On September 11, 2025 Ferring Pharmaceuticals Co., Ltd. reported that the PMDA has accepted the NDA for nadofaragene firadenovec for review, following submission on August 27th, 2025 (Press release, Ferring, SEP 11, 2025, View Source [SID1234655932]). This non-replicating gene therapy, administered intravesically, offers patients with NMIBC a bladder-sparing treatment option. Nadofaragene firadenovec’s quarterly dosing eliminates the burden of frequent treatments, while delivering a non-chemotherapy mechanism of action through interferon gene therapy. The NDA acceptance further highlights Ferring’s ongoing commitment to establish the new standard of care for high-risk BCG- unresponsive NMIBC.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Professor Keiji Inoue, M.D., Ph.D., Department of Urology, Kochi Medical School, stated: "Nadofaragene firadenovec represents an option for those who failed NMIBC treatment. 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 75% complete response rate achieved with convenient quarterly dosing provides hope for patients who previously faced limited treatment options."

The NDA for nadofaragene firadenovec is based on results from a Phase 3 trial conducted in Japan.1 The primary outcome of a complete response (CR) rate of 75% at 3 months, following a single dose in 20 high-risk Japanese patients with carcinoma in situ (CIS), with or without concomitant high-grade Ta or T1 papillary lesions, was presented at the 112th Annual Meeting of the Japanese Urological Association (JUA, April 17-19, 2025, Fukuoka). All treatment-related adverse events were limited to Grade 1 (84.2%) or Grade 2 (15.8%), with zero Grade 3, 4, or 5 adverse events reported – confirming the therapy’s favourable safety and tolerability profile.1

These results are consistent with independent US real-world data presented by the Mayo Clinic, which demonstrated 79% complete response rate.2 The results from the Mayo Clinic were achieved following a single quarterly dosing, representing clinical and convenience advantages over existing therapies, without requiring re-induction protocols.2 Patients who achieved complete response continued quarterly maintenance dosing.

Joern Jakobsen, M.D., Ph.D., Vice President and Head of Global Research and Medical for Uro-Oncology and Urology, Ferring Pharmaceuticals stated "Traditionally, when BCG therapy proved insufficient, patients had no choice but to undergo highly invasive treatments such as radical cystectomy or risk cancer progression. Nadofaragene firadenovec is expected to offer a new bladder-sparing treatment option. At Ferring, we are committed to addressing the unmet needs in bladder cancer treatment by providing urologists with critical insights that enable effective, personalized, and groundbreaking therapies."

"Our ambition is to establish nadofaragene firadenovec as the new standard of care and the backbone therapy for NMIBC treatment," said Bipin Dalmia, Global Head, Uro-Oncology & Urology Franchise. "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. This PMDA acceptance validates our strategic commitment to bring this treatment to Japanese patients."

About nadofaragene firadenovec
Nadofaragene firadenovec represents the first and only FDA-approved intravesical non-replicating gene therapy for adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumours.

As the first choice therapy following BCG failure, this non-chemotherapy approach utilises a non-replicating adenovirus vector-based therapy containing the interferon alfa-2b gene. Administered locally as convenient monotherapy by catheter directly into the bladder once every three months only, the mechanism transforms bladder wall cells into interferon microfactories, creating high and transient local expression of interferon alfa-2b protein – amplifying the body’s natural cancer-fighting capabilities through gene therapy rather than traditional chemotherapy approaches.

This therapeutic approach has been investigated through comprehensive clinical evaluation including 157 patients in the US with high-risk BCG-unresponsive NMIBC who demonstrated inadequate BCG response (full inclusion criteria published on clinicaltrials.gov: NCT02773849). 5-year follow-up data confirmed 80% overall survival rate and 49% cystectomy-free survival rate in adult patients with high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumours (±Ta/T1), and in patients with high-grade Ta/T1 without CIS. Long-term safety profile maintained with most treatment emergent AEs remaining transient Grade 1 or 2 (66% of all patients studied), and 4% experiencing Grade 3 AEs3.

In the real world setting, between November 2023 and October 2024, 45 patients across three Mayo Clinic locations in the US were treated with nadofaragene firadenovec for BCG-unresponsive NMIBC. Out of 45 treated patients, 29 were included in the analysis.2 After a median follow-up of 8.2 months: 72% of patients showed a complete response or were free from high-grade recurrence at 3 months. 62% maintained this response at 6 months. 94% avoided bladder removal surgery (cystectomy). 100% were still alive at 6 months.

About Non-Muscle Invasive Bladder Cancer (NMIBC)
NMIBC affects the superficial bladder layer without deeper invasion or metastatic spread. Bladder cancer represents a major clinical challenge as the 13th most commonly diagnosed cancer in Japan and ninth globally,4 with 75% presenting as NMIBC in 2022.4 While intravesical BCG remains first-line standard care for high-risk NMIBC, over 50% of patients experience disease recurrence and progression within one year, with many developing BCG-unresponsive disease requiring radical intervention.5

Current treatment options remain limited for BCG-unresponsive patients, with JUA guidelines recommending only radical cystectomy or clinical trial participation6. Nadofaragene firadenovec offers the first choice non-chemotherapy gene therapy option for these patients, providing an alternative to immediate radical surgery.