FDA Bucks Advisors to Approve Mitomycin for NMIBC

The FDA has approved mitomycin intravesical solution (Zusduri, UroGen Pharma) for recurrent low-grade intermediate-risk non-muscle invasive bladder cancer.

The intravesical mitomycin formulation is meant to be an alternative to the current standard of care for recurrent disease: Transurethral resection of bladder tumor (TURBT). The surgical procedure is usually done under general anesthesia, while Zusduri can be instilled by a catheter in a urologist’s office. Treatment is once a week for 6 weeks.

The approval came shortly after the FDA’s Oncologic Drugs Advisory Committee met to consider the agency’s concern that UroGen’s approval study — ENVISION — was a single-arm trial with no direct comparison to TURBT. The agency had concerns about comparative safety because TURBT’s side effects are generally limited to the day of the procedure, while Zusduri’s side effects span the full 6 weeks of administration. There were also concerns about comparative efficacy.

One panelist commented that without a randomized trial, “it’s very hard to determine the true benefit of this, and there is toxicity.” Plus, “this is a $140,000 treatment that might not change how many follow-up TURBTs you need after 3 months.”

The panel voted 5 to 4 that the risk/benefit of Zusduri wasn’t favorable based on the available data, but in the end, the FDA apparently decided it was.

The multicenter ENVISION trial included 240 adults who had recurred after TURBT and who had multiple tumors, a solitary tumor > 3 cm, and/or a recurrence within 1 year of TURBT. Patients in the trial were treated with 75 mg once a week for 6 consecutive weeks, the approved mitomycin dosage.

Among 223 evaluable patients, 78% had a complete response, meaning no detectable disease; 12 months after a complete response, 79% of patients remained recurrence free.

As for adverse events, 10% or more patients had increased creatinine, increased potassium, dysuria, decreased hemoglobin, increased aspartate aminotransferase, increased alanine aminotransferase, increased eosinophils, decreased lymphocytes, urinary tract infection, decreased neutrophils, and hematuria.

Serious adverse events occurred in 12% of patients and included urinary retention (0.8%) and urethral stenosis (0.4%). One patient died of heart failure.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape Medical News. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected]