Nadofaragene Firadenovec Demonstrates Durable 5-Year Activity in NMIBC

The gene therapy nadofaragene firadenovec-vncg (Adstiladrin) led to durable antitumor activity in a subset of patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) either with carcinoma in situ (CIS) or papillary disease as well as bladder preservation in approximately half of the overall population, according to 5-year data from the phase 3 Study CS-003 (NCT02773849) presented at the 2024 American Urological Association Annual Meeting.¹

The open-label, multicenter study included 157 patients enrolled in 2 cohorts: patients with CIS ± Ta/T1 (CIS cohort; n = 107) and patients with 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) for all treated patients, the 5-year overall survival rates were 76.3% (95% CI, 64.6-84.5) and 85.9% (95% CI, 70.9-93.5) in the CIS and PD cohorts, respectively. At 60 months, the cystectomy-free survival rate was 43.2% (95% CI, 32.2-53.7) in the CIS cohort and 58.7% (95% CI, 43.1-71.4) in the PD cohort.

In the CIS cohort, among patients who had a complete response at 3 months (n = 55), 10.9% (n = 6) remained high-grade recurrence-free (HGRF) at 57 months. In the PD cohort, of the 35 patients who were HGRF at the 3 months, 20% (n= 7) remained HGRF at 57 months.

Based on previously reported findings from this study, the FDA approved nadofaragene firadenovec in December 2022 for use in this setting.²

“At 60 months, nadofaragene allowed bladder preservation in nearly half of the patients in the CIS cohort and two-thirds of patients in the Ta/T1 (PD) cohort,” Vikram Narayan, MD, said when presenting the findings at the AUA meeting. “Nadofaragene represents a novel treatment option for BCG-unresponsive NMIBC, particularly for patients who are unwilling or unable to undergo cystectomy, with a convenient dosing pattern for patients (once every 3 months),” added Narayan, who is director of Urological Oncology at Grady Memorial Hospital and an assistant professor in the Department of Urology at Emory University School of Medicine at Winship Cancer Institute.

The overall study population was heavily pretreated, with a median of 12 prior BCG doses. Patients were treated with 75 mL of nadofaragene firadenovec (3 × 10¹¹ viral particles/mL) once every 3 months for a maximum of 4 doses. The study protocol stipulated that patients receive 5-site biopsy at 12 months and patients who had no evidence of high-grade recurrence were eligible to continue receiving nadofaragene firadenovec every 3 months.

Regarding safety, nadofaragene was well tolerated and most treatment-emergent adverse events (TEAEs) were grade 1/2 and resolved quickly. Overall, 66.2% of patients had a grade 1/2 TEAE and 3.8% had a grade 3 TEAE. Grade 3 TEAEs included 2 cases of micturition urgency and 1 case each of bladder spasm, syncope, hypertension, and urinary incontinence. At the 5-year follow-up, there were no new safety signals reported, along with no grade 4 TEAEs or treatment-related deaths.

Ferring Pharmaceuticals, the developer of nadofaragene, announced in January 2024 that nadofaragene firadenovec is now fully available in the United States for eligible patients.³

References

1. 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
2. FDA approves first gene therapy for the treatment of high-risk, non-muscle-invasive bladder cancer. News release. FDA. December 16, 2022. Accessed January 16, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treatment-high-risk-non-muscle-invasive-bladder-cancer
3. Ferring announces full availability of ADSTILADRIN (nadofaragene firadenovec-vncg) in the U.S. News release. Ferring Pharmaceuticals. Published online and accessed January 16, 2024. https://www.businesswire.com/news/home/20240116546395/en/Ferring-Announces-Full-Availability-of-ADSTILADRIN%C2%AE-nadofaragene-firadenovec-vncg-in-the-U.S.