Review highlights efficacy, safety of mitomycin for intravesical solution in LG-IR-NMIBC

A review publication on the clinical development program for mitomycin for intravesical solution (Zusduri) supports the safety and efficacy of the agent for the treatment of patients with recurrent low-grade intermediate-risk non–muscle invasive bladder cancer (LG-IR-NMIBC).¹

Mitomycin for intravesical solution was approved by the FDA in June 2025 for this patient population. The review, published in Reviews in Urology, summarizes results from OPTIMA II (NCT03558503), ATLAS (NCT04688931), and ENVISION (NCT05243550)—the 3 late-phase clinical trials that assessed the safety and efficacy of mitomycin for intravesical solution in recurrent LG-IR-NMIBC.

"Zusduri is an FDA-approved, nonsurgical treatment that has consistently demonstrated robust, clinically significant, and durable complete responses in patients with recurrent LG-IR-NMIBC," said publication author and ENVISION principal investigator Sandip M. Prasad, MD, MPhil, director of Genitourinary Surgical Oncology and vice chair of Urology at Morristown Medical Center/Atlantic Health System in New Jersey, in a news release on the publication.² "With an acceptable safety profile manageable in routine urologic practice, Zusduri is administered in an outpatient setting without general anesthesia. This review article highlights the clinical evidence supporting Zusduri’s role as an innovative option for patients with recurrent LG-IR-NMIBC."

OPTIMA II was a phase 2b trial that included 63 patients with recurrent (77.8%) or newly diagnosed (22.2%) LG-IR-NMIBC. ATLAS was a phase 3 trial that randomly assigned 142 patients to mitomycin for intravesical solution with or without transurethral resection of bladder tumor (TURBT) (n = 142) or to TURBT alone (n = 140). The ENVISION trial supported FDA approval of mitomycin intravesical solution and is ongoing. In total, the study enrolled 240 patients.

Across the 3 clinical trials, mitomycin for intravesical solution consistently demonstrated robust, clinically significant, and durable complete response (CR) rates. Specifically, the CR rate at 3 months was 65.1% in OPTIMA II, 64.8% in ATLAS, and 79.6% in ENVISION.

The agent also showed durable disease response across all 3 trials. In ENVISION, 80.6% of patients who achieved an initial CR remained free from disease at 18 months. In OPTIMA II, the median duration of response (DOR) was 24.2 months among the 41 patients who achieved an initial CR and 42.1 months among the 17 patients who entered the long-term follow-up study.

In the ATLAS trial, which compared mitomycin for intravesical solution with TURBT, the estimated 12-month DOR after CR was 79.6% (95% CI, 69.3 to 86.8) in the mitomycin intravesical solution arm vs 69.6% (95% CI, 57.6 to 78.9) in the TURBT arm. Further, disease-free survival at 15 months was 72% (95% CI, 63.1 to 79.2) in the mitomycin for intravesical solution arm vs 49.5% (95% CI, 39.6 to 58.6) in the TURBT arm.

The safety profile for mitomycin intravesical solution was also manageable. According to its manufacturer, UroGen Pharma, “Adverse events [AEs] were primarily localized to the lower urinary tract.”

The most common AEs (≥10%), including laboratory abnormalities, were dysuria, increased potassium, increased creatinine, decreased hemoglobin, increased eosinophils, increased aspartate aminotransferase, increased alanine aminotransferase, decreased lymphocytes, urinary tract infection, decreased neutrophils, and hematuria. AEs were generally mild to moderate in severity.

Serious AEs were reported in 12% of patients, which included urinary retention (0.8%) and urethral stenosis (0.4%).

Patient-reported outcomes also showed that mitomycin for intravesical solution did not have an adverse impact on functionality, symptom burden, and quality of life in patients with LG-IR-NMIBC. Further, findings showed that most patients (90%) reported a preference for intravesical chemoablation with mitomycin for intravesical solution over TURBT.

“This comprehensive review clearly explains the body of evidence supporting Zusduri as an innovative treatment option for patients with recurrent LG-IR-NMIBC,” said Mark Schoenberg, MD, chief medical officer of UroGen, in the news release.² “By offering a nonsurgical and durable solution, Zusduri represents a major advance in the way we care for these patients.”

REFERENCES

1. Prasad SM, Schoenberg M, Louie MJ, et al. Review of UGN-102: a reverse thermal gel containing mitomycin for the treatment of recurrent, low-grade, intermediate-risk non–muscle-invasive bladder cancer. Reviews in Urology. October 5, 2025. https://reviewsinurology.com/issues/vol/24/no/3/a-reverse-thermal-gel-containing-mitomycin-for-the-treatment-of-recurrent-low-grade-intermediate-risk-non-muscle-invasive-bladder-cancer

2. ZUSDURI clinical review published in Reviews in Urology highlights durable efficacy and manageable safety profile in recurrent low-grade, intermediate-risk non–muscle invasive bladder cancer. News release. UroGen Pharma Ltd. October 2, 2025. Accessed October 2, 2025. https://www.globenewswire.com/news-release/2025/10/02/3160291/0/en/ZUSDURI-Clinical-Review-Published-in-Reviews-in-Urology-Highlights-Durable-Efficacy-and-Manageable-Safety-Profile-in-Recurrent-Low-Grade-Intermediate-Risk-Non-Muscle-Invasive-Bladd.html