The FDA approved nadofaragene firadenovec-vncg (Adstiladrin, Ferring Pharmaceuticals), the first gene therapy for 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.

Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector–based gene therapy containing the gene interferon alfa-2b, administered by catheter into the bladder once every three months. 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, the company explained. 

The approval was based in part on a phase 3, multicenter study that included 157 participants with high-risk BCG-unresponsive NMIBC, 98 of whom had BCG-unresponsive CIS with or without papillary tumors. Patients received nadofaragene firadenovec-vncg once every three months through a urinary catheter into the bladder. The treatment was given for up to 12 months, or until unacceptable toxicity or recurrent high-grade NMIBC. 

By three months, 50 of the 98 patients with carcinoma in situ with or without concomitant high-grade Ta or T1 disease achieved a complete response (no signs of cancer detected on cystoscopy, biopsied tissue and urine). Twenty-three of these patients continued to remain free of high-grade recurrence for at least one year.

The most common adverse reactions associated with the gene therapy included instillation site discharge (33%), fatigue (24%), bladder spasm (20%), micturition urgency (19%) and hematuria (17%). The discontinuation rate due to adverse reactions was 1.9%; these included bladder spasm, instillation site discharge and benign neoplasm of the bladder. Nadofaragene firadenovec-vncg should not be given to patients who are immunocompromised or immunodeficient.

The full prescribing information can be foundhere. Delaying cystectomy could lead to the development of metastatic bladder cancer, according to the prescribing information.

Bladder cancer is the sixth most common cancer in the United States, and 75% to 80% of newly diagnosed bladder cancers are NMIBC. More than half of patients who are initially treated with BCG will experience disease recurrence and progression within one year. 

“Patients with BCG-unresponsive NMIBC have historically had limited treatment options other than bladder removal surgery,” said Steven A. Boorjian, MD, the chair of the Department of Urology at Mayo Clinic in Rochester, Minn., and lead investigator on the clinical trial that led to the drug’s approval, in a statement. “The approval of Adstiladrin is therefore a significant advance in the current treatment landscape and provides a novel treatment option for patients.”

Nadofaragene firadenovec-vncg was previously rejected by the FDA in 2020 because of questions relating to the company’s manufacturing partner. Now that the treatment has received the agency’s approval,

Ferring Pharmaceuticals expects it to become commercially available in the United States in the second half of 2023.
 

—Based on press materials from the FDA and Ferring Pharmaceuticals.