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

Area of Science:

• Oncology
• Gene Therapy
• Urology

Background:

• High-risk non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) that is unresponsive to Bacillus Calmette-Guérin (BCG) presents a significant treatment challenge.
• Current treatment options for BCG-unresponsive NMIBC with CIS are limited, particularly for patients ineligible for cystectomy.

Purpose of the Study:

• To evaluate the efficacy and safety of nadofaragene firadenovec-vncg (Adstiladrin) in adult patients with BCG-unresponsive NMIBC with CIS.
• To establish Adstiladrin as a novel therapeutic option for this patient population.

Main Methods:

• A single-arm clinical trial (Study CS-003) involving 98 evaluable patients with BCG-unresponsive NMIBC with CIS.
• Patients received intravesical instillations of nadofaragene firadenovec (3 × 10^11 viral particles/mL) every 3 months.
• Efficacy endpoints included complete response (CR) rates and duration of response.

Main Results:

• A complete response (CR) was achieved by 51% of patients (95% CI, 40.7-61.3%) at 3 months post-treatment.
• Of those achieving CR, 46% maintained response for at least 12 months.
• The median duration of response was 9.7 months (range: 3-52+ months).
• Common adverse reactions included fatigue, bladder spasms, and hematuria.

Conclusions:

• Nadofaragene firadenovec-vncg (Adstiladrin) is the first approved adenoviral vector-based gene therapy and the first gene therapy for bladder cancer.
• Adstiladrin provides a new and effective treatment option for patients with BCG-unresponsive NMIBC with CIS who are not candidates for cystectomy.