NDA submitted to FDA for UGN-102 in low-grade intermediate-risk NMIBC

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

An FDA decision on the NDA for UGN-102 is anticipated for the first quarter of 2025.

The NDA rolling submission process for UGN-102 was first initiated in March 2024. The company previously reported that they were ahead of schedule for NDA filing, with the completed NDA submission first anticipated for September 2024.²

Pending that the FDA accepts the filing and grants priority review to UGN-102, a decision on the NDA is anticipated for the first quarter of 2025. If approved, UGN-102 has the potential to become the first FDA-approved treatment for patients with LG-IR-NMIBC, according to UroGen.

“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, in the news release.¹ “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 LG-IR-NMIBC make the need for innovative therapies like UGN-102 urgent. UGN-102 could become a valuable new option for managing this challenging disease.”

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 was recently 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-102.³ 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 has enrolled approximately 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.⁴ 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. 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.

References

1. UroGen submits completed UGN-102 NDA seeking approval as the first FDA-approved treatment for low-grade intermediate-risk non-muscle invasive bladder cancer. News release. UroGen Pharma Ltd. Published online and accessed August 14, 2024. https://investors.urogen.com/news-releases/news-release-details/urogen-submits-completed-ugn-102-nda-seeking-approval-first-fda

2. UroGen Pharma Ahead of Schedule to Complete UGN-102 NDA Submission and Reports 2024 Second Quarter Financial Results and Business Highlights. News release. UroGen Pharma Ltd. August 13, 2024. Accessed August 14, 2024. https://investors.urogen.com/news-releases/news-release-details/urogen-pharma-ahead-schedule-complete-ugn-102-nda-submission-and

3. 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 August 14, 2024. https://investors.urogen.com/news-releases/news-release-details/urogen-announces-unprecedented-823-duration-response-12-months

4. 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 August 14, 2024. https://clinicaltrials.gov/study/NCT05243550