FDA Approves First Adenoviral Vector-Based Gene Therapy for High-Risk, BCG Unresponsive, Non–Muscle-Invasive Bladder Cancer

December 22, 2022

On December 16, 2022, the U.S. Food and Drug Administration approved (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-first-adenoviral-vector-based-gene-therapy-high-risk-bacillus-calmette-guerin) nadofaragene firadenovec-vncg (Adstiladrin®) for adult patients with high-risk, Bacillus Calmette-Guérin (BCG) unresponsive, carcinoma in situ (CIS), non–muscle-invasive bladder cancer (NMIBC) with or without papillary tumors.

FDA Approves First Adenoviral Vector-Based Gene Therapy for High-Risk, BCG Unresponsive, Non–Muscle-Invasive Bladder Cancer

Efficacy was evaluated in study CS-003 (NCT02773849), a multicenter, single-arm trial enrolling 157 patients with high-risk NMIBC, 98 of whom had BCG-unresponsive CIS, evaluable for response. Patients received nadofaragene firadenovec-vncg 75 ml via intravesical instillation (3 x 1,011 viral particles/ml [vp/ml]) once every three months for up to 12 months or until they developed unacceptable toxicity or recurrent high-grade NMIBC.

The major efficacy outcome measures were complete response (CR) at any time and duration of response (DoR). CR was defined as negative cystoscopy with applicable transurethral bladder tumor resection, biopsies, and urine cytology. Patients remaining in CR at 12 months were also randomized to obtain biopsies of five bladder sites. The CR rate was 51% (95% CI = 41%, 61%), the median DoR was 9.7 months (range = 3, 52+), and 46% of responding patients remained in CR for at least one year.

The most common adverse events reported in at least 10% of patients treated with nadofaragene firadenovec-vncg, including laboratory abnormalities reported in more than 15% of patients, were increased glucose, instillation site discharge, increased triglycerides, fatigue, bladder spasm, micturition urgency, increased creatinine, hematuria, decreased phosphate, chills, dysuria, and pyrexia.

The recommended nadofaragene firadenovec-vncg dose is 75 ml at a concentration of 3 x 1,011 vp/ml instilled once every three months into the bladder via a urinary catheter. Premedication with an anticholinergic is recommended prior to each instillation.

View the full prescribing information for nadofaragene firadenovec-vncg (https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/adstiladrin).

The review used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant to facilitate the FDA’s assessment.

The application was granted fast-track, breakthrough therapy, and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.

For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).

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