The U.S. Food and Drug Administration (FDA) approved Adstiladrin^® (nadofaragene firadenovec-vncg) suspension on Dec. 16, 2022. It is indicated for treating adults who have high-risk, non-muscle-invasive bladder cancer (NMIBC) that has carcinoma in situ (CIS) with or without papillary tumors and that does not respond to therapy with Bacillus Calmette-Guérin (BCG). Adstiladrin is a gene therapy that uses an adenovirus vector to insert copies of a human interferon-alfa 2b (IFNα2b) gene into the cells of the bladder. It is given as 75mL of suspension at a concentration of 3 x 10¹¹ viral particles (vp)/mL instilled once every three months intravesically (directly into the bladder through a catheter). The suspension is left in place for one hour as the patient makes a quarter turn once every 15 minutes. Ferring Pharmaceuticals is aiming for a U.S. launch of Adstiladrin during the second half of 2023. It will be dispensed only through hospitals; Accredo will not have access. Its cost is not yet known. For full prescribing information, look here.

At a Glance

• Brand (Generic) Name: Adstiladrin (nadofaragene firadenovec-vncg) suspension
• Manufacturer: Ferring Pharmaceuticals
• Date Approved: Dec. 16, 2022
• Indication: for the treatment of adult patients who have high-risk BCG-unresponsive NMIBC with carcinoma in situ with or without papillary tumors.
• Dosage Forms Available: intravesical suspension at a concentration of3 x 10¹¹ vp/mL, shipped frozen in packages containing four vials of suspension
• Launch Date: Second half of 2023
• Estimated Annual Cost: Not yet known
• Bladder cancer is diagnosed for more than 80,000 Americans, annually, with men three times as likely as women to have it. About three-quarters of cases are non-invasive, which means cancer cells have not penetrated into the muscles beyond the inner lining of the bladder.
• The five-year survival rate for CIS of the bladder is high at 96%, dropping to 70% if cancer has spread to other parts of the bladder and to 38% if lymph nodes and other body parts outside of the bladder are involved.
• Initial treatment for NMIBC usually involves surgical removal of tumors and treatment with intravesical chemotherapy (chemo) or a vaccine, BCG.
• As many as one-half of NMIBC tumors will return within around one year after treatment, however; and eventually, 30% to 40% of cases no longer respond to BCG.
• Current options for BCG-resistant NMIBC at high risk of recurrence and progression to invasive cancer include removal of the bladder (cystectomy) and surrounding tissues or Keytruda^® (pembrolizumab – Merck) at a recommended dose of 200mg administered in 30-minute long intravenous (IV) infusions once every three weeks for up to 24 months.
• Adstiladrin consists of an adenovirus vector that contains IFNα2b genes. The viral cells, which cannot divide, disintegrate after they infiltrate cells in the bladder walls. The IFNα2b genes that are released prompt the cells to produce large amounts of IFNα2b, which greatly increases the body’s immune response against the cancer cells.
• In the phase III clinical trial that involved 98 patients, about 51% had a complete response (CR) to Adstiladrin three months after the first treatment. NMIBC did not return within 12 months for nearly one-half (46%) of the responders.
• Most side effects from treatment were mild, with fatigue and fever among the most common systemic effects and bladder discharge, bladder spasms or bloody urine among the most common localized effects.
• Adstiladrin was approved with the FDA’s Breakthrough Therapy, Fast Track, and Priority Review designations.