Updated data from the Phase 3 ENVISION trial demonstrate a durable response with UGN-102 (mitomycin) in patients with low-grade, intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC). The trial results, announced by UroGen, show an 82.3% (95% CI, 75.9%–87.1%) duration of response (DOR) at 12 months among patients who achieved a complete response at 3 months following the first instillation of UGN-102. These findings support the potential of UGN-102 as a non-surgical alternative to the current standard of care, which often involves repeated surgeries.
ENVISION Trial Results
The ENVISION trial, a single-arm, multinational, multicenter study, evaluated the safety and efficacy of UGN-102 as a primary chemoablative therapy in patients with LG-IR-NMIBC. The study enrolled approximately 240 patients across 56 sites, each receiving six once-weekly intravesical instillations of UGN-102. The primary endpoint was the complete response rate at 3 months, with secondary outcome measures including DOR, durable complete response rate, disease-free survival (DFS), and safety outcomes.
Previously reported data showed that the ENVISION trial met its primary endpoint, with 79.6% of patients treated with UGN-102 achieving a complete response at 3 months. The updated data reveal a DOR of 80.9% (95% CI, 73.9%–86.2%) at both 15 (n = 43) and 18 (n = 9) months, according to Kaplan-Meier estimates.
Management Perspective
"UGN-102 has demonstrated a strong clinical profile across multiple trials, with these latest results of 79.6% 3-month complete response rate and 82.3% DOR at 12 months reinforcing its potential to be the first FDA-approved non-surgical option for treatment of LG-IR-NMIBC," said Liz Barrett, president and chief executive officer of UroGen. She estimates that 82,000 patients in the US suffer from this highly recurrent disease each year and may benefit from this innovative approach.
Safety Profile
The most common treatment-emergent adverse events (TEAEs) reported in the trial included dysuria, hematuria, urinary tract infection, pollakiuria, fatigue, and urinary retention. UroGen reported that TEAEs were generally mild to moderate in severity.
Regulatory Path
In January 2024, UroGen submitted a rolling New Drug Application (NDA) to the FDA for potential approval of UGN-102 for patients with LG-IR-NMIBC. With the addition of the updated ENVISION data, UroGen plans to complete the NDA in Q3 of 2024, potentially leading to an FDA decision as early as Q1 in 2025.
Supporting Commentary
"These DOR findings continue to support the development of UGN-102 as a non-surgical alternative to the current standard of care of repeated surgeries for LG-IR-NMIBC, which can impact patients’ physical health and quality of life," said Sandip Prasad, MD, MPhil, Director of Genitourinary Surgical Oncology at Morristown Medical Center/Atlantic Health System, NJ. "These results from the ENVISION study make me very optimistic about the opportunity for UGN-102, if approved, to provide another option for patients living with this highly recurrent disease."
Additional Data from ATLAS Trial
UGN-102 is also being evaluated in the Phase 3 ATLAS trial, where patients with LG-IR-NMIBC were randomly assigned to receive UGN-102 with or without transurethral resection of the bladder tumor (TURBT) or to TURBT alone.
In July 2023, it was reported that the ATLAS trial met its primary endpoint of DFS, with UGN-102 demonstrating a 55% reduction in the rate of recurrence, progression, or death vs TURBT. Additional data showed a complete response rate of 64.8% at 3 months among those who received only UGN-102, compared with 63.6% among those who received only a TURBT.
Further data from the ATLAS trial, presented at the 2024 American Urological Association Annual Meeting, assessed DFS and DOR rates among new and recurrent patients receiving UGN-102 with or without TURBT. Overall, 12-month Kaplan-Meier estimates showed a DOR of 87.5% among new patients and 69.1% among recurrent patients. Additionally, 15-month DFS estimates were 77.4% among new patients and 63.2% among recurrent patients.
