UroGen Announces Results from Subgroup Analyses of the Pivotal ENVISION Trial Evaluating Impact of Baseline Tumor Burden and Focality on Response to UGN-102

Rhea-AI Summary

UroGen Pharma (Nasdaq: URGN) announced results from subgroup analyses of the pivotal ENVISION trial evaluating UGN-102 for treating recurrent low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC). The study demonstrated strong complete response (CR) rates across different patient subgroups:

- 82.8% CR for patients with tumor burden ≤3 cm vs 73.2% for >3 cm
- 79.3% CR for patients with multiple tumors vs 82.9% for single tumors

The ENVISION trial included 240 patients, with 95% receiving all six weekly intravesical instillations. The overall CR rate was 79.6% at three months, with 82.3% probability of maintaining response after 12 months. UroGen completed its NDA submission to the FDA with a PDUFA date of June 13, 2025. A separate ATLAS trial analysis showed UGN-102 reduced risk of recurrence, progression or death by 54% compared to TURBT.

Positive

• High complete response rates across all patient subgroups (73.2-82.9%)
• 82.3% probability of maintaining response after 12 months
• 54% decreased risk of recurrence compared to standard treatment (TURBT)
• NDA submission completed ahead of schedule

Negative

• 15.4-20% of patients experienced disease recurrence, progression, or death by 15 months
• Study limitations include small sample size of comparator groups
• Multiple adverse events reported including dysuria, hematuria, and urinary tract infection

Insights

Medical Research Analyst

The ENVISION trial subgroup analyses reveal compelling efficacy data that significantly strengthen UGN-102's regulatory and commercial prospects. The high complete response rates across different tumor burdens (82.8% for ≤3 cm and 73.2% for >3 cm) demonstrate remarkable consistency, suggesting broad applicability across the patient population. This is particularly significant as tumor burden often impacts treatment efficacy in oncology.

The durability of response is especially noteworthy, with only 15.4% to 20.0% of patients experiencing disease recurrence, progression, or death by 15 months post-treatment. This compares favorably to historical recurrence rates with standard TURBT procedures, which can exceed 50% within one year. The ATLAS trial's demonstration of a 54% reduced risk of recurrence versus TURBT provides compelling evidence for UGN-102's superior efficacy.

The safety profile appears manageable, with primarily mild-to-moderate adverse events that resolve over time. The consistent safety data across multiple trials strengthens the regulatory package. With the NDA submission completed and a PDUFA date set for June 13, 2025, UroGen is well-positioned for potential commercialization in the second half of 2025.

The positive data across both ENVISION and ATLAS trials, combined with the unmet need in LG-IR-NMIBC, suggests significant market potential. The ability to reduce repeated surgical interventions could drive strong adoption among both physicians and patients, potentially establishing UGN-102 as a new standard of care in this indication.

• Results presented at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium (ASCO GU 2025)
• Treatment with UGN-102 resulted in durable complete response (CR) rates across subgroups with recurrent low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC)
• CR rates were:
  • 82.8% for patients with a tumor burden ≤3 cm compared to 73.2% for those with a tumor burden >3 cm
  • 79.3% for patients with multiple tumors compared to 82.9% for those with single tumors
• CR rates and duration of response (DOR) patterns were similar across tumor burden and focality subgroups

PRINCETON, N.J.--(BUSINESS WIRE)-- UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, today announced results from the subgroup analyses of the pivotal ENVISION study evaluating the impact of tumor burden and focality on the response to UGN-102, an investigational drug in development for treatment of LG-IR-NMIBC. Analyses of pre-specified subgroups showed comparable CR rates and DOR patterns across different levels of tumor burden (defined as the sum of the diameters of all visible tumors) and number of tumors at baseline in patients treated with UGN-102. The poster presentation titled, Impact of Tumor Burden or Focality in Recurrent Low-Grade Intermediate-Risk Non-Muscle-Invasive Bladder Cancer on Response to Treatment with UGN-102: A Substudy of the Phase 3 ENVISION Trial was presented today at ASCO GU 2025.

"In this subgroup analysis on tumor burden and focality from the ENVISION study, the overall CR rate was consistent, and a majority of patients maintained their response 12 months after achieving CR at three months," said Sandip M. Prasad, M.D., Director of Urology at Morristown Medical Center and lead author of the study. "These results provide evidence of UGN-102’s potential to become an effective and durable treatment option for patients with recurrent LG-IR-NMIBC, regardless of tumor size or focality."

