FDA Approves Intravesical Mitomycin in Non–Muscle-Invasive Bladder Cancer
The FDA approved intravesical mitomycin in non–muscle-invasive bladder cancer as an nonsurgical alternative to transurethral resection of bladder tumors.
US FDA
- The FDA approved intravesical mitomycin (Zusduri, formerly UGN-102) in patients with low-grade, intermediate-risk non–muscle-invasive bladder cancer (NMIBC).
- The approval was supported by the single-arm ENVISION trial (NCT05243550).
- This is the first FDA medicine approved in this setting as a less invasive alternative to transurethral resection of bladder tumor (TURBT).
The FDA announced the approval of intravesical mitomycin (UGN-102) as a chemoablation treatment for low-grade, intermediate-risk NMIBC.1 This is the first FDA-approved medicine for low-grade, intermediate-risk NMIBC.
The approval was based on results from the phase 3 ENVISION trial, which met its primary end point of complete response rate (CR) at 3 months.2 The favorable benefit-risk profile supported the use of intravesical mitomycin as a nonsurgical alternative for transurethral resection of bladder tumors.
The current standard of care for NMIBC is TURBT, which may be required multiple times for recurrence. UGN-102 is a reverse thermal hydrogel containing mitomycin and can be given with a minimally invasive procedure given in an ambulatory setting by urinary catheter.
The multinational, single-arm, phase 3 ENVISION trial enrolled 240 patients to receive 6 weekly intravesical instillations of mitomycin. The patients had biopsy-proven recurrence of untreated low-grade, intermediate-risk NMIBC. They were evaluated at 3 months and those who had a CR consisting of negative cystoscopic examination, cytology, and for-cause biopsy received regular surveillance until disease recurrence, progression, or death.
In the study, 228 patients received all 6 planned doses and 191 (80%; 95% CI, 73.9-84.5) had a CR at 3 months and there was an 82% (95% CI, 75.9-87.1) probability of response at 12 months.2 More recent data from the trial showed an 82.8% complete response rate for those with tumor burden of 3 cm or less and 73.2% for those with tumor burden of greater than 3 cm. Additionally, patients with single or multiple tumors benefited from mitomycin.
The most common adverse events reported in the trial were dysuria, hematuria, urinary tract infection, pollakiuria, fatigue, and urinary retention.2 Serious adverse events were observed in 29 of 240 patients (12.1%) but only 2 were treatment-related, which were urinary retention and urethral stenosis, and both resolved.
In the phase 3 ATLAS study [NCT04688931], patients with low-grade intermediate-risk NMIBC were randomly assigned to TURBT or UGN-102. There was a 3-month CR rate of 64.8% with TURBT and a CR rate of 63.6% with UGN-102. Patients remained disease-free 12 months later at a rate of 79.7% in the UGN-102 arm vs 67.7% in the TURBT arm.3 The HR for duration of response favored UGN-102 [0.46 (95% CI, 0.24–0.86)].
Despite this approval, on May 21, 2025, in a narrow 5 to 4 vote, the FDA's Oncologic Drugs Advisory Committee voted that the overall benefit-risk of intravesical mitomycin is not favorable in patients with LG-IR-NMIBC.4 While acknowledging the therapy's potential and patient preference for a nonsurgical option, the committee cited unresolved concerns regarding trial design, lack of comparative data, and uncertainties around durability of response.
