FDA approves first adenoviral vector-based gene therapy for high-risk Bacillus Calmette-Guérin unresponsive non-muscle invasive bladder cancer

• December 19, 2022
• Drugs

On December 16, 2022, the Food and Drug Administration approved nadofaragene firadenovec-vncg (Adstiladrin, Ferring Pharmaceuticals) for adult patients with high-risk Bacillus Calmette-Guérin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

Efficacy was evaluated in Study CS-003 (NCT02773849), a multicenter, single-arm trial enrolling 157 patients with high-risk NMIBC, 98 of whom had BCG-unresponsive CIS evaluable for response. Patients received nadofaragene firadenovec-vncg 75 mL intravesical instillation (3 x 1011 viral particles/mL [vp/mL]) once every three months up to 12 months, unacceptable toxicity, or recurrent high-grade NMIBC. Patients without high-grade recurrence were allowed to continue nadofaragene firadenovec-vncg every three months.

The major efficacy outcome measures were complete response (CR) at any time and duration of response (DoR). CR was defined as negative cystoscopy with applicable transurethral resection of bladder tumor (TURBT) and biopsies and urine cytology. Random bladder biopsies of five sites were conducted in patients remaining in CR at 12 months. The CR rate was 51% (95% CI: 41%, 61%), the median DoR was 9.7 months (range: 3, 52+), and 46% of responding patients remained in CR for at least one year.

The most common adverse events (incidence ≥10%), including laboratory abnormalities (>15%), were increased glucose, instillation site discharge, increased triglycerides, fatigue, bladder spasm, micturition urgency, increased creatinine, hematuria, decreased phosphate, chills, dysuria, and pyrexia.

The recommended nadofaragene firadenovec-vncg dose is 75 mL at a concentration of 3 x 1011 vp/mL instilled once every three months into the bladder via a urinary catheter. Premedication with an anticholinergic is recommended prior to each instillation.

View full prescribing information for Adstiladrin.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted fast-track, breakthrough therapy, and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.