ADSTILADRIN® Phase 3 Five-Year Outcomes: Enduring Safety and Bladder Preservation in BCG-Refractory NMIBC

The Phase 3 clinical trial of ADSTILADRIN® (nadofaragene firadenovec-vncg) has reported its final 60-month follow-up data, highlighting the therapy's enduring efficacy and safety profile for treating high-risk non-muscle invasive bladder cancer (NMIBC) that is unresponsive to Bacillus Calmette-Guérin (BCG) treatment. The study, presented at the American Urological Association's 2024 Annual Meeting, revealed an 80% overall survival rate and a significant cystectomy-free survival rate of 49% at the 60-month mark. This represents the most extended follow-up data for a novel agent addressing BCG-unresponsive NMIBC and has been published in The Journal of Urology®.

ADSTILADRIN, approved by the U.S. Food and Drug Administration (FDA), is a groundbreaking intravesical non-replicating adenoviral vector-based gene therapy. It functions by introducing the human interferon-alfa 2b gene (IFNα2b) into the bladder, prompting the secretion of interferon alfa-2b protein every three months with a single treatment. This innovative approach converts bladder wall cells into local producers of interferon, enhancing the body's natural defenses against cancer.

The Phase 3 study included two patient cohorts: one with carcinoma in situ (CIS) along with or without papillary tumors (Ta/T1), and another with high-grade Ta/T1 without CIS. Both groups received ADSTILADRIN treatment quarterly for up to 12 months or until they encountered unacceptable toxicity or experienced a recurrence of high-grade NMIBC. The study protocol did not allow for retreatment after a single dose if a complete response was not achieved at three months.

At the 12-month post-treatment mark, patients underwent a bladder biopsy of five different sites. Those showing no signs of high-grade recurrence continued to receive ADSTILADRIN quarterly, entering a further four-year treatment and monitoring phase. The study demonstrated that ADSTILADRIN is well-tolerated, with the majority of treatment-emergent adverse events being transient and mild, and no new safety concerns were raised during the extended follow-up period.

The 60-month overall survival rate was 76.3% for the CIS cohort and 85.9% for the papillary disease cohort. The cystectomy-free survival rate was 43.2% for the CIS group and 58.7% for the papillary disease group. Importantly, clinical progression to muscle invasion, a severe complication, was observed in only 3.3% of patients over the five-year period.

These findings underscore ADSTILADRIN's potential to preserve bladder function in nearly half of the patients with CIS and in two-thirds of those with high-grade Ta/T1 papillary disease, after five years. This is a significant advancement in the treatment of BCG-unresponsive NMIBC, offering patients an alternative to more radical treatments such as cystectomy. The long-term data further validate the role of gene therapy in managing this type of bladder cancer and provide hope for improved patient outcomes.