UGN-102 Improves Survival, Elicits CRs in Low-Grade, Intermediate-Risk NMIBC

Treatment with UGN-102 (mitomycin) with or without transurethral resection of bladder tumors (TURBT) led to an improvement in disease-free survival (DFS) compared with TURBT alone in patients with low-grade, intermediate-risk non–muscle-invasive bladder cancer (NMIBC), meeting the primary end point of the phase 3 ATLAS trial (NCT04688931). Additionally, the phase 3 ENVISION trial (NCT05243550) evaluating UGN-102 in the same patient population met its primary end point of complete response (CR) rate.¹

Data from ATLAS demonstrated that UGN-102 reduced the risk of recurrence, progression, or death by 55% compared with TURBT alone. Furthermore, the 3-month CR rate was 64.8% for patients treated with UGN-102 alone compared with 63.6% for those given TURBT alone.

Findings from ENVISION showed that 79.2% of patients experienced a CR at 3 months following initial treatment with UGN-102.

The submission of a new drug application for UGN-102 to the FDA is expected in 2024, assuming additional positive findings are read out from ENVISION.

“While TURBT is the standard treatment for bladder cancer, the recurrent nature of low-grade, intermediate-risk NMIBC means that patients will undergo multiple surgeries that come with risks for this older patient population,” Sandip Prasad, MD, MPhil, director of Genitourinary Surgical Oncology at Morristown Medical Center/Atlantic Health System in New Jersey, stated in a news release. “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.”

UGN-102 for intravesical solution is an investigational drug formulation of mitomycin. The agent features a sustained release, hydrogel-based formulation that is designed to increase the exposure of bladder tissue to mitomycin, enabling the treatment of tumors through non-surgical means.

ATLAS was a global, open-label, randomized trial that enrolled 282 patients with low-grade, intermediate-risk NMIBC in the United States, Europe, and Israel. Patients were randomly assigned 1:1 to receive UGN-102 as 6 weekly intravesical instillations, or TURBT. Patients who achieved a CR in either arm were assessed for long-term evidence of recurrence. Those in either arm with persistent disease at 3 months underwent TURBT. For patients in the control arm who did not achieve a CR, TURBT was repeated at 12 weeks (± 1 week) following initial treatment.²

The primary end point of DFS was defined differently among patients with or without a CR at 3 months. For those with a CR, DFS was the time from randomization to recurrence or death. For those without a CR, DFS was the time from first TURBT in the experimental arm or second TURBT in the control arm until recurrence or death. Secondary end points included time to recurrence, CR rate, duration of response (DOR), incidence of TURBT, health-related quality of life, and safety.

The international, single-arm, multicenter ENVISION trial evaluated UGN-102 as the primary chemoablative therapy in approximately 240 patients with low-grade, intermediate-risk NMIBC.¹

All patients received 6 weekly doses of intravesical UGN-102. Secondary end points consisted of DOR, durable CR rate, DFS, and safety.³

“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 low-grade, intermediate-risk NMIBC,” Liz Barrett, president and chief executive officer of UroGen Pharma, stated in a news release.¹ “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 [UGN-102] and now find ourselves on the precipice of a new era in bladder cancer care, and that is a very exciting place to be.”

References

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. 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
2. A phase 3 study of UGN-102 for low grade intermediate risk non-muscle-invasive bladder cancer (ATLAS). ClinicalTrials.gov. Updated April 3, 2023. Accessed July 27, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04688931
3. 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 May 9, 2023. Accessed July 27, 2023. https://clinicaltrials.gov/study/NCT05243550