UroGen Pharma Ltd. has announced the submission of a New Drug Application (NDA) to the FDA for UGN-102 (mitomycin) for intravesical solution, seeking approval for the treatment of patients with low-grade, intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC). The company anticipates a potential FDA decision in early 2025, contingent on the NDA's acceptance and the granting of priority review. This submission marks a significant step toward providing a non-surgical option for a challenging disease with high recurrence rates.
The NDA is supported by data from the Phase 3 ENVISION trial (NCT05243550), a single-arm, multicenter, international study. The ENVISION trial evaluated the efficacy and safety of UGN-102 in patients with LG-IR-NMIBC. Patients received six once-weekly intravesical instillations of UGN-102. The primary endpoint was the complete response (CR) rate at three months following the first instillation. Key secondary endpoints included duration of response (DOR), durable CR rate, disease-free survival, and incidence of treatment-emergent adverse events (TEAEs).
Efficacy of UGN-102
The ENVISION trial met its primary endpoint, demonstrating a 79.6% (95% CI, 73.9%-84.5%) complete response (CR) rate at three months after the first instillation. Furthermore, UGN-102 exhibited an 82.3% (95% CI, 75.9%-87.1%) 12-month duration of response (DOR) by Kaplan-Meier estimate in patients who achieved a CR at three months (n=108). The estimated DOR rates at 15 months (n=43) and 18 months (n=9) post 3-month CR were both 80.9% (95% CI, 73.9%-86.2%).
Safety Profile
The safety profile of UGN-102 in the ENVISION trial was consistent with previous studies. The most common treatment-emergent adverse events (TEAEs) included hematuria, dysuria, urinary tract infection, pollakiuria, fatigue, and urinary retention. These TEAEs were generally mild to moderate in severity and resolved or were resolving.
UGN-102: A Novel Approach
UGN-102 (mitomycin) for intravesical solution is an innovative formulation of mitomycin utilizing UroGen’s proprietary RTGel technology. This sustained-release, hydrogel-based formulation is designed to prolong the exposure of bladder tissue to mitomycin, facilitating non-surgical tumor ablation. The drug is administered via a standard urinary catheter in an outpatient setting.
The Need for New Options in NMIBC
Low-grade intermediate-risk NMIBC is characterized by high recurrence rates, often requiring repeated transurethral resection of bladder tumors (TURBT). According to UroGen, this condition affects approximately 22,000 newly diagnosed patients in the U.S. each year, with an estimated 60,000 recurrences annually. Current guideline recommendations include TURBT as the standard of care, but the high recurrence rates underscore the need for innovative therapies like UGN-102.
Management Perspective
“The completion of the NDA submission for UGN-102 marks a crucial milestone for UroGen and underscores our dedication to advancing this groundbreaking treatment for patients with LG-IR-NMIBC,” said Liz Barrett, President and CEO of UroGen. “By providing a viable alternative to repeated surgeries, if approved, UGN-102 may offer patients quality-of-life benefits and clinically meaningful recurrence-free intervals. The high recurrence rates associated with low-grade, intermediate-risk NMIBC make the need for innovative therapies like UGN-102 urgent. UGN-102 could become a valuable new option for managing this challenging disease.”
