Nadofaragene firadenovec under regulatory review in Japan

Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) has accepted for review a new drug application (NDA) seeking approval of nadofaragene firadenovec-vncg (Adstiladrin) for patients with high-risk BCG-unresponsive non–muscle invasive bladder cancer (NMIBC), Ferring Pharmaceuticals announced in a news release.¹

Nadofaragene is a non-replicating gene therapy that is administered intravesically in single quarterly doses. The agent was previously approved in the US in December 2022 for patients with high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumors.²

"Nadofaragene firadenovec represents an option for those who failed NMIBC treatment,” said Professor Keiji Inoue, MD, PhD, Department of Urology, Kochi Medical School, in the news release.¹ “As the first choice after BCG failure, this bladder-sparing gene therapy offers patients a non-chemotherapy option that transforms their own bladder cells into interferon-producing factories.”

The NDA is supported by data from a phase 3 trial conducted in Japan, which achieved a 75% complete response (CR) rate at 3 months in patients with high-risk BCG-unresponsive NMIBC with CIS with or without concomitant Ta or T1 papillary lesions. Nadofaragene also demonstrated a favorable safety profile, with all treatment-related adverse events (AEs) being grade 1 (84.2%) or grade 2 (15.8%). No grade 3 or higher AEs were reported.

Inoue added, “The 75% complete response rate achieved with convenient quarterly dosing provides hope for patients who previously faced limited treatment options."

Overall, the trial is assessing the safety and efficacy of nadofaragene across 2 patient cohorts in high-risk BCG-unresponsive NMIBC: patients with CIS ± HG Ta/T1 papillary tumors, and patients with papillary tumors only. In total, 20 patients were enrolled in the first cohort through clinical trial sites across Japan. The primary end point was CR rate at 3 months.

"High-risk NMIBC patients who no longer respond to BCG have endured decades of little progress and currently face bladder removal as their primary option,” said Bipin Dalmia, Global Head, Uro-Oncology & Urology Franchise, in the news release.¹ “This PMDA acceptance validates our strategic commitment to bring this treatment to Japanese patients."

Data from the study add on to previously reported US data on the agent. In an independent US real-world study conducted at the Mayo Clinic, nadofaragene demonstrated a CR rate of 79%. The study enrolled a total of 45 patients who had BCG-unresponsive NMIBC and were treated across 3 Mayo Clinic locations in the US.

Those who achieved a CR continued with quarterly maintenance dosing. At a median follow-up of 8.2 months, 72% of patients achieved a CR or were free from high-grade recurrence at 3 months. At 6 months, CR was maintained in 62% of patients, and 100% were still alive. The cystectomy-free rate was 94%.

Further, in the phase 3 CS-003 trial (NCT02773849) that supported US approval of nadofaragene, the CR rate at 3 months was 51% (95% CI, 41 to 61) across the 157 patients enrolled in the study.² The median duration of response was 9.7 months, and 46% of responders maintained a CR for at least 1 year. At 5-year follow-up, the overall survival rate was 80%, and the cystectomy-free survival rate was 49%.

The majority of AEs in the study were grade 1 or 2, with 4% of patients experiencing a grade 3 AE.

REFERENCES

1. Ferring Japan announces PMDA acceptance of NDA filing for nadofaragene firadenovec. News release. Ferring Pharmaceuticals. September 11, 2025. Accessed September 11, 2025. https://www.businesswire.com/news/home/20250911332715/en/Ferring-Japan-announces-PMDA-Acceptance-of-NDA-Filing-for-nadofaragene-firadenovec

2. FDA approves first adenoviral vector-based gene therapy for high-risk Bacillus Calmette-Guérin unresponsive non-muscle invasive bladder cancer. News release. US Food & Drug Administration. December 16, 2022. Accessed September 11, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-first-adenoviral-vector-based-gene-therapy-high-risk-bacillus-calmette-guerin