NCCN upgrades recommendation for nadofaragene firadenovec in papillary NMIBC

An update to the 2026 National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology has elevated the recommendation for nadofaragene firadenovec-vncg (Adstiladrin) in select patients with BCG-unresponsive non–muscle invasive bladder cancer (NMIBC), Ferring Pharmaceuticals announced in a news release.¹

Specifically, the NCCN now assigns a Category 2A recommendation for nadofaragene in patients with high-risk BCG-unresponsive NMIBC with papillary tumors (+Ta/T1) without carcinoma in situ (CIS), upgrading it from a prior Category 2B designation. The agent maintains its Category 2A recommendation for patients with CIS with or without papillary disease. The NCCN Category 2A designation indicates uniform consensus among panel members that the intervention is appropriate, based on lower-level evidence.²

Nadofaragene was approved in the US in December 2022. Notably, the FDA-approved indication for nadofaragene is restricted to adult patients with CIS with or without papillary tumors. The safety and efficacy of nadofaragene in patients with papillary-only (Ta/T1) disease without CIS have not been established, underscoring that the updated NCCN recommendation extends beyond the current labeled indication.

Nadofaragene firadenovec is an intravesical, nonreplicating adenoviral vector–based gene therapy delivering the interferon alfa-2b gene to urothelial cells. It is administered once every 3 months via catheter and is designed to induce local interferon production within the bladder epithelium.

Data on nadofaragene

The FDA approval of nadofaragene was based on data from a phase 3, single-arm trial (NCT02773849) that enrolled 157 patients with high-risk BCG-unresponsive NMIBC. The study enrolled patients across 2 cohorts: 107 patients with CIS with or without Ta/T1 papillary tumors and 50 patients with Ta/T1 papillary tumors without CIS.

In the pivotal cohort of patients with CIS with or without papillary tumors, the complete response rate at 3 months was 53.4%, with 45% of responders remaining disease free at 12 months.

Long-term follow-up data published in Journal of Urology³ showed that 5.8% (95% CI, 2.2 to 12.2) of patients with CIS were high-grade recurrence-free at month 57, as well as 15% (95% CI, 6.1 to 27.8) of patients with high-grade Ta/T1. Kaplan-Meier–estimated high-grade recurrence-free survival at 57 months was 13% (95% CI 6.9-21.5) in the CIS cohort and 33% (95% CI 19.5-46.6) in the Ta/T1 cohort. Cystectomy-free survival was 49% (95% CI, 40.0 to 57.1) at month 60, comprised of 43% (95% CI, 32.2 to 53.7) in the CIS cohort and 59% (95% CI, 43.1 to 71.4) in the Ta/T1 cohort.

No new safety signals were observed with long-term follow-up. The most common drug related treatment-emergent adverse events were discharge around the catheter during instillation (25%, grade 1 or 2), fatigue (20%, grade 1 or 2), bladder spasms (16%, grade 1 or 2; 0.6%, grade 3), and micturition urgency (15%, grade 1 or 2; 1.3%, grade 3). There were no deaths attributed to the study drug.

Overall, the authors concluded, “The safety profile and convenient delivery schedule, as well as the significant number of participants were able to preserve their bladder, offers patients with this historically difficult-to-treat disease state an additional treatment option to consider.”

REFERENCES

1. Ferring announces update to NCCN guidelines expanding Category 2A recommendation for nadofaragene firadenovec-vncg (ADSTILADRIN®) in patients with BCG-unresponsive NMIBC. News release. Ferring Pharmaceuticals. March 19, 2026. Accessed March 20, 2026. https://www.businesswire.com/news/home/20260319243735/en/Ferring-Announces-Update-to-NCCN-Guidelines-Expanding-Category-2A-Recommendation-for-Nadofaragene-Firadenovec-vncg-ADSTILADRIN-in-Patients-with-BCG-Unresponsive-NMIBC

2. Development and Update of Guidelines. National Comprehensive Cancer Network. Accessed March 20, 2026. https://www.nccn.org/guidelines/guidelines-process/development-and-update-of-guidelines

3. Narayan VM, Boorjian SA, Alemozaffar M, et al. Efficacy of intravesical nadofaragene firadenovec for patients with Bacillus Calmette-Guérin-unresponsive nonmuscle-invasive bladder cancer: 5-year follow-up from a phase 3 Trial. J Urol. 2024;212(1):74-86. doi:10.1097/JU.0000000000004020