Efficacy and Safety of Nadofaragene Firadenovec Hold Up in NMIBC Real-World Study

Early real-world data support the efficacy and safety of nadofaragene firadenovec-vncg (Adstiladrin) following the intravesical therapy’s December 2022 FDA approval for patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC), as all patients were alive at a median follow-up of 8.2 months and the cystectomy-free survival (CFS) rate was 95%.1,2

Findings from the real-world study were presented at the 2025 Genitourinary Cancers Symposium and showed that 79% of evaluable patients with carcinoma in situ (CIS) with or without papillary disease (n = 24) achieved a complete response (CR) at 3 months.2 Additionally, at a median follow-up of 7.3 months, 84% of responders maintained CRs. The median duration of response (DOR) was not reached, and Kaplan Meier–estimated DORs were 100% at 6 months and 75% at 9 months.

Among patients with papillary-only disease (n = 19), 68% were recurrence-free at 3 months and at a median follow-up of 8.9 months, 77% remained recurrence-free. Overall, 3 patients in the study experienced disease progression from Ta to T1, CIS to T2, and Ta to metastatic.

“Promising clinical CR rates and a tolerable adverse effect [AE] profile in patients with BCG-unresponsive NMIBC [were observed],” Jacob Moyer, BS, of Mayo Clinic, and coauthors wrote in a poster presentation of the real-world study findings. “Larger multicenter studies with extended follow-up will be valuable for additional validation, thereby clarifying the role of nadofaragene firadenovec in the treatment of [this patient population].”

As of February, 2025, the non-replicating adenoviral vector-based gene therapy is solely approved for those with high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumors.3

Conducting the Real-World Study

As real-world evidence on nadofaragene firadenovec is lacking, investigators from Mayo Clinic evaluated outcomes among those who received the drug at 3 of the institution’s sites from November 2023 to December 2024.2 They examined the outcomes of CR rate, DOR, high-grade recurrence-free survival (RFS), CFS, overall survival, and AEs, and defined prior intravesical chemotherapy as receipt of at least 1 induction course, not including single post-operative doses. Investigators also reported on inability to retain the drug, defined as any medication loss during installation, which included leakage around the catheter or voiding prior to the target 1-hour dwell time.

Of the 46 patients treated with nadofaragene firadenovec during the study period, 3 had not yet had follow-up cystoscopy. These 3 patients were excluded from the efficacy analysis and patient characteristic population but included in the safety analysis.

The median age of those in the real-world study was 71.0 years (IQR, 67.0-77.5) and patients had received a median of 12 (IQR, 9-15) prior BCG instillations. Most had been treated with prior intravesical chemotherapy (63%) with some having received pembrolizumab (Keytruda; 26%). The median time from NMIBC diagnosis to instillation of nadofaragene firadenovec was 33.0 months (IQR, 17.5-56.0).

Additional Efficacy Data and Safety Findings

Furthermore, the 3-, 6-, and 9-month RFS rates were examined among various patient populations and were as follows among all evaluable patients (n = 43; 79%; 66%; 51%), and those with CIS with or without high-grade Ta or T1 disease (n = 24; 83%; 74%; 60%), high-grade Ta or T1 alone disease (n = 19; 74%; 57%; 40%), prior receipt of pembrolizumab (n = 11; 73%; 53%; 20%), and prior receipt of intravesical chemotherapy (n = 27; 70%; 52%; 36%), respectively.

Regarding safety, no grade 4 or 5 AEs occurred, and grade 3 toxicities included fatigue (4%), fevers (2%), and dizziness (2%). Overall, 83% of patients experienced a grade 1 or 2 toxicity and this encompassed bladder spasm (61%), inability to retain nadofaragene firadenovec for the full target dwell time (33%), micturition urgency (20%), fatigue (13%), dysuria (13%), fevers (9%), hematuria (9%), dizziness (4%), and other AE (26%).

References

1. FDA D.I.S.C.O. Burst Edition: FDA approval of Adstiladrin (nadofaragene firadenovec-vncg) for patients with high-risk Bacillus Calmette-Guérin unresponsive non-muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors. FDA. January 20, 2023. Accessed February 26, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-disco-burst-edition-fda-approval-adstiladrin-nadofaragene-firadenovec-vncg-patients-high-risk#:~:text=On%20December%2016%2C%202022%2C%20the,with%20or%20without%20papillary%20tumors
2. Moyer J, Durant A, Nguyen M, et al. Real-world outcomes of nadofaragene firadenovec in BCG-unresponsive non-muscle invasive bladder cancer. J Clin Oncol. 2025;43(suppl 5):716. doi:10.1200/JCO.2025.43.5_suppl.716
3. Adstiladrin. Prescribing information. Ferring Pharmaceuticals; 2024. Accessed February 26, 2025. https://ferringusa.com/wp-content/uploads/sites/12/2024/10/Adstiladrin_PI.pdf