bring nadofaragene firadenovec to patients with BCG unresponsive disease.

As a practicing urologist and trial investigator, its encouraging to see these types of efficacy and safety results in patients with high-grade NMIBC, an area thats been in need of new innovative treatment options for more than 20 years, said Neal Shore, MD, FACS, Medical Director, Carolina Urologic Research Center. These robust clinical results further demonstrate the potential of nadofaragene firadenovec as a valuable treatment option for NMIBC patients.

The U.S. Food and Drug Administration (FDA) has validated FKDs Biologics License Application (BLA) and granted Priority Review for nadofaragene firadenovec, which previously received Fast Track and Breakthrough Therapy Designations.

About nadofaragene firadenovec

Nadofaragene firadenovec (rAd-IFN/Syn3) is an investigational gene therapy being developed as a treatment for patients with high-grade, BCG unresponsive, NMIBC. It is an adenovirus vector-based gene therapy containing the gene interferon alfa-2b, administered by catheter into the bladder every three months. The vector enters the cells of the bladder wall, where, it breaks down, releasing the active gene to do its work. The internal gene/DNA machinery of the cells picks up the gene and translates its DNA sequence, resulting in the cells secreting high quantities of interferon alfa-2b protein, a naturally occurring protein the body uses to fight cancer. This novel gene therapy approach thereby turns the patient's own bladder wall cells into multiple interferon microfactories, enhancing the body's natural defenses against the cancer.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

NMIBC is an early form of bladder cancer which is present in the superficial layer of the bladder and has not invaded deeper into the bladder or spread to other parts of the body.5 It is estimated that there will be 80,000 new cases of bladder cancer in the U.S. in 2019; more than 70% of these cases present as NMIBC.2,6 In patients with high-grade NMIBC, intravesical BCG is the recommended treatment; however, between 30% and 50% cases with high-grade disease will recur.7 The outcome for BCG unresponsive patients is poor, with total cystectomy (complete removal of the bladder) often being the next treatment option.8

About FerGene

FerGene, a new gene therapy company and Ferring subsidiary, has been created to potentially commercialize nadofaragene firadenovec in the U.S. and to advance the global clinical development. FerGenes goal is to bring this promising therapy to a patient population which has seen little improvement in their standard of care over the past twenty years. Blackstone Life Sciences will invest $400 million USD and Ferring will invest up to $170 million USD in FerGene. Ferring will also potentially launch and commercialize nadofaragene firadenovec outside of the U.S.

About FKD Therapies Oy

FKD Therapies Oy is a specialist gene therapy company based in Kuopio, Finland originally conceived by scientific and medical founders, Dr Nigel R Parker and Professor Seppo Yla-Herttuala4, for the specific purpose of undertaking the development of adenovirus mediated interferon alfa-2b. FKD has led the overall development of nadofaragene firadenovec through manufacturing at FinVector Oy, late stage clinical trials and the current BLA filing. FinVector Oy and FKD Oy are part of the Trizell Group.

About Ferring Pharmaceuticals

Ferring Pharmaceuticals is a research-driven, specialty biopharmaceutical group committed to helping people around the world build families and live better lives. Headquartered in Saint-Prex, Switzerland, Ferring is a leader in reproductive medicine and maternal health, and in specialty areas within gastroenterology and urology. Founded in 1950, Ferring now employs approximately 6,500 people worldwide, has its own operating subsidiaries in nearly 60 countries and markets its products in 110 countries.

1 National Cancer Institute. Cancer Stat Facts: Bladder Cancer. Available at: https://seer.cancer.gov/statfacts/html/urinb.html. Last accessed: December 2019.

2 Maruf, M et al., Non invasive bladder cancer: a primer on immunotherapy. Cancer Biol Med. 2016;13(2):194-205.

3 Derr, L et al., Intravesical Bacillus Calmette Guerin Combined with a Cancer Vaccine Increases Local T-Cell Responses in Non-muscle-Invasive Bladder Cancer Patients. Clin Cancer Res. 2017;23(3):717-725.

4 AIV Institute for Molecular Sciences, Kuopio, Finland.

5 Anastasiadis A, de Reijke TM. Best practice in the Treatment of Nonmuscle Invasive Bladder Cancer. Ther Adv Urol. 2012;4(1):13-32

6 Ghatalia, Pooja et al. Approved checkpoint inhibitors in bladder cancer: which drug should be used when?. Therapeutic advances in medical oncology vol. 10 1758835918788310. 30 Jul. 2018, doi:10.1177/1758835918788310.

7 Cambier S et al. EORTC Nomograms and Risk Groups for Predicting Recurrence, Progression, and Disease-specific and Overall Survival in NonMuscle-invasive Stage TaT1 Urothelial Bladder Cancer Patients Treated with 13 Years of Maintenance Bacillus Calmette-Gurin. European Urolology. 2016, Vol. 69(1): 60-69.

8 Cookson, M et al.,Use of intravesical valrubicin in clinical practice for treatment of nonmuscle-invasive bladder cancer, including carcinoma in situ of the bladder. Therapeutic Advances in Urology. 2014, Vol. 5(5):181-191.

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FerGene Announces Pivotal Phase 3 Study of Nadofaragene Firadenovec Met Its Primary Endpoint With More Than Half of Patients With High-Grade...

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