FDA Approval Summary: Nadofaragene Firadenovec-vncg for Bacillus Calmette-Guérin-Unresponsive Non-Muscle-Invasive Bladder Cancer.

On December 16, 2022, the FDA approved the adenoviral vector-based gene therapy nadofaragene firadenovec-vncg (brand name Adstiladrin) for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). The product represents the first approved adenoviral vector-based gene therapy and the first approved gene therapy for bladder cancer. Determination of efficacy was based on results from Study rAd-IFN-CS-003 (Study CS-003), a single-arm trial in 98 evaluable patients with BCG-unresponsive NMIBC with CIS who received intravesical instillations of the gene therapy product (75 mL of nadofaragene firadenovec at 3 × 1011 viral particles per mL) once every 3 months. The major efficacy outcome measures were complete response (CR) at any time and duration of response. Fifty subjects experienced CR 3 months after the initial treatment (CR = 51%; 95% confidence interval, 40.7; 61.3%), of whom 46% remained in response for ≥12 months. The median duration of response was 9.7 months (range: 3-52+). Common adverse reactions included instillation site discharge, fatigue, bladder spasm, micturition urgency, hematuria, chills, pyrexia, and dysuria. The approval of nadofaragene firadenovec provides a new therapy option for patients with BCG-unresponsive NMIBC with CIS who are ineligible for cystectomy.