UGN-103 positioned as next step in intravesical therapy for LG-IR-NMIBC

UGN-103, a next-generation mitomycin-based intravesical therapy, is being evaluated in the phase 3 UTOPIA trial (NCT06331299) as a potential new option for patients with recurrent low-grade, intermediate-risk non–muscle invasive bladder cancer (LG-IR-NMIBC). Building on the clinical foundation of UGN-102 (Zusduri), which was approved earlier this year, UGN-103 is designed to simplify preparation and administration while maintaining comparable efficacy.

Interim data from the UTOPIA trial were reported in November 2025, showing promising early efficacy of UGN-103 in patients with LG-IR-NMIBC.¹ Specifically, at 3 months, UGN-103 achieved a complete response (CR) rate of 77.8% (95% CI, 68.3 to 85.5) in this patient population.

According to UroGen, this outcome is consistent with the 79.6% CR rate (95% CI, 73.9 to 84.5) observed in the phase 3 ENVISION trial (NCT05243550), which supported FDA approval of UGN-102. Pending additional positive data, the FDA has confirmed that results from UTOPIA may be used to support submission of a new drug application for UGN-103 in this indication.

In a recent interview with Urology Times®, Abhishek Srivastava, MD, highlighted these initial findings and shared his thoughts on the potential impact that UGN-103 might have on the treatment landscape. Notably, he emphasized that UGN-103 has the potential to streamline efficiency in the manufacturing process while providing comparable efficacy and safety to UGN-102. Down the line, this could ultimately improve access to treatment and expand options for patients with recurrent LG-IR-NMIBC, who have historically faced a treatment course characterized by repeat TURBTs.

Srivastava is a urologic oncologist at Atlantic Urology Specialists in Myrtle Beach, South Carolina.

Urology Times: UGN-103 builds on UGN-102, which was approved earlier this year. What are some of the key differentiators between these 2 agents?

Srivastava: UGN-103 is a next-gen formulation. It builds on the foundation of UGN-102, which was approved in the summer as Zusduri. UGN-103 is designed to streamline the manufacturing process, simplify reconstitution, and make it easy to use in a clinical setting, with hopefully the same effectiveness as Zusduri or UGN-102. [So, the goal is] to have the same effectiveness with possibly better efficiency.

Urology Times: UGN-103 is currently under investigation in the phase 3 UTOPIA trial. How is that trial designed? What are some of the key end points?

Srivastava: The UTOPIA trial is similar to the ENVISION trial. It is a phase 3, single-arm, multinational study in [patients with] recurrent low-grade, intermediate-risk NMIBC. The trial was designed to instill 75 mg of UGN-103 weekly for 6 doses. The primary end point of the study was to look at 3-month complete response rate, which was just recently released. The secondary end points are looking at duration of response, durable complete response, and of course, the safety profile and some pharmacokinetics based on this new formulation.

Urology Times: What have preliminary data from the trial shown so far, and how do these compare with what we saw in ENVISION?

Srivastava: The 3-month complete response rate with UGN-103 was 77.8%. These patients will be followed up until, I think, August of 2026, to get other safety [data] and the 12-month [efficacy] data. That was the initial read-out from the study released by UroGen. This is similar and in line to what was published with ENVISION study, where the 3-month complete response rate was approximately 80%. Of course, the ENVISION study has 12-month data, with an 80% durability of response, and the median duration of response was not reached with 14- to 19-month follow-up. So, it's in line with what was published with UGN-102. And the FDA has [agreed] that with this data, if it's in line with ENVISION study, it could help UroGen with a new drug application and approval subsequently for UGN-103.

Urology Times: What are some of the safety or tolerability considerations when using mitomycin-based intravesical therapy?

Srivastava: The [safety profile] is similar to any other intravesical treatment that we're used to, [with adverse events including] dysuria, hematuria, urinary tract infection, and fatigue. These are common and most likely local symptoms. There are some uncommon but serious [adverse] effects, [such as] retention and urethral strictures, which [occurred at] a very low rate in the ENVISION study. There could also be some lab shifts that could be seen like increased creatinine, potassium levels, or cytopenia that need to be carefully monitored, and which were monitored during the study.

Urology Times: Assuming continued positive data from this trial, what impact might UGN-103 have for the treatment landscape?

Srivastava: If the final data is in line with the ENVISION study with positive outcomes, I think UGN-103 has potential to further advance the treatment landscape. This new constitution will make the preparation simple and the administration of the treatment easier, while [potentially] preserving the same efficacy that was there with the ENVISION trial and Zusduri. One thing I'm not sure, and I think we'll see what the data shows or what the company eventually comes out with, but I'm hoping that this efficiency and ease in preparation can lower the cost of Zusduri. That could be something interesting we can see in the future, so I’m hopeful for that.

Urology Times: Is there anything else that you’d like to add?

Srivastava: One important point is that this is low-grade recurrent disease. There are patients who would benefit from this treatment rather than going repeated TURBTs or non-approved treatments. Bladder cancer is somewhat of a field effect, and just locally treating tumors in the bladder sometimes is not as effective as treating the entire bladder. That's where Zusduri and UGN-103 will come into play where treatment of the bladder can have good outcomes. That's what we have seen with the initial complete responses and durability of responses.

REFERENCE

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 Ltd. November 6, 2025. Accessed December 15, 2025. https://investors.urogen.com/news-releases/news-release-details/urogen-reports-778-three-month-complete-response-rate-phase-3