UroGen Pharma's UGN-102 (mitomycin) has shown promising results as a potential non-surgical treatment option for patients with low-grade, intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC). The drug met its primary endpoints in both the Phase 3 ATLAS and ENVISION trials, offering hope for a less invasive approach to managing this recurrent disease.
Phase 3 Trial Results
The ATLAS trial (NCT04688931), a randomized, controlled study, evaluated UGN-102 with or without transurethral resection of bladder tumor (TURBT) against TURBT alone. The results indicated that UGN-102 reduced the risk of recurrence, progression, or death by 55% compared to TURBT alone (p<0.05). The complete response (CR) rate at 3 months was 64.8% in the UGN-102 arm versus 63.6% in the TURBT arm.
The ENVISION trial (NCT05243550), a single-arm study, assessed UGN-102 as a primary chemoablative therapy. The trial achieved its primary endpoint with a 79.2% CR rate at 3 months among patients treated with UGN-102.
UGN-102: A Novel Approach
UGN-102 is a sustained-release, hydrogel-based formulation of mitomycin designed to prolong exposure of bladder tissue to the drug. Administered via a standard urinary catheter in an outpatient setting, it offers a potential alternative to repetitive surgical interventions.
Expert Commentary
"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," said Dr. Sandip Prasad, director of Genitourinary Surgical Oncology at Morristown Medical Center/Atlantic Health System. "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."
Trial Designs and Endpoints
The ATLAS trial enrolled 282 patients across sites in the United States, Europe, and Israel. Patients were randomized to receive either UGN-102 or TURBT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included time to recurrence, CR rate, and duration of response (DOR).
The ENVISION trial included 240 patients across 56 sites. All patients received six weekly intravesical doses of UGN-102. The primary endpoint was the CR rate at 3 months. Secondary endpoints included DOR, durable CR rate, and DFS.
Future Directions
UroGen Pharma anticipates submitting a New Drug Application (NDA) to the FDA in 2024, assuming further positive findings from the ENVISION trial, particularly regarding the duration of response. If approved, UGN-102 could become the first non-surgical treatment option for LG-IR-NMIBC, potentially transforming the standard of care.
"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 Pharma.
