Japanese patients with high-risk BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) showed a 75% complete response rate to nadofaragene firadenovec therapy, according to new Phase 3 trial data presented at the 112th Annual Meeting of the Japanese Urological Association in Fukuoka.
The open-label study, conducted across 25 centers in Japan, evaluated the gene therapy in patients with carcinoma in situ (CIS) with or without papillary tumors. Among the 20 patients assessed at the three-month mark, 15 achieved a complete response following a single quarterly administration.
"When BCG therapy is ineffective, patients are forced to choose invasive surgery, i.e., total bladder removal, but nadofaragene firadenovec may provide a new treatment option," explained Professor Keiji Inoue, MD, PhD, from the Department of Urology at Kochi Medical School. "These findings are particularly significant for Japanese patients, as our treatment options have been more limited compared to other regions."
Treatment Safety Profile
The safety data revealed a manageable profile with 80% of participants (16 patients) experiencing treatment-related adverse events (AEs). Of the 76 total AEs recorded, 84.2% were Grade 1 and 15.8% were Grade 2. Notably, no Grade 3, 4, or 5 adverse events were reported, suggesting a well-tolerated therapy.
This safety profile aligns with previous studies while the efficacy appears higher than reported in the US Phase 3 trial that led to FDA approval in December 2022. The US trial showed a 51% complete response rate at any time point, with 46% of responders maintaining their response for at least one year.
Clinical Significance
Bladder cancer represents the ninth most common cancer worldwide, with approximately 614,000 new cases diagnosed annually. Non-muscle invasive bladder cancer accounts for about 75% of newly diagnosed cases. For patients who don't respond to standard BCG treatment, options have been severely limited, often leading to radical cystectomy (complete bladder removal).
"These initial phase 3 findings from Japan affirm the safety profile of Adstiladrin, demonstrating a 3-month efficacy that appears to be higher than previously reported in our phase 3 clinical trial, and consistent with results from an ongoing independent real-world study presented earlier this year," said Joern Jakobsen, MD, PhD, Vice President and Head of Global Research and Medical for Uro-Oncology and Urology at Ferring Pharmaceuticals.
The real-world data referenced by Dr. Jakobsen was presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium, showing a 79% complete response rate among patients treated with nadofaragene across Mayo Clinic locations.
Mechanism of Action
Nadofaragene firadenovec (marketed as ADSTILADRIN® in the US) represents a novel approach to treating bladder cancer. It is a non-replicating adenovirus vector-based therapy containing the gene interferon alfa-2b, administered directly into the bladder by catheter once every three months.
The therapy works by entering the cells of the bladder wall, releasing the active gene and causing the bladder's cells to secrete high levels of interferon alfa-2b protein, a naturally occurring protein the body uses to fight cancer. This approach essentially transforms the bladder wall cells into "interferon microfactories," enhancing the body's natural defenses against cancer.
Study Design and Future Directions
The ongoing Phase 3 Japanese trial (NCT05704244) is evaluating nadofaragene firadenovec in two cohorts: patients with CIS with or without high-grade Ta/T1 disease, and patients with papillary tumors only. The trial plans to enroll a total of 25 patients, with final study completion anticipated for September 2029.
Patients who responded at the three-month assessment received continued quarterly doses until disease recurrence. Unlike some other NMIBC trials, this conservatively designed protocol did not offer re-induction doses to non-responders at three months, though this approach is being explored in other trials with nadofaragene firadenovec.
Regulatory Status
While nadofaragene firadenovec received FDA approval in the United States in December 2022 for adult patients with high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumors, the therapy has not yet been approved in Japan. These promising results from the Japanese trial may support future regulatory submissions in the region.
Long-term data from the US trial showed an overall survival rate of 80% and a cystectomy-free survival rate of 49% at 60 months, highlighting the potential durability of response with this therapy.
For Japanese patients facing limited treatment options after BCG failure, nadofaragene firadenovec represents a potentially significant advancement that could delay or prevent the need for radical cystectomy, preserving quality of life while effectively managing this challenging disease.
