FDA Accepts NDA for UGN-103 in Recurrent LG-IR-NMIBC

The FDA has accepted for review a new drug application (NDA) for UGN-103, an investigational intravesical formulation of mitomycin, for adults with recurrent low-grade intermediate-risk non–muscle invasive bladder cancer (LG-IR-NMIBC).¹

The FDA set a Prescription Drug User Fee Act (PDUFA) target action date of June 14, 2027. UroGen submitted the application in August 2026, drawing on results from UTOPIA (NCT06331299), an ongoing phase 3 study. In that study, 77.8% of patients had a complete response (CR) at 3 months.² Among those with a 3-month CR, the Kaplan-Meier estimated probability of remaining event-free at 6 months was 94.5%, according to a news release from UroGen.¹

“We look forward to working closely with the FDA during its review and remain focused on delivering innovative treatment options for people living with this highly recurrent disease,” said Liz Barrett, president and CEO of UroGen, in the news release.¹

UTOPIA Trial Design

UTOPIA is a single-arm, multicenter study conducted at 30 sites in Europe and the United States. A total of 99 patients received 75 mg of UGN-103 by intravesical instillation once a week for 6 weeks, and 97% completed all 6 instillations.² The primary end point was the CR rate, meaning the share of patients with no detectable disease at the 3-month assessment by cystoscopy, for-cause biopsy, and urine cytology. Responders are being followed for up to 12 months after the 3-month visit to evaluate duration of response (DOR); safety, tolerability, and pharmacokinetics are additional secondary end points.

The median patient age was 71 years (range, 46-93), 71.7% of patients were male, and 89.2% had multiple tumors. Most patients (98.9%) had a longest tumor diameter of 3 cm or less, and 36.4% had undergone 2 or more prior transurethral resections of bladder tumor (TURBT) for low-grade NMIBC.

Efficacy Findings

As of the September 3, 2025, data cutoff, median follow-up from the start of treatment was 6.1 months. Of the 22.2% of patients who did not achieve a CR, most were assessed as having residual disease (16.2%), whereas only 4.0% had progression to high-grade disease; 2 patients had missing or indeterminate assessments. Median DOR was not yet estimable (95% CI, 0.03-2.83) at the time of the analysis, with a median DOR follow-up of 2.43 months.²

The investigators noted that the 3-month CR rate was similar to the 79.6% (95% CI, 73.9%-84.5%) rate observed with mitomycin intravesical solution (Zusduri; UGN-102) in the pivotal phase 3 ENVISION trial(NCT05243550).³ The company likewise characterized the UTOPIA efficacy and safety results as consistent with ENVISION, which led to FDA approval.¹

Safety Findings

Treatment-emergent adverse events (TEAEs) occurred in 59.6% of patients, and 5.1% had grade 3 or higher TEAEs. TEAEs were considered treatment related in 31.3% of patients and led to treatment discontinuation in 3.0%. Dysuria was the most common TEAE, reported in 19.2% of patients, followed by fatigue (9.1%), pollakiuria (8.1%), urinary tract infection (7.1%), and hematuria (6.1%).

Two patients (2.0%) had serious TEAEs, comprising atrial fibrillation, osteoarthritis, and respiratory failure, none of which were considered treatment related. No patient withdrew from the study or died because of a TEAE.

How UGN-103 Differs in Design

Compared with mitomycin intravesical solution, UGN-103 also delivers mitomycin through RTGel, UroGen's reverse-thermal, hydrogel-based platform, which is designed to prolong mitomycin exposure within the bladder. UGN-103 pairs that technology with a lyophilized mitomycin formulation. The company stated that the new formulation allows a more streamlined manufacturing process and simpler reconstitution. According to UroGen, the intravesical mitomycin solution is the only treatment the FDA has approved for this population.

Barrett described the acceptance as a step forward for the treatment of bladder cancer. “FDA acceptance of the UGN-103 NDA advances our vision for the next evolution of our portfolio and our continued commitment to transforming the treatment of recurrent LG-IR-NMIBC,” she said.

REFERENCES

1. UroGen Announces FDA Acceptance of the New Drug Application for UGN-103, an Investigational Treatment for Adults with Recurrent LG-IR-NMIBC. News release. UroGen Pharma. October 19, 2026. Accessed October 19, 2026. https://tinyurl.com/mmympnr6

2. Srivastava A, Vjaters E, Kaimakliotis HZ, et al. UTOPIA: a phase 3 trial of UGN-103, an intravesical mitomycin reverse thermal hydrogel, in recurrent low-grade intermediate-risk non-muscle invasive bladder cancer. J Clin Oncol. 2026;44(suppl 16):4604. doi:10.1200/JCO.2026.44.16_suppl.4604

3. 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. 2025;213(2):205-216. doi:10.1097/JU.0000000000004296