Nadofaragene Firadenovec Shows Promise in Japanese Patients With BCG-Unresponsive NMIBC
The gene therapy nadofaragene firadenovec demonstrated strong clinical activity in Japanese patients with BCG-unresponsive non–muscle-invasive bladder cancer.
Bladder cancer: © SciePro - stock.adobe.com
Nadofaragene firadenovec-vncg (Adstiladrin) elicited complete responses (CRs) in three-fourths of Japanese patients with high-risk, BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC), according to initial results from a phase 3 trial shared during the 2025 Japanese Urological Association (JUA) Annual Meeting.1,2
The CR rate at 3 months was 75% (n = 15) in this patient population. Patient responders at the 3-month evaluation continued to receive nadofaragene firadenovec every 3 months until disease recurrence. Non-responders at the 3-month assessment did not receive a re-induction dose. Ferring Pharmaceuticals, the developer of the gene therapy, noted in a press release that offering re-induction is increasingly common in NMIBC trials and this approach is being explored in other trials of nadofaragene firadenovec.1
Regarding safety, drug-related adverse events (AEs) were experienced by 16 (80%) of the 20 evaluated patients. All AEs were grade 1 (64 AEs in 15 patients) or grade 2 (12 AEs in 5 patients). There were no reported grade 3, 4, or 5 AEs.
Overall, this ongoing phase 3 trial is assessing nadofaragene firadenovec in patients with BCG-unresponsive NMIBC, comprising 1 cohort of patients with carcinoma in situ (CIS) ± high-grade (HG) Ta/T1 and a second cohort of patients with papillary tumors (Ta/T1) only. The results shared at the 2025 JUA meeting were for 20 patients with CIS ± HG Ta/T1.
"When BCG therapy is ineffective, patients are forced to choose invasive surgery, ie, total bladder removal, but nadofaragene firadenovec may provide a new treatment option," first study author Keiji Inoue, MD, PhD, department of Urology, Kochi Medical School, Japan, said in the press release.1 "These findings are particularly significant for Japanese patients, as our treatment options have been more limited compared to other regions. The ability to achieve such promising results represents an important advancement for our clinical practice."
FDA Approval
The FDA approved nadofaragene firadenovec in December 2022 for the treatment of patients with high-risk, BCG-unresponsive NMIBC with CIS with or without papillary tumors.3
The approval was based on initial data from the phase 3 Study CS-003 (NCT02773849). This open-label, multicenter study included 157 patients with BCG-unresponsive NMIBC. Patients were stratified into 2 cohorts: CIS ± Ta/T1 (CIS cohort; n = 107) and high-grade Ta/T1 without CIS (papillary disease [PD] cohort; n = 50). The 5-year efficacy analysis included 103 patients from the CIS cohort and 48 patients from the PD cohort.
At a median follow-up of 50.8 months (interquartile range, 39.1-60.0), the 5-year overall survival rate 76.3% (95% CI, 64.6%-84.5%) in the CIS cohort and 85.9% (95% CI, 70.9%-93.5%) in the PD cohort. The 60-month cystectomy-free survival rates were 43.2% (95% CI, 32.2%-53.7%) and 58.7% (95% CI, 43.1%-71.4%), respectively.
"These new phase 3 findings [from the Japanese trial] affirm the safety profile of nadofaragene firadenovec, demonstrating a 3-month efficacy that is higher than previously reported in our phase 3 clinical trial [CS-003], and complements results from an ongoing independent real-world study presented earlier this year. 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,” Joern Jakobsen, MD, PhD, vice president and head of global research and medical for Uro-Oncology and Urology, Ferring, said in the press release.1
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. Posted online April 21, 2025. Accessed April 21, 2025. https://tinyurl.com/36nrk854
2. Inoue K, Kikuchi E, Nishiyama H, Nasu Y, et al. Efficacy and Safety of nadofaragene firadenovec for BCG-Unresponsive Non–Muscle-Invasive Bladder Cancer: Initial Results From an Ongoing Japanese Phase 3 Trial. Presented at the 112th Annual Meeting of the Japanese Urological Association, April 19, 2025. Available at: https://www.micenavi.jp/jua2025/search/detail_program/id:2055
3. FDA approves first adenoviral vector-based gene therapy for high-risk Bacillus Calmette-Guérin unresponsive non-muscle invasive bladder cancer. Posted online December 16, 2022. Accessed April 21, 2025. https://tinyurl.com/ye23uhrc
4. Boorjian SA, Narayan VM, Konety BR, et al. Efficacy of nadofaragene firadenovec-vncg for patients with Bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer: final results from a phase 3 trial. J Urol. Published online May 1, 2024. doi:10.1097/01.JU.0001008712.53259.7d.01
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