Durable Efficacy of Intravesical Mitomycin Confirmed in Phase 3 Trial for NMIBC

UroGen Pharma has announced compelling 24-month duration of response (DOR) data from its pivotal phase 3 ENVISION trial (NCT05243550), reinforcing the long-term efficacy of its investigational chemoablative therapy, intravesical mitomycin (Zusduri; UGN-102), for patients with low-grade intermediate-risk non–muscle-invasive bladder cancer (LG-IR-NMIBC).1 The findings, which demonstrate a sustained response rate in patients who achieved a complete response (CR) at 3 months, position this intravesical solution as a potential first-in-class nonsurgical treatment option for this patient population.

The ENVISION trial, a single-arm, multinational, and multicenter study, evaluated the efficacy and safety of intravesical mitomycin. The primary end point was the CR rate at 3 months, and a key secondary end point was the durability of that response over time. The company's latest announcement highlights that the Kaplan-Meier estimate for a 24-month DOR was 72.2% (95% CI 64.1%–78.8%) in patients who achieved a CR. This builds upon the previously reported 79.6% CR rate at the 3-month mark. The median follow-up for this analysis was 23.7 months, and critically, the median DOR has not yet been reached, suggesting the sustained benefit could extend even further for a significant number of patients.

“For the first time, adult patients with recurrent LG-IR-NMIBC have an FDA-approved therapy. This marks a potentially transformative step forward in how we manage this chronic, highly recurrent, and disruptive cancer. [Mitomycin] is a new, outpatient treatment option for patients that can help provide a clinically meaningful recurrence-free interval, which is compelling given the highly recurrent nature of LG-IR-NMIBC,” said Sandip Prasad, MD, MPhil, Director of Genitourinary Surgical Oncology and Vice Chair of Urology at Morristown Medical Center/Atlantic Health System, NJ, and principal investigator of the ENVISION trial, in a press release.

The FDA approved intravesical mitomycin in June 2025 in this disease state.² The approval was supported by data from ENVISION.

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.3 Other 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 trial’s safety profile was consistent with previous studies of mitomycin. The most frequently reported adverse events (AEs), occurring in at least 10% of patients, were generally mild to moderate in severity. These included dysuria, increased potassium and creatinine, decreased hemoglobin, as well as other lab abnormalities and various urinary tract issues. While serious AEs were reported in 12% of patients, they were not widespread. Specific serious ARs included urinary retention (0.8%) and urethral stenosis (0.4%), which were resolvable. The overall benefit-risk profile appears favorable, supporting the therapy's potential as a viable alternative to the standard treatment of transurethral resection of bladder tumors (TURBT).

The clinical data from the ENVISION trial provides strong evidence of mitomycin's potential to alter the treatment landscape for LG-IR-NMIBC. The high complete response rate followed by a durable response at 24 months offers clinicians a promising new tool to manage a challenging disease. The ability to provide effective and long-lasting tumor control with a non-surgical approach could improve patient quality of life by reducing the need for repeated endoscopic procedures.

REFERENCES:

1. UroGen Announces 24-Month Duration of Response of 72.2% from the Pivotal Phase 3 ENVISION Trial of ZUSDURI, the First and Only FDA-Approved Medicine for Recurrent Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer. News release. UroGen Pharma. August 5, 2025. Accessed August 5, 2025. https://tinyurl.com/59pdt7bm

2. FDA approves mitomycin intravesical solution for recurrent low-grade intermediate-risk non-muscle invasive bladder cancer. News release. US FDA. June 12, 2025. Accessed August 5, 2025. https://tinyurl.com/44h6j96b

3. Prasad SM, Shishkov D, Mihaylov NV, et al. Primary chemoablation of recurrent low-grade intermediate-risk nonmuscle-invasive bladder cancer with UGN-102: a single-arm, open-label, phase 3 trial (ENVISION). J Urol. 2025;213(2):205-216. doi:10.1097/JU.0000000000004296