The approval follows a CRL that was issued in 2021 due to problems with chemistry, manufacturing, and controls.
The FDA has approved the first gene therapy for the treatment of bladder cancer, according to an announcement from the agency and the drug's manufacturer, Ferring.1,2
Nadofaragene firadenovec-vncg, which will be marketed as Adstiladrin, is a non-replicating adenoviral vector-based gene therapy that is administered intravesically every 3 months. The novel therapy is indicated specifically in adult patients with high-risk, Bacillus Calmette-Guerin-unresponsive non-muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors.
“Ferring has been working diligently to realize the potential of gene therapy for bladder cancer patients, where there has long been a critical unmet need for additional treatment options,” said Armin Metzger, Executive Vice President and Chief Science Officer, Ferring Pharmaceuticals.2 “We are proud to have achieved this critical milestone towards fulfilling the potential of Adstiladrin, a first-of-its-kind therapy, for bladder cancer patients. Adstiladrin is the culmination of a complex research, development, and production process, and we are grateful to the teams, physicians and patients who have helped us reach this approval.”
The gene therapy was evaluated in an open-label phase 3 clinical trial (NCT02773849) that included 157 patients, with a primary end point of complete response rate at 12 months. Previously reported results showed that more than half of patients treated (51%; 95% CI, 41-61) achieved complete response by 3 months. Among those who reached an initial complete response, 46% remained free of high-grade recurrence at 12 months (median duration, 9.7 months).
The most common adverse events included bladder discharge, fatigue, bladder spasm, urinary urgency, hematuria, chills, fever, and pain while urinating. Just under 2% of patients discontinued treatment due to adverse events.
Notably, the therapy was developed as part of a collaboration between Ferring and the Society of Urologic Oncology Clinical Trials Consortium, who defined the clinical trial design to specifically address the unique needs of this patient population.
“Patients with BCG-unresponsive NMIBC have historically had limited treatment options other than bladder removal surgery,” said Steven A. Boorjian, MD, Carl Rosen Professor and Chair of the Department of Urology at Mayo Clinic, and lead investigator on the recent clinical trial of Adstiladrin, in a statement.2 “The approval of Adstiladrin is therefore a significant advance in the current treatment landscape and provides a novel treatment option for patients.”
Ferring said the gene therapy should be available in the US in the latter half of 2023 following expansion of their manufacturing capacity to accomodate commercial-scale vector production.