Real-World Outcomes With Nadofaragene in BCG-Unresponsive NMIBC

Physician Summary: Real-World Data on Nadofaragene Firadenovec in BCG-Unresponsive NMIBC

A recent study by Moyer et al (2025) provides real-world data on the efficacy and safety of nadofaragene firadenovec in patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC). Conducted across 3 Mayo Clinic sites between November 2023 and October 2024, the study included 45 patients, with 29 evaluable for efficacy analysis. The median follow-up was 8.2 months.​

Study Design

• Primary End Point: Radiological progression-free survival
• Secondary End Points: Overall survival
• Cohorts:
• Carcinoma in situ (CIS) with or without papillary disease

• Ta/T1 tumors without CIS
• Treatment Regimen: Intravesical nadofaragene firadenovec administered every 3 months​

Topline Results

• Complete Response / High-Grade Recurrence-Free Survival:
• At 3 months: 72%

• At 6 months: 62%
• Cystectomy-Free Survival:
• At 6 months: 94%
• Overall Survival:
• At 6 months: 100%
• Adverse Events:
• Bladder spasms: 62%

• Failure to retain: 31%

• Grade 3 adverse events (eg, fatigue, fever, dizziness): 9%

• No grade 4/5 adverse events reported​

These findings suggest that nadofaragene firadenovec offers promising efficacy and a favorable safety profile for patients with BCG-unresponsive NMIBC. The high cystectomy-free and overall survival rates are particularly noteworthy. However, longer follow-up is necessary to assess the durability of these responses.​

This study contributes valuable real-world evidence to the existing clinical data on nadofaragene firadenovec, supporting its role as a viable treatment option for this patient population.​

Regarding the clinical trial data that led to the approval of nadofaragene firadenovec, the pivotal phase 3 trial (Study CS-003) demonstrated a 53.4% complete response rate at 3 months in patients with BCG-unresponsive CIS.The median duration of response was 9.7 months, with 34.2% of patients maintaining a complete response for at least 36 months. These results underscore the potential of nadofaragene firadenovec as a bladder-sparing option for patients with BCG-unresponsive NMIBC.