The Food and Drug Administration (FDA) has approved Adstiladrin (nadofaragene firadenovec-vncg) for the treatment of adults with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.
Adstiladrin is a novel nonreplicating adenoviral vector-based gene therapy that delivers a copy of a gene encoding a human interferon-alfa 2b (IFNα2b) to the bladder urothelium. The treatment, which is administered by intravesical instillation, is expected to product anti-tumor effects as a result of cell transduction and transient local expression of the IFNα2b protein.
The approval was based on data from an open-label, multicenter, single-arm phase 3 trial (ClinicalTrials.gov Identifier: NCT02773849), which evaluated the efficacy and safety of nadofaragene firadenovec-vncg in 103 adults with BCG-unresponsive, high-risk, NMIBC with CIS with or without papillary tumors following transurethral resection. Patients received nadofaragene firadenovec-vncg once every 3 months for up to 12 months (4 doses) or until unacceptable toxicity or recurrent high-grade NMIBC.
Results showed a complete response rate of 51% (95% CI, 41-61). The median duration of response was 9.7 months (range, 3 to 52+ months), and 46% of responders continued to remain free of high-grade recurrence at 12 months.
The most common adverse reactions reported were increased glucose, instillation site discharge, increased triglycerides, fatigue, bladder spasm, micturition, increased creatinine, hematuria, decreased phosphate, chills, pyrexia, and dysuria.
Adstiladrin is supplied in a carton containing 4 vials. All vials contain a nominal concentration of 3 x 1011 viral particles per mL, and each vial contains an extractable volume of no less than 20mL. The product is expected to be available in the second half of 2023.
- FDA approves first gene therapy for the treatment of high-risk, non-muscle-invasive bladder cancer. News release. US Food and Drug Administration. Accessed December 16, 2022. https://www.prnewswire.com/news-releases/fda-approves-first-gene-therapy-for-the-treatment-of-high-risk-non-muscle-invasive-bladder-cancer-301705468.html.
- Ferring receives approval from US FDA for Adstiladrin for high-risk, bcg-unresponsive non-muscle invasive bladder cancer. News release. US Food and Drug Administration. Accessed December 16, 2022. https://ferringusa.com/?press=ferring-receives-approval-from-u-s-fda-for-adstiladrin-for-high-risk-bcg-unresponsive-non-muscle-invasive-bladder-cancer.
- Adstiladrin. Package insert. Ferring; 2022. Accessed December 16, 2022. https://www.ferringusa.com/wp-content/uploads/sites/12/2022/12/ADSTILADRIN_pi.pdf.