The ENVISION study included 240 patients with recurrent LG-IR-NMIBC who received at least one dose of UGN-102 and 95% (228 patients) received all six weekly intravesical instillations of UGN-102. In this pre-specified analysis CR rates were 82.8% for patients with a tumor burden ≤3 cm (n=149/180) compared to 73.2% for those with a tumor burden >3 cm (n=30/41). Of the patients with CR at three months, 15.4% vs 20.0% experienced recurrence of low-grade disease, progression (either in stage or grade), or death (unrelated to treatment) by 15 months. In the 191 patients with multiple vs single tumors who achieved a CR, the three-month CR was 79.3% vs 82.9%, with recurrence rates of 18.5% vs 11.8%.

“We are encouraged by these results, which highlight the potential of UGN-102 to provide durable responses in patients with recurrent LG-IR-NMIBC,” said Mark Schoenberg, M.D., Chief Medical Officer of UroGen. “These pre-specified subgroup analyses further strengthen the growing body of evidence supporting UGN-102 as a treatment option for patients dealing with the challenges of disease recurrence and the need for repeated surgeries.”

The ENVISION trial’s primary efficacy and safety results, previously presented, showed that UGN-102 delivered a 79.6% CR rate at three months, with an unprecedented 82.3% probability of remaining in response 12 months later by Kaplan-Meier estimates.

These findings further support UGN-102’s potential to alter the treatment landscape for patients with LG-IR-NMIBC, a condition where recurrence and progression remain significant clinical challenges.

UroGen initiated the submission of a rolling new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for UGN-102 as a treatment for LG-IR-NMIBC in January 2024 and completed the NDA submission in August, ahead of schedule. The FDA accepted the NDA for UGN-102 with a Prescription Drug User Fee Act (PDUFA) goal date of June 13, 2025.

The most common treatment-emergent adverse events (TEAEs) in the ENVISION trial were dysuria, hematuria, urinary tract infection, pollakiuria, fatigue, and urinary retention. The TEAEs were typically mild-to-moderate in severity and either resolved or were resolving. The ENVISION trial demonstrated a similar safety profile to that observed in other studies of UGN-102.

Study limitations include the small sample size of the comparator groups and the single arm design.

The analysis in another presentation titled, Treatment of Low-Grade Intermediate-Risk Non-Muscle-Invasive Bladder Cancer with UGN-102: Results of the Phase 3 ATLAS and ENVISION Studies highlights that in both studies, the CR rate in patients initially treated with UGN-102 was robust, with the majority of patients remaining event-free at 12 months after a three-month CR. A new analysis from the ATLAS trial highlights 54% decreased risk of recurrence, progression or death with UGN-102 compared to TURBT. The hazard ratio for DOR in ATLAS was 0.46 with a 95% confidence interval (0.24, 0.86) favoring the UGN-102 arm. Median DOR was not estimable in any arm due to low recurrence rates; the most common adverse event with UGN-102 in both studies was dysuria, occurring in 22.5% in ENVISION and 30.4% in ATLAS.

About UGN-102

UGN-102 (mitomycin) for intravesical solution is an innovative drug formulation of mitomycin, currently in Phase 3 development for the treatment of LG-IR-NMIBC. Utilizing UroGen’s proprietary RTGel^® technology, a sustained release, hydrogel-based formulation, UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-102 is delivered to patients using a standard urinary catheter in an outpatient setting by a trained healthcare professional. UroGen completed the NDA submission in August, ahead of schedule. The FDA accepted the NDA for UGN-102 and assigned a PDUFA goal date of June 13, 2025.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

In the U.S., bladder cancer is the second most common urologic cancer in men. LG-IR-NMIBC represents approximately 23,000 newly diagnosed bladder cancer patients each year and an estimated 59,000 recurrences annually among patients diagnosed in previous years. Bladder cancer primarily affects older populations with increased risk of comorbidities, with the median age of diagnosis being 73 years. Guideline recommendations for the management of NMIBC include trans-urethral resection of bladder tumor (TURBT) as the standard of care. Up to 70 percent of NMIBC patients experience at least one recurrence and LG-IR-NMIBC patients are even more likely to recur and face repeated TURBT procedures.

About ENVISION

The Phase 3 ENVISION trial is a single-arm, multinational, multicenter study evaluating the efficacy and safety of UGN-102 (mitomycin) for intravesical solution as a chemoablative therapy in patients with LG-IR-NMIBC. The Phase 3 ENVISION trial completed target enrollment with approximately 240 patients across 56 sites. Study participants received six once-weekly intravesical instillations of UGN-102. The primary endpoint evaluated the CR rate at the three-month assessment after the first instillation, and the key secondary endpoint evaluated durability over time in patients who achieved a CR at the three-month assessment. Learn more about the Phase 3 ENVISION trial at www.clinicaltrials.gov (NCT05243550).

