UGN-102 data published in Journal of Urology as FDA weighs NMIBC approval

Author(s):

Key Takeaways

UGN-102 showed a 79.6% complete response rate at 3 months in the ENVISION trial for LG-IR-NMIBC.
The 12-month duration of response was 82.3%, with disease-free survival at 15 months reaching 76%.
The FDA accepted the NDA for UGN-102, potentially making it the first non-surgical treatment for LG-IR-NMIBC.
The safety profile was consistent, with most adverse events being mild to moderate, and serious AEs in 12.1% of patients.
The ongoing ENVISION trial enrolled 240 patients, with final completion anticipated in 2028.

The phase 3 ENVISION trial met its primary end point by demonstrating a 79.6% complete response rate at 3 months following the first instillation of the therapy.

Data from the phase 3 ENVISION trial (NCT05243550) supporting a potential FDA approval of UGN-102 (mitomycin) for intravesical solution in patients with low-grade, intermediate-risk non–muscle-invasive bladder cancer (LG-IR-NMIBC) have been published in the Journal of Urology.^1,2

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

“These data demonstrate that treatment with UGN-102 results in a clinically meaningful [complete response] rate and that the durability of the response in patients with LG-IR-NMIBC is robust,” said principal investigator Sandip Prasad, MD, MPhil, director of genitourinary surgical oncology at Morristown Medical Center/Atlantic Health System in New Jersey, in a news release on the published data.2 “This study adds to the mounting evidence supporting UGN-102 as a potentially valuable treatment option for patients with recurrent LG-IR-NMIBC.”

A new drug application (NDA) for UGN-102 was submitted to the FDA in August 2024, seeking approval of the therapy for patients with LG-IR-NMIBC. The FDA accepted the NDA in October 2024, issuing a target action date of June 13, 2025.³ According to UroGen Pharma, the developer of the therapy, UGN-102 has the potential to become the first chemoablative, non-surgical treatment option for patients with LG-IR-NMIBC if approved.

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

Updated data from the trial, which were first reported in June 2024, showed that the 12-month duration of response (DOR) was 82.3% (95% CI, 75.9% to 87.1%) per Kaplan-Meier estimate among those patients who achieved a complete response at 3 months following the first instillation of UGN-102 (n = 108).

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. At a median follow-up of 13.9 months, the median DOR was not estimable.

At 15 months, 61% of patients (n = 146; 95% CI, 54 to 67) maintained a complete response following treatment. Disease-free survival at 15 months was 76% (95% CI: 69.7, 81.1) per Kaplan-Meier estimate.

The safety profile for UGN-102 in the ENVISION trial was consistent with previous reports.

The most common treatment-emergent adverse events (TEAEs) reported in the trial included dysuria (22%), hematuria (8.3%), urinary tract infection (7.1%), pollakiuria (6.7%), fatigue (5.4%), and urinary retention (5.0%). According to the authors, TEAEs were generally mild to moderate in severity. Serious AEs occurred in 12.1% of patients, with only 2 being related to treatment (urinary retention/urethral stenosis). Both treatment-related AEs were resolved.

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 United States 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. Among all patients included in the trial, 95% (228) received all 6 planned doses 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.

References

1. Prasad SM, Shishkov D, Mihaylov NV, et al. Primary chemoablation of recurrent low-grade intermediate-risk nonmuscle-invasive bladder cancer with UGN-102: A single-arm, open-label, phase 3 trial (ENVISION). J Urol. 2024 Oct 24:101097JU0000000000004296. doi:10.1097/JU.0000000000004296

2. ENVISION trial results published in the Journal of Urology report 82.3% duration of response 12 months after achieving complete response for UGN-102, potentially first FDA-approved non-surgical treatment for LG-IR-NMIBC. News release. UroGen Pharma Ltd. Published online and accessed October 28, 2024. https://investors.urogen.com/news-releases/news-release-details/envision-trial-results-published-journal-urology-report-823

3.UroGen announces FDA acceptance of its new drug application for UGN-102. News release. UroGen Pharma Ltd. October 15, 2024. Accessed October 28, 2024. https://investors.urogen.com/news-releases/news-release-details/urogen-announces-fda-acceptance-its-new-drug-application-ugn-102

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 October 28, 2024. https://clinicaltrials.gov/study/NCT05243550