FDA Considers UGN-102 in Low-Grade NMIBC

• The FDA has received a new drug application (NDA) seeking the approval of mitomycin for intravesical solution (UGN-102) for treating patients with low-grade, intermediate-risk, non–muscle-invasive bladder cancer (NMIBC).
• Data from the phase 3 ENVISION trial (NCT05243550) support this NDA.
• The company expects potential FDA approval of the agent in early 2025, if the NDA is accepted for filing by the FDA and priority review is granted.

An NDA seeking the approval of UGN-102 for intravesical solution has been submitted to the FDA for the potential treatment of patients with low-grade, intermediate-risk NMIBC.¹

A decision regarding potential approval from the FDA in early 2025 is expected, as long as the NDA is accepted for filing by the regulatory agency and is granted priority review.

Data from the UGN-102 clinical program, including the phase 3 ENVISION trial, support this NDA. In the ENVISION study, UGN-102 led to a 79.6% (95% CI, 73.9%-84.5%) complete response (CR) rate at 3 months after the first instillation in patients with low-grade, intermediate-risk NMIBC^.1,2 With the agent, the estimated 12-month duration of response (DOR) rate was 82.3% (95% CI, 75.9%-87.1%) in the 108 patients who had a CR at 3 months. Further, the estimated DOR rates at 15 (n = 43) and 18 months (n = 9) among those who achieved a CR at 3 months were both 80.9% (95% CI, 73.9%-86.2%).²

“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 low-grade, intermediate-risk NMIBC,” said Liz Barrett, president and chief executive officer of UroGen, in a press 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 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.”

Looking at safety, the safety profile of UGN-102 was similar in the ENVISION trial to that observed in other studies. In ENVISION, the most common treatment-emergent adverse events (TEAEs) included hematuria, dysuria, pollakiuria, urinary tract infection, urinary retention, and fatigue, and most of these were mild to moderate, resolved, or were resolving.²

Bladder cancer stages: © pikovit - stock.adobe.com

About the ENVISION Trial in NMIBC

ENVISION is a single-arm, multicenter, international trial evaluating UGN-102 in patients with low-grade, intermediate-risk NMIBC.³ Patients enrolled in the study were required to have low-grade NMIBC that was histologically confirmed by cold cup biopsy at screening or within 8 weeks before screening. A history of a previous episode of low-grade NMIBC requiring treatment with transurethral resection of bladder tumors, negative voiding cytology for high-grade disease within 8 weeks before screening, and an anticipated life expectancy of at least the trial duration were all requirements for enrollment in the study.

Patients were also required to have intermediate-risk disease, defined as having 1 or 2 of the following: the presence of multiple tumors, a solitary tumor of at least 3 cm, or early or frequent recurrence.

Once enrolled, patients were given 6 once-weekly UGN-102 instillations. The study’s primary end point is CR rate, and secondary end points consist of DOR, durable CR rate, disease-free survival, and incidence of TEAEs.

REFERENCES:

1. UroGen submits completed UGN-102 NDA seeking approval as the first FDA-approved treatment for low-grade intermendiate-risk non-muscle invasive bladder cancer. News release. UroGen Pharma Ltd. August 14, 2024. Accessed August 15, 2024. https://tinyurl.com/j59x3dpd

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. UroGen Pharma Ltd. June 13, 2024. Accessed August 15, 2024. https://tinyurl.com/bdfjj6j6

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. Updated July 12, 2024. Accessed August 15, 2024. https://clinicaltrials.gov/study/NCT05243550