General Information

Adstiladrin (nadofaragene firadenovec-vncg) is a non-replicating adenoviral vector-based gene therapy.

Adstiladrin is specifically indicated for the treatment of adult patients with high-risk Bacillus CalmetteGuérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

Adstiladrin is supplied as a suspension, for intravesical use. The recommended dose of Adstiladrin is 75 mL at a concentration of 3 x 1011 viral particles (vp)/mL instilled once every three (3) months into the bladder via a urinary catheter. Premedication with an anticholinergic is recommended before each instillation of Adstiladrin.

Mechanism of Action

Adstiladrin (nadofaragene firadenovec-vncg) is a non-replicating adenovirus vector-based gene therapy containing the gene interferon alfa-2b. The vector enters the cells of the bladder wall, releasing the active gene. The internal gene/DNA machinery of the cells “picks up” the gene and translates its DNA sequence, resulting in the cells secreting high quantities of interferon alfa-2b protein, a naturally occurring protein the body uses to fight cancer. This novel gene therapy approach thereby turns the patient’s own bladder wall cells into interferon microfactories, enhancing the body’s natural defenses against the cancer.

Side Effects

Adverse effects associated with the use of Adstiladrin may include, but are not limited to, the following:

•  glucose increased
• instillation site discharge
•  triglycerides increased
• fatigue
• bladder spasm
• micturition (urination urgency)
• creatinine increased
• hematuria
• phosphate decreased
• chills
• pyrexia
• dysuria

Clinical Trial Results

The FDA approval of Adstiladrin was based on results of an open-label, multicenter, single-arm trial in 103 adults with BCG-unresponsive, high-risk, non-muscle invasive bladder cancer with carcinoma in situ (CIS) with or without papillary tumors following transurethral resection, of whom 98 were considered evaluable for response. The trial met its primary endpoint with more than half (51%) of patients with carcinoma in situ with or without concomitant high-grade Ta or T1 disease (CIS ± Ta/T1) achieving a complete response (CR) by three months. Of the patients who achieved an initial CR, 46% (n=23 of 50) continued to remain free of high-grade recurrence at 12 months.