On December 16, 2022, the FDA granted approval to nadofaragene firadenovec-vncg (Adstiladrin; Ferring Pharmaceuticals), a nonreplicating adenoviral vector–based gene therapy, for adults with high-risk Bacillus Calmette-Guérin (BCG) unresponsive non–muscle-invasive bladder cancer (NMIBC) and carcinoma in situ, with or without papillary tumors. The FDA granted this indication breakthrough therapy and orphan drug designations.
This approval was based on the results of Study CS-003, a multicenter, single-arm clinical trial of 157 patients with high-risk NMIBC, including 98 patients with BCG-unresponsive carcinoma in situ who were evaluable for response. Patients received nadofaragene firadenovec 75 mL via intravesical instillation (3 × 1011 viral particles/mL) once every 3 months for up to 12 months, until unacceptable adverse events or until recurrent high-grade NMIBC. Patients without high-grade disease recurrence continued to receive nadofaragene firadenovec every 3 months.
The major efficacy measures were a complete response (CR) at any time and the duration of response (DOR). Random bladder biopsies of 5 sites were done in patients with a CR at 12 months. The CR rate was 51% (95% confidence interval, 41%-61%) and the median DOR was 9.7 months (range, 3-≥52); 46% of the responding patients had a sustained CR for at least 1 year.
The most common (≥10%) adverse events, including laboratory abnormalities (>15%), were elevated glucose level, instillation site discharge, increased triglycerides, fatigue, bladder spasm, micturition urgency, increased creatinine, hematuria, decreased phosphate, chills, dysuria, and pyrexia.