UGN-103 Yields High 3-Month CR Rate in Low-Grade, Intermediate-Risk NMIBC

UGN-103 (mitomycin) for intravesical solution demonstrated a high complete response (CR) rate for the treatment of patients with recurrent low-grade, intermediate-risk non–muscle-invasive bladder cancer (NMIBC), according to preliminary data from the phase 3 UTOPIA trial (NCT06331299).1

Patients who received UGN-103 achieved a 3-month CR rate of 77.8% (95% CI, 68.3%-85.5%). Additionally, the FDA agreed that the CR and durability findings support the submission of a new drug application (NDA) for UGN-103 for recurrent low-grade, intermediate-risk NMIBC.

“The robust 77.8% 3-month CR rate observed in the UTOPIA trial is highly encouraging and reinforces the potential of UGN-103 to deliver meaningful benefits to patients,” Liz Barrett, president and chief executive officer of UroGen, stated in a news release. “In addition, the FDA’s agreement that the UTOPIA trial can support the submission of an NDA for UGN-103 represents a significant regulatory milestone and a strong validation of our clinical strategy. Together, these achievements give us significant momentum and a clear path toward potential approval, positioning UGN-103 as a key growth driver and marking an important advancement in expanding our leadership in uro-oncology. We look forward to working closely with the FDA as we complete the UTOPIA trial and prepare for an NDA submission in 2026.”

What is UGN-103?

UGN-103 is designed to offer key improvements compared with mitomycin for intravesical solution (Zusduri; UGN-102), which is the first and only FDA-approved treatment for the treatment of adult patients with low-grade, intermediate-risk NMIBC. The notable improvements include a shorter manufacturing process and a simplified reconstitution procedure without compromising prolonged drug exposure within the bladder.

In June 2025, the FDA approved UGN-102 for the treatment of adult patients with recurrent low-grade intermediate-risk NMIBC.2 The regulatory decision was supported by data from the phase 3 ENVISION trial (NCT05243550).

Findings from the single-arm study revealed that efficacy-evaluable patients who received mitomycin for intravesical solution (n = 223) experienced a 3-month CR rate of 78% (95% CI, 72%-83%). The durations of response (DOR) ranged from 0 to longer than 25 months, and 79% of responders remained in response for a minimum of 1 year.

Common any-grade adverse effects (AEs) that occurred in at least 10% of patients included increased creatinine levels, increased potassium levels, dysuria, decreased hemoglobin levels, increased aspartate aminotransferase levels, increased alanine aminotransferase levels, increased eosinophil levels, decreased lymphocyte levels, urinary tract infection, decreased neutrophil levels, and hematuria. Serious AEs were reported in 12% of patients, including urinary retention (0.8%) and urethral stenosis (0.4%). One patient experienced a fatal AE (cardiac failure).

What were the key design characteristics of UTOPIA?

UTOPIA is a single-arm, multicenter study that enrolled patients with low-grade intermediate-risk NMIBC with an anticipated life expectancy of at least the duration of the study.3 Other key inclusion criteria included a history of at least 1 prior episode of NMIBC, negative voiding cytology for high-grade disease within 8 weeks prior to screening, and adequate organ and bone marrow function. Intermediate-risk disease was defined as having 1 or 2 of the following characteristics: presence of multiple tumors; solitary tumor over 3 cm in diameter; and/or early or frequent recurrence.

Following enrollment, all patients received UGN-103 at 75 mg once weekly for 6 weeks for a total of 6 doses. The primary end point was 3-month CR rate. Secondary end points included DOR, durable CR rate, safety, mitomycin plasma concentrations, and mitomycin maximum plasma concentration.

References

1. UroGen reports 77.8% three-month complete response rate from phase 3 UTOPIA trial of UGN-103 and receives FDA agreement on NDA submission strategy in recurrent LG-IR-NMIBC based on UTOPIA trial. News release. UroGen Pharma. November 6, 2025. Accessed November 6, 2025. https://investors.urogen.com/news-releases/news-release-details/urogen-reports-778-three-month-complete-response-rate-phase-3
2. FDA approves mitomycin intravesical solution for recurrent low-grade intermediate-risk non-muscle invasive bladder cancer. FDA. June 12, 2025. Accessed November 6, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mitomycin-intravesical-solution-recurrent-low-grade-intermediate-risk-non-muscle
3. A phase 3 study of UGN-103 for treatment of patients with low-grade intermediate-risk non-muscle invasive bladder cancer (UTOPIA). ClinicalTrials.gov. Updated April 9, 2025. Accessed November 6, 2025. https://clinicaltrials.gov/study/NCT06331299