Nadofaragene Firadenovec-vncg Approved for Non–Muscle-Invasive Bladder Cancer

Bladder carcinoma micrograph.

The FDA has approved nadofaragene firadenovec-vncg (Adstiladrin®, Ferring Pharmaceuticals) for treatment of high-risk Bacillus Calmette-Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. Nadofaragene firadenovec-vncg is a non-replicating adenoviral vector-based gene therapy that cannot multiply in human cells and the first gene therapy to be approved for high-risk NMIBC.

“BCG is the most effective therapy for high-risk non–muscle-invasive bladder cancer,” wrote Stephen Boorjian, Director of the Urologic Oncology Fellowship at Mayo Clinic, and colleagues in their published results of the CS-003 study (NCT02773849), on which approval was based. “Nadofaragene firadenovec is a replication-deficient recombinant adenovirus that delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non–muscle-invasive bladder cancer.”

Safety and efficacy were measured in the phase 3, multicenter, open-label, single-arm trial in which 157 patients with high-risk BCG-unresponsive NMIBC were given a 75 mL intravesical instillation at a concentration of 3×1011 viral particles/mL of nadofaragene firadenovec-vncg once every three months for a maximum of 12 months, until disease progression, recurrence, or unacceptable toxicity. Out of the 157 patients, 98 had BCG-unresponsive CIS with or without papillary tumors and could be evaluated for response.

The key end points observed were complete response, durability of complete response, and duration of response. Significantly, 51% of the enrolled patients being treated with nadofaragene firadenovec-vncg saw a complete response; this included no trace or signs of cancer in cystoscopy, biopsied tissue, and urine. Of those who experienced a complete response, 46% remained at a complete response for at least 1 year. The median duration of response was 9.7 months.

The most common adverse events in ≥10% of patients, including laboratory abnormalities occurring in >15%, were increased glucose, instillation site discharge, increased triglycerides, fatigue, bladder spasm, micturition urgency, increased creatinine, hematuria, decreased phosphate, chills, dysuria, and pyrexia. Patients who are immunosuppressed or immunodeficient should not be treated with nadofaragene firadenovec-vncg.

“In summary, intravesical nadofaragene firadenovec for patients with BCG-unresponsive non–muscle-invasive bladder cancer showed, to our knowledge, first-of-its-kind efficacy for gene therapy, with a manageable safety profile and delivery schedule, resulting in a favorable benefit-risk profile,” concluded Dr. Boorjian and colleagues. “These data support nadofaragene firadenovec as a potentially important therapeutic advancement for a historically difficult-to-treat disease.”

The recommended dosage of nadofaragene firadenovec-vncg is 75 mL at a concentration of 3×1011 viral particles/mL instilled once every three months into the bladder via urinary catheter. Prior to each instillation, premedication with an anticholinergic is recommended.

For More Information

Boorjian SA, Alemozaffar M, Konety BR, et al (2021). Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol, 22(1):107-117. DOI:10.1016/S1470-2045(20)30540-4 (2022). Adstiladrin (=Instiladrin) in patients with high grade, Bacillus Calmette-Guerin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC). NLM identifier: NCT02773849.

Adstiladrin® (nadofaragene firadenovec-vncg) prescribing information (2022). Ferring Pharmaceuticals. Available at:

US Food and Drug Administration (2022). FDA approves first gene therapy for the treatment of high-risk, non-muscle-invasive bladder cancer. Available at:

Image credit: CoRus13. Licensed under CC0 1.0

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