
A novel gene therapy designed to treat unresponsive nonmuscle invasive bladder cancer (NMIBC) is making its way into clinics.
Following an announcement by the U.S. Department of Veterans Affairs (VA) in January, UC San Diego Health this week began offering gene therapy nadofaragene firadenovec (Adstiladrin) to people with localized bladder cancer. UC San Diego Health urologists have initiated bladder gene treatments on five patients.
The gene therapy, which is delivered via a urinary catheter, holds promise in delaying or eliminating the necessity for bladder removal, Dr. Amirali Salmasi said in a UC San Diego Health news release. Salmasi is an associate professor of urology at the University of California (UC), San Diego School of Medicine; a urologist at UC San Diego Health; and a UC San Diego Moores Cancer Center member.
"The primary treatment for NMIBC in the past typically involved surgical resection, followed by therapies into the bladder, like immunotherapy or chemotherapy," Salmasi explained. "Unfortunately, if these interventions proved ineffective, the standard course of action involved bladder removal, which poses a substantial morbidity risk."
Adstiladrin was approved by the U.S. Food and Drug Administration (FDA) under the Biologics License Application pathway on December 16, 2022. The gene therapy is a nonreplicating recombinant adenovirus that when administered enters the cells of the bladder wall. It works by releasing the human interferon alfa-2b (IFNα2b) gene and causing the bladder's cell walls to secrete high quantities of IFNα2b protein, a naturally occurring protein that the body uses to fight cancer.
"This approach essentially turns the bladder wall cells into interferon microfactories, enhancing the body's own natural defenses against the cancer," Ferring Pharmaceuticals, the developer and manufacturer of Adstiladrin, said in a January 2023 news release.
Researchers evaluated the safety and effectiveness of Adstiladrin in a multicenter single-arm trial comprising 157 patients with high-risk NMIBC, 98 of whom had Bacillus Calmette-Guérin-unresponsive carcinoma in situ evaluable for response. The major efficacy outcome measures were complete response at any time and duration of response.
A complete response was defined as negative cystoscopy with applicable transurethral resection of the bladder tumor and biopsies and urine cytology. Random bladder biopsies of five sites were conducted in patients remaining in complete response at 12 months. The complete response rate was 51%, the median duration of response was 9.7 months, and 46% of responding patients remained in complete response for at least one year, according to the FDA.
Adstiladrin includes warnings, such as delaying cystectomy could lead to the development of metastatic bladder cancer, which can be lethal, and a risk of disseminated adenovirus infection, especially for patients and healthcare professionals who are immunocompromised or immunodeficient, according to the FDA.