FDA Grants Priority Review to UGN-101 for Urothelial Cancer


The FDA has granted a priority review designation to a new drug application for UGN-101 for the treatment of patients with low-grade, upper tract urothelial cancer.

Liz Barrett, president and chief executive officer of UroGen Pharma

Liz Barrett, president and chief executive officer of UroGen Pharma

Liz Barrett

The FDA has granted a priority review designation to a new drug application (NDA) for UGN-101 (mitomycin gel) for the treatment of patients with low-grade, upper tract urothelial cancer (UTUC).1

The designation is based on results from the pivotal phase III OLYMPUS trial, in which a final analysis showed that UGN-101 elicited a complete response (CR) rate of 59% in this patient population. Under the Prescription Drug User Fee Act, the FDA must make a decision on the application by April 18, 2020.

“The FDA filing acceptance and granting of priority review for UGN-101 is an important milestone in our mission to pioneer new treatments to improve patient care in specialty cancers and urologic diseases,” Liz Barrett, president and chief executive officer of UroGen Pharma, the developer of the investigational mitomycin formulation, stated in a press release. “There is a significant unmet need for a better treatment option for patients with [low-grade upper tract urothelial cancer], as the current standard of care involves surgical removal of the kidney or repetitive endoscopic tumor removal.”

UGN-101 uses the RTGel™ technology platform and is designed to permit longer exposure of mitomycin to urinary tract tissue, which allows for the nonsurgical treatment of these tumors. The therapy is administered to patients using standard ureteral catheters.

The prospective, international, multicenter, open-label, single-arm OLYMPUS trial was designed to evaluate the efficacy, safety, and tolerability of UGN-101 in patients with low-grade UTUC. To be eligible for enrollment, adult patients had to have treatment-naïve or recurrent disease, ≥1 measurable papillary low-grade tumor ≤15 mm, and a wash urine cytology sampled from the pyelocaliceal system showing the absence of high-grade disease.

Those who previously received Bacillus Calmette-Guérin within the past 6 months, had untreated concurrent urothelial cancer in other sites aside from the target area, prior carcinoma in situ in the urinary tract, prior 5-year history of invasive urothelial carcinoma in the urinary tract, prior 2-year history of high-grade papillary urothelial carcinoma in the urinary tract, or is actively being treated or intends to be treated with chemotherapy are excluded.

Investigators enrolled 71 patients with low-grade UTUC who received 4 mg mitomycin C (MMC) concentration per 1 mL of TC-3 gel, with a maximum dose of 15 ml for 6 once-weekly intravesical instillations. The co-primary endpoints were CR, which was defined as a negative ureteroscopic evaluation and negative wash cytology and adverse events rate.

Moreover, patients in CR will receive UGN-101 once monthly as maintenance treatment for 11 instillations or the first recurrence, whichever comes first.

Secondary endpoints included long-term durability of CR, CR rate at 3, 6, and 9 months after evaluation, partial response, MMC level in the plasma for select patients.

Sixty-one patients were evaluated for CR; primary disease evaluation is awaited in the remaining 10 patients. Previously announced results also showed that 45% of tumors were found to be unresectable by surgery at baseline.2

The results of the final analysis also showed that, by Kaplan Meier analysis, the durability of response was approximately 89% at 6 months and 84% at 12 months; the median time to recurrence was estimated to be 13 months.

Regarding safety, the most commonly reported treatment-emergent adverse events were ureteric stenosis (43.7%), urinary tract infection (32.4%), hematuria (31.0%), flank pain (29.6%), nausea (23.9%), dysuria (21.1%), renal impairment (19.7%), and vomiting (19.7%). A total 8.5% of patients reported severe events of ureteric stenosis.

In an interim analysis of the OLYMPUS study of 28 evaluable patients, the CR rate in the intent-to-treat (ITT) cohort was 57%, with 5 patients who had not undergone their assessment.3 At the time 6 patients underwent 3-month follow-up and remained in CR.

Previously, the FDA granted UGN-101 orphan drug designation, fast track designation, and, in October 2018, a breakthrough therapy designation for UGN-101 in this setting.


  1. UroGen Pharma Announces FDA Filing Acceptance and Priority Review of U.S. New Drug Application (NDA) for UGN-101 [news release]. UroGen Pharma. Published December 19, 2019. Accessed December 19, 2019.
  2. UroGen Pharma Announces Positive Results of UGN-101 from Pivotal Phase 3 OLYMPUS Trial for the Non-Surgical Treatment of Patients with Low-Grade Upper Tract Urothelial Cancer (LG UTUC). UroGen Pharma Ltd. Published January 8, 2019.". Accessed January 8, 2019.
  3. Kleinmann N, Pierorazio P, Matin S, et al. Non-surgical management of low grade upper tract urothelial cancer: an interim analysis of the international multicenter OLYMPUS trial (NCT02793128). J Urol. 2018;199(4S):e1166. doi: 10.1016/j.juro.2018.03.097.
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