FDA Approves Intravesical Mitomycin for Recurrent, Low-Grade, Intermediate-Risk NMIBC

FDA

The FDA has approved mitomycin intravesical solution (Zusduri; UGN-102) for the treatment of adult patients with recurrent, low-grade, intermediate-risk, non–muscle-invasive bladder cancer (NMIBC).1

This regulatory decision is supported by findings from the phase 3 ENVISION trial (NCT05243550), in which patients received 6 once-weekly instillations of UGN-102 via standard catheter in an outpatient setting. At 3 months following the first instillation (n = 223), the complete response (CR) rate was 78% (95% CI, 72%-83%). The 12-month duration of response (DOR) rate was 79%, and DORs ranged from 0 to 25+ months.

The most common adverse effects reported in at least 10% of patients during the single-arm study included increased creatinine levels, increased potassium levels, dysuria, decreased hemoglobin levels, increased aspartate aminotransferase levels, increased alanine aminotransferase levels, increased eosinophil counts, decreased lymphocyte counts, urinary tract infection, decreased neutrophil counts, and hematuria. Serious AEs were reported in 12% of patients, which included urinary retention (0.8%) and urethral stenosis (0.4%). One patient experienced a fatal AE (cardiac failure).

Notably, in May 2025, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 5 to 4 against the risk/benefit profile of UGN-102 for the treatment of patients with recurrent, low-grade, intermediate-risk NMIBC.2 During the meeting, the FDA sought input from ODAC on whether randomized clinical trials should be required to assess treatments for this patient population, and they also voted on the risk/benefit profile of the agent in this indication.

ENVISION Trial Overview

The single-arm, multicenter, international ENVISION trial completed its target enrollment with approximately 240 patients across 56 sites. Eligible patients needed to have low-grade NMIBC histologically confirmed by cold cup biopsy at screening or within 8 weeks before screening.3

Patients needed to have a history of a previous episode of low-grade NMIBC requiring treatment with transurethral resection of bladder tumors; negative voiding cytology for high-grade disease within 8 weeks before screening; and an anticipated life expectancy of at least the trial duration. Patients also needed to have intermediate-risk disease, defined as having 1 or 2 of the following: the presence of multiple tumors; a solitary tumor of at least 3 cm; and early or frequent recurrence.

Patients were excluded if they had received BCG for urothelial carcinoma within the previous year; had a history of high-grade bladder cancer in the past 2 years; had past or current muscle-invasive bladder cancer or metastatic urothelial carcinoma; or had a history of neurogenic bladder, active urinary retention, or any other condition that would prohibit normal voiding.

Patients received 6 once-weekly UGN-102 instillations. The primary end point was CR rate at 3 months after the first instillation. A key secondary end point was durability over time in patients who had a CR at the 3-month assessment.

Per the FDA, the recommended dose of mitomycin is 75 mg instilled once per week for 6 weeks via a urinary catheter inserted into the bladder.1

Updated ENVISION Findings

Further results presented at the 2025 ASCO Annual Meeting showed that evaluable patients (n = 240) experienced a 3-month CR rate of 79.6% (95% CI, 73.9%-84.5%) and an estimated 18-month DOR rate after achieving CR at 3 months of 80.6% (95% CI, 74.0%-85.7%).4

Longer-term safety data demonstrated that treatment-emergent AEs (TEAEs) of any grade were reported in 57% of patients. The most common any-grade TEAEs comprised dysuria (23%), hematuria (8.3%), urinary tract infection (7.1%), pollakiuria (6.7%), fatigue (5.4%), and urinary retention (5.0%).

The rate of serious AEs was 12%; 2 of these AEs were deemed related to treatment.

References

1. FDA approves mitomycin intravesical solution for recurrent low-grade intermediate-risk non-muscle invasive bladder cancer. FDA. June 12, 2025. Accessed June 12, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mitomycin-intravesical-solution-recurrent-low-grade-intermediate-risk-non-muscle
2. May 21, 2025, Meeting of the Oncologic Drugs Advisory Committee (ODAC). FDA. Accessed June 12, 2025. https://www.youtube.com/live/5ecyDbK9ezc
3. UroGen announces unprecedented 82.3% duration of response at 12 months in the ENVISION trial investigating UGN-102 as potentially the first FDA-approved non-surgical treatment for LG-IR-NMIBC. News release. UroGen Pharma. June 13, 2024. Accessed April 21, 2025. https://investors.urogen.com/news-releases/news-release-details/urogen-announces-unprecedented-823-duration-response-12-months
4. Prasad SM, Mihaylov NV, Khuskivadze A, et al. Duration of response (DoR) following treatment with UGN-102 in patients with recurrent, low-grade, intermediate-risk, non-muscle invasive, bladder cancer: 18-month DoR data from the phase 3 ENVISION trial. J Clin Oncol. 2025;43(suppl 16):4598. doi:10.1200/JCO.2025.43.16_suppl.4598