Ferring Pharmaceuticals' nadofaragene firadenovec-vncg (Adstiladrin) is showing promising real-world outcomes and is being further evaluated in multiple clinical trials for non-muscle invasive bladder cancer (NMIBC). The latest data and trial updates were presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium and in recent publications.
Real-World Efficacy and Safety
Real-world data from a retrospective analysis of 46 patients with BCG-unresponsive NMIBC treated with nadofaragene firadenovec across three Mayo Clinic sites between November 2023 and December 2024, showed encouraging results. The study, presented at the ASCO Genitourinary Cancers Symposium, assessed complete response (CR) rate, duration of response (DOR), high-grade recurrence-free survival (HGRFS), cystectomy-free survival (CFS), and adverse events (AEs).
Among 24 evaluable patients with carcinoma in situ (CIS) with or without papillary disease, 79% achieved a complete response at 3 months. The median duration of response was not reached, and at a median follow-up of 7.3 months, 84% of patients maintained their CR. The Kaplan-Meier-estimated DOR was 100% at 6 months and 75% at 9 months. In patients with papillary disease, 68% were recurrence-free at 3 months, and 77% remained recurrence-free at a median follow-up of 8.9 months. CFS was 95% at a median follow-up of 8.2 months, with an overall survival (OS) of 100%.
The most common adverse events were grade 1-2 bladder spasms (61%) and failure to retain the drug for a full hour (33%). No grade 4-5 AEs were reported, and no patients discontinued treatment due to AEs.
ABLE-32 Trial for Intermediate-Risk NMIBC
The phase 3B ABLE-32 trial (NCT06510374) is currently enrolling approximately 454 patients with intermediate-risk NMIBC to receive nadofaragene firadenovec or undergo observation. This trial addresses a significant unmet need, as there are currently no FDA-approved maintenance therapies for this patient population, which experiences disease recurrence at a rate of approximately 50%.
Patients are eligible for ABLE-32 if they have newly diagnosed or recurrent intermediate-risk NMIBC, defined by the 2020 AUA/SUO guideline. Following transurethral resection of bladder tumor (TURBT), patients are randomized 1:1 to receive either nadofaragene firadenovec or observation, with crossover allowed at recurrence within 24 months. The primary endpoint is recurrence-free survival (RFS), with key secondary endpoints including RFS at 12 and 24 months, as well as safety.
Expanding Clinical Applications
Beyond the ABLE-32 trial, nadofaragene firadenovec is being investigated in several other clinical trials:
- ABLE-22 (NCT06545955): A phase 2 trial evaluating nadofaragene firadenovec as a monotherapy or in combination with chemotherapy (gemcitabine and docetaxel) or an immune checkpoint inhibitor (pembrolizumab) in patients with high-risk BCG-unresponsive NMIBC.
- LUNAR (NCT06668493): A phase 1/2 trial exploring the safety, tolerability, and efficacy of nadofaragene firadenovec instilled into the renal pelvis in patients with low-grade upper tract urothelial cancer (LG-UTUC).
- ABLE-41 (NCT06026332): An ongoing real-world evidence study assessing the early utilization, experiences, and outcomes of nadofaragene firadenovec in routine clinical care.
Mechanism of Action
Nadofaragene firadenovec is the first FDA-approved intravesical gene therapy for high-risk BCG-unresponsive NMIBC. It is a non-replicating adenovirus vector-based therapy that delivers the human IFNa2b gene to urothelial cells. Administered via catheter directly into the bladder every three months, the therapy turns bladder wall cells into interferon microfactories, enhancing the body’s natural defenses against cancer.
With ongoing trials and promising real-world data, nadofaragene firadenovec represents a significant advancement in the treatment landscape for non-muscle invasive bladder cancer.
