FDA accepts new drug application for UGN-102 in NMIBC

The FDA has accepted a new drug application (NDA) seeking approval of the investigational drug UGN-102 (mitomycin) for intravesical solution for the treatment of patients with low-grade, intermediate-risk non–muscle-invasive bladder cancer (LG-IR-NMIBC), UroGen Pharma announced in a news release.¹

The NDA for UGN-102 is supported by data from the phase 3 ENVISION trial.

The Prescription Drug User Fee Act (PDUFA) target action date is June 13, 2025.

"The FDA acceptance of our NDA is a pivotal moment in our journey to bring UGN-102 to patients,” said Liz Barrett, President and Chief Executive Officer of UroGen, in the news release.¹ “UGN-102 could be the first FDA-approved medicine for LG-IR-NMIBC, offering a novel approach that could expand treatment options and address unmet needs. There is an urgent need for innovative solutions in this space, and we are dedicated to collaborating with the FDA as we prepare for a potential launch of UGN-102 in 2025.”

The NDA for UGN-102 is primarily supported by findings from the phase 3 ENVISION trial (NCT05243550), which met its primary end point by demonstrating a 79.6% complete response rate in patients with LG-IR-NMIBC at 3 months following the first instillation of the therapy.

Updated data from the trial, which were reported in June 2024, showed that the 12-month duration of response (DOR) was 82.3% (95% CI, 75.9%, 87.1%) per Kaplan-Meier estimate among those patients who achieved a complete response at 3 months following the first instillation (n = 108) of UGN-102.² The study also reported a DOR of 80.9% (95% CI, 73.9%–86.2%) at both 15 (n = 43) and 18 (n = 9) months, per Kaplan-Meier estimates.

Regarding safety, the most common treatment-emergent adverse events (TEAEs) reported in the trial included dysuria, hematuria, urinary tract infection, pollakiuria, fatigue, and urinary retention. According to UroGen, TEAEs were generally mild to moderate in severity. The safety profile for UGN-102 in the ENVISION trial was consistent with previous reports.

Overall, the single-arm, multinational, multicenter, ENVISION trial is evaluating the safety and efficacy of UGN-102 as a primary chemoablative therapy in patients with LG-IR-NMIBC. In total, the study enrolled 240 adult patients across 56 sites in the US and Europe.

Patients were eligible for enrollment in the trial if they had a negative voiding cytology for high-grade disease within 8 weeks before screening, adequate organ and bone marrow function, and an anticipated life expectancy of at least the duration of the trial.³ Those included in the study received 6 once-weekly intravesical instillations of UGN-102.

The primary end point for the study was the complete response rate at 3 months following the first instillation of the therapy. Secondary outcome measures include DOR, durable complete response rate, disease-free survival, and safety outcomes, all which will be assessed for up to 63 months.

The ENVISION trial remains ongoing, with final study completion anticipated for 2028.

Additional news from UroGen

UroGen also announced earlier this month the launch of the phase 3 UTOPIA trial (NCT06331299), which will explore the safety and efficacy of UGN-103, a novel formulation of UGN-102, in patients with LG-IR-NMIBC.⁴

According to the company, UGN-103 for intravesical instillation is expected to follow the potential FDA approval and launch of UGN-102.

In total, the single-arm, multicenter UTOPIA trial plans to enroll 87 patients with LG-IR-NMIBC across clinical trial sites in the United States. Patients enrolled in the study will receive 75 mg of UGN-103 via intravesical instillation once weekly for 6 weeks.

The primary end point for the trial is the complete response rate at 3-month follow-up. Second end points include DOR, durable complete response rate, and safety, all of which may be assessed for up to 21 months.⁵

Final completion of the study is anticipated for March 2026.

References

1. UroGen announces FDA acceptance of its new drug application for UGN-102. News release. UroGen Pharma Ltd. October 15, 2024. Accessed October 16, 2024. https://investors.urogen.com/news-releases/news-release-details/urogen-announces-fda-acceptance-its-new-drug-application-ugn-102

2. UroGen announces unprecedented 82.3% duration of response at 12 months in the ENVISION trial investigating UGN-102 as potentially the first FDA-approved non-surgical treatment for LG-IR-NMIBC. News release. June 13, 2024. Accessed October 16, 2024. https://investors.urogen.com/news-releases/news-release-details/urogen-announces-unprecedented-823-duration-response-12-months

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. Last updated July 12, 2024. Accessed October 16, 2024. https://clinicaltrials.gov/study/NCT05243550

4. First patient dosed in phase 3 clinical trial of UGN-103, a next generation mitomycin-based formulation in development for the treatment of low-grade intermediate-risk non-muscle invasive bladder cancer. News release. UroGen Pharma Ltd. October 2, 2024. Accessed October 16, 2024. https://investors.urogen.com/news-releases/news-release-details/first-patient-dosed-phase-3-clinical-trial-ugn-103-next

5. A phase 3 study of UGN-103 for treatment of patients with low-grade intermediate-risk non-muscle invasive bladder cancer (UTOPIA). ClinicalTrials.gov. Last updated September 19, 2024. Accessed October 16, 2024. https://clinicaltrials.gov/study/NCT06331299