FDA Approves Mitomycin Solution in Low-Grade Intermediate-Risk NMIBC

The agency based its decision on findings from the single-arm phase 3 ENVISION trial (NCT05243550), in which investigators evaluated treatment with UGN-102 for patients with low-grade, intermediate-risk NMIBC.

The News

The FDA has approved an intravesical formulation of mitomycin (UGN-102; Zusduri) as a treatment for patients with recurrent, low-grade, intermediate-risk non–muscle-invasive bladder cancer (NMIBC), according to a press release from the agency.¹

Supporting Data

The agency based its decision on findings from the single-arm phase 3 ENVISION trial (NCT05243550), in which investigators evaluated treatment with UGN-102 for patients with low-grade, intermediate-risk NMIBC. Topline data showed a complete response (CR) rate of 78% (95% CI, 72%-83%) among 223 evaluable patients, with 79% of responders remaining in response for a minimum of 12 months.

Investigators shared additional findings from the ENVISION trial at the 2025 ASCO Genitourinary Cancer Symposium as part of different poster sessions. Findings from one poster showed that among patients with recurrent disease, the 3-month complete response (CR) rate was 79.6% (95% CI, 73.9%-84.5%), and the estimated 12-month duration of response (DOR) rate was 82.3% (95% CI, 75.9%-87.1%).²

In another poster presentation, the 3-month CR rates with UGN-102 in the ENVISION trial were 79.3% (n = 157/198) in patients with multiple tumors and 82.9% (n = 34/41) for those with a single tumor.³ Among patients with a tumor burden of more than 3 cm and 3 cm or shorter, respectively, the 3-month CR rates were 73.2% (n = 30/41) and 82.8% (n = 149/180).

According to prior findings published in The Journal of Urology, 61% (n= 146) of patients maintained a CR at 15 months after receiving UGN-102.⁴ Additionally, the estimated disease-free survival (DFS) rate at 15 months was 76% (95% CI, 69.7%-81.1%).

Expert Perspective

“These data from the ENVISION trial provide compelling evidence that treatment with UGN-102 achieves a clinically meaningful [CR] rate and also demonstrates remarkable durability in patients with [low-grade, intermediate-risk] NMIBC. The long-term results, with 82.3% [DOR] at 12 months, further strengthen UGN-102’s potential as a non-surgical, effective treatment for patients [with] the recurrent and challenging nature of [low-grade, intermediate-risk] NMIBC,” principal trial investigator Sandip M. Prasad, MD, MPhil, director of Genitourinary Surgical Oncology at Morristown Medical Center/Atlantic Health System, stated in a press release on findings from the ENVISION trial.⁵

ENVISION Trial Design

In the multicenter, single-arm, phase 3 ENVISION trial, a total of 240 patients were assigned to receive 6 once-weekly intravesical instillations of UGN-102 at 75 mg of mitomycin with sterile hydrogel.⁶

The trial’s primary end point was the CR rate at 3 months. Secondary end points included DOR, duration of CR, potentially clinically significant hematology values after baseline, and safety.

Patients 18 years and older with histologically confirmed low-grade NMIBC, a history of disease requiring treatment with transurethral resection of bladder tumors, and intermediate-risk disease were eligible for enrollment on the trial. Other eligibility criteria included having negative voiding cytology for high-grade disease within 8 weeks of screening, adequate bone marrow and organ function, and a life expectancy of at least the duration of the trial.

Safety Data

Any-grade treatment-emergent adverse effects (TEAEs) occurred in 57% of the population, with 14% experiencing grade 3 or higher TEAEs. Additionally, treatment-related TEAEs affected 34% of patients, and 2.9% had TEAEs leading to treatment discontinuation.

The most common TEAEs among patients who received UGN-102 included dysuria (23%), hematuria (8.3%), urinary tract infections (7.1%), pollakiuria (6.7%), fatigue (5.4%), urinary retention (5.0%), urethral stenosis (4.6%), and COVID-19 (3.8%). One patient each died due to pneumonia, cardiac failure, and an unknown reason; all these deaths were considered unrelated to study therapy.

The FDA accepted the new drug application for UGN-102 as a treatment for those with low-grade, intermediate-risk NMIBC in October 2024 based on findings from the ENVISION trial.⁷

In May 2025, the FDA Oncologic Drug Advisory Committee voted 5-to-4 against the benefit/risk profile of the mitomycin solution in this NMIBC population.⁸

References

1. FDA approves mitomycin intravesical solution for recurrent low-grade intermediate-risk non-muscle invasive bladder cancer. News release. FDA. June 12, 2025. Accessed June 12, 2025. https://tinyurl.com/m8xj5pbd
2. Prasad SM, Hu B, Bjurlin M, et al. Treatment of low-grade intermediate-risk non-muscle-invasive bladder cancer with UGN-102: results of the phase 3 ATLAS and ENVISION studies. J Clin Oncol. 2025;43(suppl 5):777. doi:10.1200/JCO.2025.43.5_suppl.777
3. Prasad SM, Shishkov D, Mihaylov NV, et al. Impact of tumor burden and focality in recurrent low-grade intermediate-risk non-muscle invasive bladder cancer on response to treatment with UGN-102: a subanalysis of the phase 3 ENVISION trial. J Clin Oncol. 2025;43(suppl 5):776. doi:10.1200/JCO.2025.43.5_suppl.776
4. 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
5. ENVISION trial results published in the February issue of The Journal of Urology highlight UGN-102 achievement of 82.3% duration of response at 12 months paving the way for the potential first FDA-approved treatment for LG-IR-NMIBC in June 2025. News release. UroGen. January 15, 2025. Accessed March 24, 2025. https://tinyurl.com/duvsh4w5
6. A phase 3 single-arm study of UGN-102 for treatment of low-grade intermediate-risk non-muscle invasive bladder cancer (ENVISION). ClinicalTrials.gov. Updated November 4, 2024. Accessed March 24, 2025. https://tinyurl.com/r6wpd7bu
7. UroGen announces FDA acceptance of its new drug application for UGN-102. News release. UroGen. October 15, 2024. Accessed March 24, 2025. https://tinyurl.com/2ev5mk95
8. May 20-21, 2025 meeting of the Oncologic Drugs Advisory Committee (ODAC) - day 2 FDA. Accessed June 12, 2025. https://tinyurl.com/yazxvr3y