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.