MECHANISM OF ACTION — Nadofaragene firadenovec is a nonreplicating adenoviral vector-based gene therapy that delivers a copy of a gene encoding interferon-alfa 2b to the bladder epithelium, where it has anti-tumor effects. Syn3, a polyamide surfactant excipient, enhances viral transduction of the urothelium.

CLINICAL STUDIES — FDA approval of nadofaragene firadenovec was based on the results of a single-arm trial in 151 patients with high-risk NMIBC, 98 of whom had BCG-unresponsive carcinoma in situ. Patients received nadofaragene firadenovec by intravesical instillation once every three months for up to 12 months unless high-grade recurrence or unacceptable toxicity occurred. A complete response was achieved in about 53% of patients within 3 months after the first dose of the drug and the response was maintained in about 46% of these patients at 12 months. The median duration of response was 9.7 months.1

ADVERSE EFFECTS — The most common adverse effects of nadofaragene firadenovec in the clinical trial were hyperglycemia, instillation-site discharge, increased triglyceride levels, fatigue, bladder spasm, micturition urgency, increased creatinine levels, hematuria, decreased phosphate levels, chills, dysuria, and pyrexia. Because nadofaragene firadenovec contains low levels of replication-competent adenovirus, it may increase the risk of disseminated adenovirus infection in immunocompromised patients.

PREGNANCY AND LACTATION — Nadofaragene firadenovec has not been studied in pregnant women. Women of reproductive potential and their male partners should use effective contraception during treatment and for 6 months (females) or 3 months (males) after the last dose. No data on the presence of the drug in human breast milk or on its effect on the breastfed infant or milk production are available.

DOSAGE, ADMINISTRATION, AND COST — Nadofaragene firadenovec is supplied in cartons containing 4 single-dose vials for intravesical instillation; each vial contains 3 x 10¹¹ viral particles (vp)/mL. The recommended dose is 75 mL instilled into the bladder and left for 1 hour once every three months. Premedication with an anticholinergic drug is recommended before each dose. The cost of Adstiladrin is not yet available.