FDA Accepts NDA for UGN-103 in Recurrent Low-Grade Intermediate-Risk NMIBC

The FDA has accepted the new drug application (NDA) for UGN-103 (mitomycin) for intravesical solution for the treatment of adults with recurrent low-grade intermediate-risk non–muscle invasive bladder cancer (LG-IR-NMIBC), with a Prescription Drug User Fee Act (PDUFA) target action date of June 14, 2027, according to a news release from the developer UroGen Pharma. UGN-103 is an investigational next-generation formulation leveraging UroGen's proprietary RTGel® sustained-release hydrogel technology in combination with a novel lyophilized mitomycin formulation licensed from medac.

What UTOPIA trial data support the UGN-103 NDA submission?

The NDA is supported by data from the phase 3 UTOPIA trial (NCT06331299), a single-arm, multicenter study that treated 99 patients with recurrent LG-IR-NMIBC with 75 mg of UGN-103 administered intravesically once weekly for 6 weeks.²

UGN-103 produced a 3-month CR rate of 77.8% (95% CI, 68.3%–85.5%), with the Kaplan-Meier estimated probability of remaining event-free at 6 months being 94.5% among patients who achieved a CR at 3 months. The developers noted that these results are consistent with those observed in the pivotal phase 3 ENVISION trial (NCT05243550) of mitomycin (Zusduri) for intravesical solution, in which the 3-month CR rate was 79.6% (95% CI, 73.9%–84.5%).

The primary end point is complete response (CR) rate at 3 months; patients who achieve a CR at 3 months enter a follow-up phase of up to 12 months to assess duration of response (DOR).

"FDA acceptance of the UGN-103 NDA advances our vision for the next evolution of our portfolio and our continued commitment to transforming the treatment of recurrent LG-IR-NMIBC," stated Liz Barrett, president and CEO of UroGen, in the press release.¹ "Building on our experience with [mitomycin], UGN-103 combines our proprietary RTGel® technology with a novel mitomycin formulation, which leverages a streamlined manufacturing process and simplified reconstitution. We look forward to working closely with the FDA during its review and remain focused on delivering innovative treatment options for people living with this highly recurrent disease."

How does UGN-103 differ from Zusduri?

UGN-103 and Zusduri share the same active ingredient, mitomycin, and are both built on UroGen's RTGel® reverse-thermal hydrogel platform, which enables sustained drug exposure in the bladder and facilitates direct tumor ablation by non-surgical means. The key distinction is the mitomycin formulation: while Zusduri uses a liquid mitomycin solution, UGN-103 incorporates a lyophilized (freeze-dried) mitomycin formulation licensed from medac in January 2024. This change enables a more streamlined manufacturing process and simplified reconstitution designed to improve ease of use in clinical practice.

What is the unmet need in recurrent LG-IR-NMIBC?

LG-IR-NMIBC affects approximately 82,000 people in the US annually, of whom an estimated 59,000 are patients experiencing a recurrence. The disease disproportionately affects older adults, with a median age at diagnosis of 73 years. This population often carrys significant comorbidities that complicate tolerance of more intensive treatment approaches.

The standard of care for NMIBC management is transurethral resection of bladder tumor (TURBT), but up to 70% of patients with NMIBC experience at least one recurrence, and patients with LG-IR-NMIBC are particularly prone to repeated recurrences that necessitate repeated procedures. The burden of serial surgeries, each carrying anesthesia risk, procedural morbidity, and resource utilization, underscores the clinical importance of effective, non-surgical intravesical alternatives.

Mitomycin was the first and only FDA-approved treatment for adults with recurrent LG-IR-NMIBC, clearing the path for an intravesical formulation as a non-surgical ablative strategy in this setting. UGN-103, if approved, would represent an updated formulation within the same therapeutic space.

What more is in UroGen's bladder cancer pipeline?

In addition to UGN-103, the FDA cleared an investigational new drug (IND) application for UGN-501, a next-generation oncolytic virus being developed for NMIBC, in July 2026. UGN-501 is designed to selectively replicate within tumor cells to drive direct cell destruction while eliciting an anti-tumor immune response. A phase 1 study evaluating UGN-501's safety, tolerability, and feasibility was expected to begin in the fourth quarter of 2026, with early nonclinical data demonstrating cytotoxic activity across a panel of bladder cancer cell lines representing a range of tumor stages and grades.

UroGen is also evaluating UGN-104 in a phase 3 single-arm trial (NCT06774131) for the treatment of low-grade upper tract urothelial cancer (UTUC), with enrollment expected to close by the end of 2026.

References

1. UroGen announces FDA acceptance of the new drug application for UGN-103, an investigational treatment for adults with recurrent LG-IR-NMIBC. News release. UroGen Pharma Ltd. October 19, 2026. Accessed October 19, 2026. https://tinyurl.com/tk3xaup9
2. 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 September 28, 2026. Accessed October 19, 2026. https://tinyurl.com/y3azb2rd
3. 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 October 19, 2026. https://tinyurl.com/4jzzpwxm