Zusduri Demonstrates Sustained Efficacy in Phase III ENVISION Trial for Recurrent Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer

UroGen has shared 24-month data from the Phase III ENVISION clinical trial (NCT05243550) of Zusduri (mitomycin) for intravesical solution, a treatment for adults with recurrent low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC).¹

FDA-approved therapy shows durable benefit

According to the data, Zusduri demonstrated a 24-month duration of response (DoR) of 72.2% by Kaplan-Meier estimate in patients who achieved a complete response (CR) at three months (79.6%). Further, the median follow-up time after a three-month CR from this readout was 23.7 months. The median DoR has not been reached.

In a press release, 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, said: "This latest update from the pivotal ENVISION trial of Zusduri showed that, among patients who achieved a complete response at three months, the probability of remaining event-free 24 months after CR was 72.2. Among patients who achieved a complete response, the event rate over time has remained stable. This DOR result highlights the sustained efficacy of the therapy and reinforces its potential as a durable treatment option. 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. Zusduri 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.”

Adverse reaction profile remains favorable

In terms of adverse reactions (ARs):

• The most common ARs (≥10%), including laboratory abnormalities, were dysuria, elevated potassium, elevated creatinine, decreased hemoglobin, elevated eosinophils, increased aspartate aminotransferase, increased alanine aminotransferase, decreased lymphocytes, urinary tract infection, decreased neutrophils, and hematuria.
• Most ARs were mild to moderate in severity.
• Serious ARs occurred in 12% of patients, with urinary retention reported in 0.8% and urethral stenosis in 0.4% of patients.

Regulatory milestone and earlier findings

Earlier in June, the FDA approved Zusduri for intravesical solution, making it the first and only FDA-approved treatment specifically indicated for adults with LG-IR-NMIBC. The approval was based on earlier data from the ENVISION study, which showed a high CR rate.²

Results from the study showed:

• Zusduri achieved a CR rate of 78% at three months, with 9% of responders remaining event-free after one year.
• Among patients who achieved a three-month CR, the 12-month DoR was 82.3%.
• DoR at both 15 and 18 months following a three-month complete response was 80.9%.
• Common adverse events (AEs) from this readout included elevated creatinine, increased potassium, dysuria, decreased hemoglobin, elevated aspartate aminotransferase, elevated alanine aminotransferase, increased eosinophils, decreased lymphocytes, urinary tract infection, decreased neutrophils, and hematuria.
• Serious AEs occurred in 12% of patients, most frequently urinary retention and urethral stenosis.

In a press release from the time of the approval, Liz Barrett, president, CEO, UroGen, said: “The approval of Zusduri represents a significant step forward for our company and for the treatment of recurrent LG-IR-NMIBC. For the first time, the estimated 59,000 US patients facing recurrent LG-IR-NMIBC each year have access to an FDA-approved medicine.”

Trial design and endpoints

ENVISION is a single-arm, multinational, multicenter pivotal study.

• The trial enrolled 240 patients across 56 clinical sites.
• Participants received six once-weekly intravesical instillations of Zusduri.
• The primary endpoint was CR rate at three months following the first instillation.
• The key secondary endpoint was the durability of response over time among patients who achieved a CR at the three-month assessment.

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. News release. August 5, 2025. Accessed August 8, 2025. https://investors.urogen.com/news-releases/news-release-details/urogen-announces-24-month-duration-response-722-pivotal-phase-3

2. FDA Approves UroGen Pharma’s Zusduri for Intravesical Solution in Recurrent Low-Grade, Intermediate-Risk Non-Muscle Invasive Bladder Cancer. Pharmaceutical Executive. June 13, 2025. Accessed August 8, 2025. https://www.pharmexec.com/view/fda-approves-urogen-pharma-zusduri-intravesical-solution-recurrent-low-grade-intermediate-risk-non-muscle-invasive-bladder-cancer