UGN-103 under development for urothelial cancers
A phase 3 study is expected to initiate in 2024 to explore the safety and efficacy of UGN-103 in LG-IR-NMIBC.
UroGen Pharma has entered into a licensing agreement with medac GmbH to develop UGN-103, a next-generation novel mitomycin-based formulation for the treatment of patients with urothelial cancers, according to a news release from UroGen Pharma.1
UroGen plans to submit a New Drug Application in 2024 and anticipates an FDA decision in 2025 for UGN-102.
UGN-103 combines UroGen’s RTGel technology with medac GmbH’s mitomycin. The formulation, if approved, is expected to provide advantages in regard to production, cost, supply, and product convenience. A phase 3 study is expected to initiate in 2024 to explore the safety and efficacy of UGN-103 for the treatment of patients with low-grade intermediate-risk non–muscle-invasive bladder cancer (LG-IR-NMIBC).
"The strategic alliance with medac fortifies our commitment to continuously innovate novel, non-surgical treatments for patients with urothelial cancers, including LG-IR-NMIBC,” said Liz Barrett, president and CEO of UroGen, in the news release.1 "The 80 mg formulation of mitomycin from medac is specifically designed to be mixed with our RTGel technology, which may provide advantages for patients looking for non-surgical treatments for urothelial cancer. With medac's intellectual property protection for this next-generation mitomycin formulation lasting until June 2035 and our pending U.S. patent applications, we foresee potential intellectual property protection until December 2041."
Development of UGN-103 is anticipated to initiate following the approval and launch of UGN-102, according to UroGen.
Data on UGN-102
UGN-102 (mitomycin) for intravesical solution is a hydrogel-based formulation being investigated for use in patients with LG-IR-NMIBC. The treatment is currently being assessed in the phase 3 ENVISION trial (NCT05243550).
According to findings presented at the 2023 Society of Urologic Oncology Annual Meeting, interim data from the trial showed a complete response rate of 79.2% (95% CI, 73.5-84.1) with UGN-102 at 3-month follow-up.2 In the remaining patients, 14.6% had residual disease, 2.5% progressed to high-grade disease, 1.7% had an indeterminate response, and 2.1% did not have data.
Regarding safety, nearly all treatment-emergent adverse events (TEAEs) were mild or moderate. TEAEs occurring in at least 5% of patients included dysuria (17.9% mild; 3.8% moderate), hematuria (6.3% mild; 2.1% moderate), pollakiuria (5.4% mild; 0.8% moderate), urinary tract infection (1.7% mild; 4.2% moderate), and fatigue (3.8% mild; 1.7% moderate). One patient had severe dysuria.
Overall, the study included 240 patients with LG-IR-NMIBC. Patients received primary chemoablative therapy with UGN-102 as 6 once-weekly intravesical instillations administered using a traditional urethral catheter. Nearly all patients (95%) received the full 6 instillations of UGN-102.
The study’s primary end point was the complete response rate at 3 months following the initial treatment instillation. Secondary outcome measures include the duration and durability of response, as well as disease-free survival.3
UroGen plans to submit a New Drug Application in 2024 and anticipates an FDA decision in 2025 for UGN-102 pending positive results on the durability of response end point from the ENVISION trial.
References
1. UroGen secures exclusive license from medac GmbH to develop a next-generation novel mitomycin-based formulation for urothelial cancers. News release. UroGen Pharma. Published online and accessed January 17, 2024. https://www.biospace.com/article/releases/urogen-secures-exclusive-license-from-medac-gmbh-to-develop-a-next-generation-novel-mitomycin-based-formulation-for-urothelial-cancers/?s=86
2. Prasad S, Mladenov B, Shishkov D, et al. Primary chemoablation for recurrent low grade intermediate risk (LG IR) NMIBC: the ENVISION trial. Presented at: 2023 Society of Urologic Oncology Annual Meeting. November 28 – December 1, 2023; Washington, DC. LBA 3389
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 September 29, 2023. Accessed January 17, 2024. https://clinicaltrials.gov/study/NCT05243550
Speaking of Urology Podcast: Dr. Ritch and Dr. Katz discuss new bladder cancer management app
December 7th 2021“It's not a replacement for clinical judgment, obviously. But at the end of the day, the idea is that it shows you what your next steps are based on what the American Urological Association and [Society of Urologic Oncology] guidelines are for non-muscle invasive bladder cancer,” Chad R. Ritch, MD, MBA, FACS.
Nadofaragene firadenovec shows durable efficacy in NMIBC
April 8th 2024"In this follow-up analysis of the phase 3 study, we demonstrated a sustained response to Adstiladrin treatment over 3 years, allowing more than half of the patients in the study to remain cystectomy free for at least 36 months,” says Colin P.N. Dinney, MD.
