FDA Approves Nadofaragene Firadenovec-vncg for BCG-Unresponsive NMIBC


Phase 3 study findings have led to the FDA approval of nadofaragene firadenovec-vncg for a subgroup of patients with high-risk Bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer.

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The FDA has granted approval to nadofaragene firadenovec-vncg (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) with or without papillary tumors.1,2

Nadofaragene firadenovec-vncg is a non-replicating adenoviral vector-based gene therapy.

“Patients with BCG-unresponsive NMIBC have historically had limited treatment options other than bladder removal surgery,” said Steven A. Boorjian, MD, Carl Rosen professor and chair of the Department of Urology at Mayo Clinic, and lead investigator on the recent clinical trial of Adstiladria, in a press release. “The approval of [nadofaragene firadenovec-vncg] is therefore a significant advance in the current treatment landscape and provides a novel treatment option for patients.”

Approval of the therapy is based on results from the open-label, multicenter, single-arm, phase 3 Study CS-003 (NCT02773849). Nadofaragene firadenovec-vncg was effective and demonstrated a favorable risk profile in the study.1-3

Complete responses (CRs) to the single intravesical 75 mL dose of nadofaragene firadenovec (3 × 1011 viral particles per mL) were achieved in 51% (95% CI, 41%-61% of patients with carcinoma in situ with or without concomitant high-grade Ta or T1 disease within 3 months, meeting the study’s primary end point. In addition, the median duration of response (DOR) observed with the agent was 9.7 months. Moreover, 46% of the patients who achieved a CR were high-grade recurrence-free at 12 months.3

The most common grade 3/4 drug-related adverse event in the study was micturition, which occurred in 2 patients. Both events were grade 3. No treatment-related deaths occurred during the study.

Study CS-003 included 157 patients with high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumors. Patients were 18 years of age or older with an ECOG performance status of 2 or lower. The study excluded patients who had ad upper urinary tract disease, urothelial carcinoma within the prostatic urethra, lymphovascular invasion, micropapillary disease, or hydronephrosis.

The secondary end points of the study were durability of CR in patients with CIS, rate of event-free survival (EFS), durability of EFS, the incidence of cystectomy in the study, overall survival, anti-adenoviral antibody levels for correlation to response rate, safety, and durability of response during long-term follow-up.

“This approval provides healthcare professionals with an innovative treatment option for patients with high-risk non-muscle invasive bladder cancer that is unresponsive to BCG therapy,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a press release. “Today’s action addresses an area of critical need. The FDA remains committed to facilitating the development and approval of safe and effective cancer treatments.”

1. Ferring receives approval from U.S. FDA for Adstiladrin for high-risk, BCG-unresponsive non-muscle invasive bladder cancer. News release. Ferring Pharmaceuticals. December 16, 2022. Accessed December 19, 2022. https://bit.ly/3YxyWdY
2. FDA Approves first gene therapy for the treatment of high-risk, non-muscle-invasive bladder cancer. News release. FDA.gov. December 16, 2022. Accessed December 19, 2022. https://bit.ly/3HNUI7t
3. Boorjian SA, Alemozaffar M, Konety BR, et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol. 2021;22(1):107-117. doi:10.1016/S1470-2045(20)30540-4
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