Phase 3 trials of UGN-102 for LG-IR-NMIBC meet primary end points

The phase 3 ATLAS and ENVISION trials exploring UGN-102 (mitomycin) for intravesical solution in patients with low-grade, intermediate-risk non–muscle-invasive bladder cancer (NMIBC) have met their primary end points, according to topline data from the trials published by UroGen, the developer of the treatment, in a news release.¹

UroGen has plans to submit a New Drug Application to the FDA following additional positive data on secondary end points from ENVISION in 2024.

UGN-102 is a hydrogel-based formulation that allows longer exposure of mitomycin to the bladder tissue. The treatment is delivered via a standard urinary catheter and has shown similar safety profiles to that in previous trials.

“UGN-102 has demonstrated a robust and consistent therapeutic profile across multiple clinical trials, providing a compelling picture of its potential to be a transformational product and advance the standard of care away from repetitive surgery to a minimally invasive, non-surgical option for LG-IR-NMIBC,” said Liz Barrett, president and Chief Executive Officer of UroGen, in the news release. “If approved, we anticipate UGN-102 to be a significant growth driver for UroGen as the first-ever non-surgical treatment option for a disease afflicting approximately 82,000 new patients in the U.S. each year. We are on track to deliver on our previously shared guidance for JELMYTO and now find ourselves on the precipice of a new era in bladder cancer care, and that is a very exciting place to be.”

UroGen has plans to submit a New Drug Application to the FDA following additional positive data on secondary end points from ENVISION in 2024.

Data from ATLAS

The phase 3 open-label, randomized controlled ATLAS trial (NCT04688931) is exploring the efficacy, durability, and safety of UGN-102 with or without a transurethral resection of bladder tumor (TURBT) compared with TURBT alone. The primary end point of the study is disease-free survival.

In total, 282 patients with LG-IR-NMIBC were enrolled in the study across sites in the United States, Europe, and Israel. Patients were randomly assigned 1:1 to receive UGN-102 or TURBT. Participants in the UGN-102 arm received 6 once-weekly instillations of UGN-102. Patients in either arm who showed presence of persistent disease at 3-month follow-up underwent a TURBT and long-term follow-up.

Initial data from the study showed that UGN-102 reduced the risk of recurrence, progression, or death by 55%. There was a complete response rate of 64.8% at 3-month follow-up among patients treated with UGN-102 alone, compared with a complete response rate of 63.6% among patients who were treated with TURBT alone.

“[Although] TURBT is the standard treatment for bladder cancer, the recurrent nature of LG-IR-NMIBC means that patients will undergo multiple surgeries that come with risks for this older patient population. Based on these compelling data, I am optimistic that UGN-102, if approved, may change the treatment paradigm for these patients who lack non-surgical options to manage the ongoing burden of this highly recurrent disease,” said Sandip Prasad, MD, MPhil, in the news release. Prasad is the director of genitourinary surgical oncology at Morristown Medical Center/Atlantic Health System in New Jersey.

Data from ENVISION

The phase 3 single-arm ENVISION trial (NCT05243550) is exploring the efficacy and safety of UGN-102 as a primary chemoablative therapy in patients with LG-IR-NMIBC. The primary end point of the study is the complete response rate at 3 months following initial treatment.

In total, the study enrolled 240 patients with LG-IR-NMIBC across 56 sites. Participants received 6 once-weekly instillations of UGN-102. At 3-month follow-up, the data showed a complete response rate of 79.2% among patients treated with UGN-102.

The study’s secondary end point will evaluate the durability of UGN-102 among patients who achieved a complete response at 3-month follow-up.

Reference

1. UGN-102 in development as the potential first non-surgical therapy for LG-IR-NMIBC, met primary endpoints in both phase 3 ATLAS and ENVISION clinical trials. News release. UroGen Pharma Ltd. July 27, 2023. Accessed July 27, 2023. https://investors.urogen.com/news-releases/news-release-details/ugn-102-development-potential-first-non-surgical-therapy-lg-ir