Half the patients in the pivotal trial saw their bladder cancer disappear. That was the headline result behind the FDA’s December 16, 2022 approval of nadofaragene firadenovec-vncg, sold as Adstiladrin, for adults with high-risk bladder cancer that no longer responds to BCG therapy.
The agency called it the first gene therapy for the disease. It is also the first approved adenoviral vector-based gene therapy of any kind. The indication covers non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ, with or without papillary tumors. Ferring Pharmaceuticals holds the approval.
What the trial showed
The decision rested on Study CS-003, an open-label, multicenter, single-arm phase 3 trial. Safety was assessed in 157 enrolled patients, and 98 of them could be evaluated for response. Fifty of those 98 had a complete response, a rate of 51%, meaning cystoscopy, biopsied tissue and urine showed no remaining signs of cancer. The median duration of response was 9.7 months. Of those who responded, 46% stayed in complete response for at least a year.
Patients got 75 mL of the therapy instilled into the bladder once every three months, for up to 12 months or until toxicity became intolerable or high-grade disease returned. Those with no recurrence could stay on treatment. Before the first dose, every patient had a transurethral resection of bladder tumor to clear all resectable disease. People with muscle-invasive or metastatic urothelial carcinoma were left out.
Among the evaluable patients, the median age was 70. A third of them, 32%, were older than 75. Eighty-eight percent were male and 92% were White.
Side effects
Serious toxicities hit 11% of patients. Coronary artery disease and hematuria were the ones that occurred in more than 1%. Adverse reactions forced 1.9% of patients to stop for good, and 34% needed a dose interruption.
The most common reactions, each reported by more than 10% of patients, were instillation site discharge (33%), fatigue (24%), bladder spasm (20%), micturition urgency (19%), hematuria (17%), chills (16%), dysuria (16%) and pyrexia (15%). Lab results worsened in some patients too, with higher glucose in 38%, higher triglycerides in 30% and higher creatinine in 17%. Phosphate fell in 16% and hemoglobin in 16%.
What doctors said
“This approval provides healthcare professionals with an innovative treatment option for patients with high-risk non-muscle invasive bladder cancer that is unresponsive to BCG therapy,” said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research. “Today’s action addresses an area of critical need.”
Steven A. Boorjian, chair of urology at Mayo Clinic and lead investigator on a recent trial of the therapy, pointed to the old limits. “Patients with BCG-unresponsive NMIBC have historically had limited treatment options other than bladder removal surgery,” he said.
The FDA had granted the application priority review, breakthrough therapy, fast track and orphan drug designations. The European Union approved the drug in May 2026.
Sources
- Nadofaragene firadenovec – Wikipedia
- FDA Approves Nadofaragene Firadenovec for High-risk Non–Muscle Invasive Bladder Cancer | OncLive
- FDA Approval Summary: Nadofaragene firadenovec-vncg for bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer
- Nadofaragene firadenovec
