On December 16, the U.S. Food and Drug Administration (FDA) approved nadofaragene firadenovec-vncg (Adstiladrin), a nonreplicating adenoviral vector–based gene therapy indicated for the treatment of adult patients with high-risk bacillus Calmette-Guérin (BCG)-unresponsive non–muscle-invasive bladder cancer with carcinoma in situ with or without papillary tumors.
“This approval provides health-care professionals with an innovative treatment option for patients with high-risk non–muscle-invasive bladder cancer that is unresponsive to BCG therapy,” said Peter Marks, MD, PhD, Director of the FDA’s Center for Biologics Evaluation and Research.
Most newly diagnosed bladder cancers (75% to 80%) are classified as non–muscle-invasive. This type of cancer is associated with high rates of recurrence (between 30% and 80%) and the risk of progression to invasive and metastatic cancer. Treatment and care of patients with high-risk non–muscle-invasive, including those with carcinoma in situ, often involves removing the tumor and the use of BCG to reduce the risk that the cancer will recur. Few effective treatment options exist for patients who develop BCG-unresponsive disease.
New Approval
The safety and effectiveness of nadofaragene firadenovec-vncg was evaluated in a multicenter clinical study that included 157 patients with high-risk BCG-unresponsive non–muscle-invasive bladder cancer, 98 of whom had BCG-unresponsive carcinoma in situ with or without papillary tumors and could be evaluated for response. Patients received nadofaragene firadenovec-vncg once every 3 months for up to 12 months, or until unacceptable toxicity or recurrent disease.
Overall, 51% of enrolled patients receiving nadofaragene firadenovec-vncg achieved a complete response. The median duration of response was 9.7 months. About 46% of responding patients remained in complete response for at least 1 year.
The most common adverse reactions associated with nadofaragene firadenovec-vncg included bladder discharge, fatigue, bladder spasm, urinary urgency, hematuria, chills, fever, and painful urination. Individuals who are immunosuppressed or immune-deficient should not come into contact with nadofaragene firadenovec-vncg.
Nadofaragene firadenovec-vncg is administered once every 3 months into the bladder via a urinary catheter.
This application was granted Priority Review, Breakthrough Therapy, and Fast Track designations.
