FDA Grants Priority Review to UGN-101 for Low-Grade Upper Tract Urothelial Cancer

The FDA has granted apriority review designation to the new drug application(NDA) for UGN-101 (mitomycin gel) for the potential treatment of patients with low-grade upper tract urothelial cancer (LG UTUC), UroGen Pharma Ltd., announced in a press release.

Should the NDA be approved, the investigational drug formulation of mitomycin will be the first nonsurgical treatment option for patients with LG UTUC. The agent has previously received Orphan Drug, Fast Track, and Breakthrough Therapy designations from the FDA for the treatment of LG UTUC.

“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,” said Liz Barrett, president and chief executive officer of UroGen. “There is a significant unmet need for a better treatment option for patients with LG UTUC, as the current standard of care involves surgical removal of the kidney or repetitive endoscopic tumor removal.”

The designation was based on data from the phase III OLYMPUS trial. This pivotal, open-label, single-arm study evaluated the safety, tolerability, and tumor ablative effect of UGN-101 in patients with LG UTUC.

According toresults from the OLYMPUS trial, the complete response (CR) rate was 59%. After 6 months of follow-up, 89% of patients maintained response, and after 12 months of follow-up, 84% of patients had durability of their response after primary disease evaluation (PDE). The estimated time to recurrence was 13.0 months.

By physician assessment, 34 patients were characterized as having endoscopically unresectable tumor at baseline, and 20 of these patients achieved a CR as of the PDE.

The most common treatment-emergent adverse events (TEAEs) included ureteral stenosis, urinary tract infection, hematuria, flank pain, dysuria, renal impairment, hydronephrosis, and frequency. Most of the TEAEs were transient and considered mild to moderate in severity. The most common grade 3 TEAEs were ureteral stenosis (8.5%) and hematuria, flank pain, and urinary tract infection (3% each). Additionally, 1 grade 4 event of subdural hematoma occurred.

Adverse events involving the renal or urinary tract occurred in 67% of patients in the study and required a temporary ureteral stent placement in 50%, a long-term ureteral stent in 23%, and nephroureterectomy in 4%.

Overall, 74 patients were enrolled across multiple sites in the United States and Israel. Patients were treated with 6 weekly installations of UGN-101 via a standard catheter. Patients underwent a PDE approximately 4 to 6 weeks after their last installation to determine rates of CR, which was the primary end point of the study. Patients who achieved a CR at the PDE timepoint were followed for up to 1 year to determine the durability of the study drug.

To be included in the trial, patients had to have naïve or recurrent noninvasive LG UTUC and at least 1 measurable papillary LG tumor of ≤15 mm. If patients had received a Bacillus Calmette-Guérin treatment for urothelial carcinoma within 6 months of their first study visit or had untreated concurrent urothelial carcinoma in other locations outside of the targeted area, they could not be included in the study.

The FDA has set a Prescription Drug Fee Act action date of April 18, 2020. The company is currently on track for the potential launch of UGN-101 for the treatment of LG UTUC by mid-2020.

Reference:

UroGen Pharma Announces FDA Filing Acceptance and Priority Review of U.S. New Drug Application (NDA) for UGN-101 [press release]. New York, New York:UroGen Pharma Ltd.; December 19, 2019. https://bwnews.pr/2Z2klJh. Accessed December 19, 2019.