About UroGen Pharma Ltd.

UroGen is a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers because patients deserve better options. UroGen has developed RTGel reverse-thermal hydrogel, a proprietary sustained-release, hydrogel-based platform technology that has the potential to improve the therapeutic profiles of existing drugs. UroGen’s sustained release technology is designed to enable longer exposure of the urinary tract tissue to medications, making local therapy a potentially more effective treatment option. Our first product to treat low-grade upper tract urothelial cancer and investigational treatment UGN-102 (mitomycin) for intravesical solution for patients with LG-IR-NMIBC are designed to ablate tumors by non-surgical means. UroGen is headquartered in Princeton, NJ with operations in Israel. To learn more, visit www.UroGen.com or follow us on X (Twitter), @UroGenPharma.

Forward-Looking Statements

This press release contains forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, statements regarding: the ENVISION subgroup analyses providing evidence of UGN-102's potential to become an effective and durable treatment option for patients with recurrent LG-IR-NMIBC, regardless of tumor size or focality and further strengthening the growing body of evidence supporting UGN-102 as a treatment option for patients dealing with the challenges of disease recurrence and repeated surgeries; the potential benefits to patients and opportunities for UGN-102, if approved, including to alter the treatment landscape for patients with LG-IR-NMIBC; statements related to UroGen’s NDA submission and expected PDUFA target action date for UGN-102; the estimated annual U.S. patient population and demographics for LG-IR-NMIBC; the potential of UroGen’s proprietary RTGel technology to improve therapeutic profiles of existing drugs; and UroGen’s sustained release technology making local delivery potentially more effective as compared to other treatment options. These statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to: prior results may not be indicative of results that may be observed in the future; even though the NDA for UGN-102 has been accepted for filing by the FDA, there is no guarantee that such NDA will be sufficient to support approval of UGN-102 on the timeframe expected, or at all; the ability to maintain regulatory approval; complications associated with commercialization activities; the labeling for any approved product; competition in UroGen’s industry; the scope, progress and expansion of developing and commercializing UroGen’s product candidates; the size and growth of the market(s) therefor and the rate and degree of market acceptance thereof vis-à-vis alternative therapies; UroGen’s ability to attract or retain key management, members of the board of directors and other personnel; UroGen’s RTGel technology may not perform as expected; and UroGen may not successfully develop and receive regulatory approval of any other product that incorporates RTGel technology. In light of these risks and uncertainties, and other risks and uncertainties that are described in the Risk Factors section of UroGen’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, filed with the SEC on November 6, 2024 (which is available at www.sec.gov), the events and circumstances discussed in such forward-looking statements may not occur, and UroGen’s actual results could differ materially and adversely from those anticipated or implied thereby. Any forward-looking statements speak only as of the date of this press release and are based on information available to UroGen as of the date of this release.

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INVESTOR CONTACT:

Vincent Perrone

Senior Director, Investor Relations

vincent.perrone@urogen.com

609-460-3588 ext. 1093



MEDIA CONTACT:

Cindy Romano

Director, Corporate Communications

cindy.romano@urogen.com

609-460-3583 ext. 1083

Source: UroGen Pharma Ltd.

FAQ

What were the complete response rates for UGN-102 in the ENVISION trial for URGN?

The ENVISION trial showed complete response rates of 82.8% for patients with tumor burden ≤3 cm and 73.2% for >3 cm, while patients with multiple tumors achieved 79.3% CR versus 82.9% for single tumors.

When is the PDUFA date for UroGen's UGN-102 (URGN)?

The FDA set a PDUFA goal date of June 13, 2025, for UroGen's UGN-102 NDA submission.

How does UGN-102 compare to TURBT in the ATLAS trial for URGN stock?

The ATLAS trial showed UGN-102 reduced the risk of recurrence, progression, or death by 54% compared to TURBT, with a hazard ratio of 0.46.

What are the main side effects of UGN-102 reported in the ENVISION trial?

The most common side effects were dysuria, hematuria, urinary tract infection, pollakiuria, fatigue, and urinary retention, typically mild-to-moderate in severity.

What is the durability of response for UGN-102 in the ENVISION trial?

Patients who achieved complete response at three months showed an 82.3% probability of maintaining response after 12 months according to Kaplan-Meier estimates.