Nadofaragene Firadenovec Yields High 3-Month CR Rates in High-Risk BCG-Unresponsive NMIBC With CIS

Non–Muscle Invasive Bladder Cancer | Image
Credit: © Sebastian Kaulitzki – stock.adobe.com

Treatment with nadofaragene firadenovec-vncg (Adstiladrin) produced a high 3-month complete response (CR) rate of 75% in patients with high-risk, BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors (±Ta/T1; n = 20), according to initial results from an ongoing phase 3 trial (NCT05704244) in Japan.1

In this study, the safety and efficacy of nadofaragene firadenovec are being evaluated in 2 cohorts comprising those with CIS (with or without high‑grade Ta/T1 disease) and those with papillary tumors only. Additional safety data from the CIS cohort, which were presented at the 112th Annual Meeting of the Japanese Urological Association, showed that 80% of patients experienced treatment‑related adverse effects, all of which were grade 1 (84.2%) or grade 2 (15.8%). Notably, these efficacy and safety results followed just a single quarterly administration.

Ferring Pharmaceuticals, the drug’s developer, plans to present the full dataset at an upcoming congress.

“When BCG therapy is ineffective, patients are forced to choose invasive surgery, [such as] total bladder removal, but nadofaragene firadenovec may provide a new treatment option,” Keiji Inoue, MD, PhD, Department of Urology at Kochi Medical School, stated in a news release. “These findings are particularly significant for Japanese patients, as our treatment options have been more limited compared with other regions. The ability to achieve such promising results represents an important advancement for our clinical practice.”

Overview of the Phase 3 Japanese Study

The open-label, phase 3 Japanese study plans to enroll 25 patients with high-risk BCG-unresponsive NMIBC with CIS only, Ta/T1 high-grade disease with concomitant CIS, or Ta/T1 high-grade disease without concomitant CIS.2 This included patients who did not respond to BCG treatment and experienced persistent high-grade recurrence within 12 months after initiation of BCG; those with CIS who relapsed within 12 months of their last intravesical treatment despite achieving an initial CR; and those with high-grade Ta/T1 NMIBC who relapsed within 6 months of their last intravesical treatment.

Additional eligibility criteria include life expectancy greater than 2 years, an ECOG performance score of 2 or less, and prostate cancer on active surveillance at low risk for progression, defined as prostate-specific antigen (PSA) expression of less than 10 ng/dL.

Upon enrollment, patients will receive 75 ml of intravesical nadofaragene firadenovec once every 3 months via a urinary catheter without reinduction. Notably, patients who responded at the 3-month assessment will continue this dosing schedule until disease recurrence.1

The primary end point is CR rate at any time following the first dose.2 Secondary end points include DOR, duration of event-free survival, time to cystectomy, OS, and safety.

Previously Reported Data With Nadofaragene Firadenovec

Nadofaragene firadenovec is the first and only intravesical non-replicating gene therapy to be FDA approved for adult patients with high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumors.3

This regulatory decision was supported by data from the phase 3 CS‑003 trial (NCT02773849), which showed a 51% CR rate (95% CI, 41%-61%) with nadofaragene firadenovec. Of these responders, 46% maintained a CR for at least 1 year, with a median duration of response (DOR) of 9.7 months.

The efficacy and safety data from the Japanese study are consistent with findings from a real-world study in the United States, which were presented at the 2025 Genitourinary Cancers Symposium.4 At the 3-month assessment, 79% of evaluable patients with NMIBC and CIS (n = 24) achieved a CR. At a median follow-up of 7.3 months, 84% of responders maintained their CRs. The median DOR was not reached. Moreover, at a median follow-up of 8.2 months, patients who received the intravesical therapy (n = 43) achieved a cystectomy-free survival rate of 95% and an OS rate of 100%.

"Initial phase 3 findings [from Japan] affirm the safety profile of nadofaragene firadenovec, 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,” Joern Jakobsen, MD, PhD, vice president and head of global research and medical for uro-oncology and urology at Ferring Pharmaceuticals, concluded in the news release.1 “Collectively, the data are broadening our understanding of the value that nadofaragene firadenovec offers, furthering our journey to establish nadofaragene firadenovec as the new standard of care and backbone therapy across the urothelial cancer disease spectrum.”

References

1. Ferring announces initial data from phase 3 trial in Japanese patients demonstrating 75% complete response rate at 3 months with (nadofaragene firadenovec) in BCG-unresponsive NMIBC patients. News release. Ferring Pharmaceuticals. April 21, 2025. Accessed April 22, 2025. https://www.businesswire.com/news/home/20250421675994/en/Ferring-Announces-Initial-Data-from-Phase-3-Trial-in-Japanese-Patients-Demonstrating-75-Complete-Response-Rate-at-3-Months-with-nadofaragene-firadenovec-in-BCG-unresponsive-NMIBC-Patients1
2. Safety and efficacy of FE 999326 administered intravesically to Japanese subjects with high-grade, BCG unresponsive, non-muscle invasive bladder cancer (NMIBC). ClinicalTrials.gov. Last updated February 13, 2025. Accessed April 22, 2025. https://clinicaltrials.gov/study/NCT05704244
3. FDA approves first adenoviral vector-based gene therapy for high-risk Bacillus Celmette-Guérin unresponsive non-muscle invasive bladder cancer. FDA. Updated December 19, 2022. Accessed April 22, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-first-adenoviral-vector-based-gene-therapy-high-risk-bacillus-calmette-guerin
4. 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