UroGen Pharma Ltd. highlights results from a retrospective multi-center study of 32 patients evaluating the safety of antegrade administration of JELMYTO (mitomycin) for pyelocalyceal solution via percutaneous nephrostomy tube for the treatment of patients with upper tract urothelial carcinoma (UTUC). The study titled, “Antegrade Administration of Mitomycin Gel for UTUC via Percutaneous Nephrostomy Tube: A Multi-Institutional Retrospective Cohort Study,” provides additional real-world evidence of a favorable safety and tolerability profile for JELMYTO when administered via percutaneous nephrostomy tube and ispublished in The British Journal of Urology International, November Issue. This retrospective study assessed the safety and feasibility of antegrade administration of JELMYTO via a percutaneous nephrostomy tube (PCNT) in 32 patients from four institutions.

Each patient received at least one dose of JELMYTO via PCNT for UTUC, 29 of whom completed induction (at least 5 of 6 doses) and underwent primary disease evaluation (PDE) at a median 17 weeks after the last dose of therapy. At a median follow-up of 15 months following initiation of induction therapy, ureteral stenosis (defined as a discrete narrowing of the ureter on direct visual ureteroscopy, or a constriction identified on retrograde pyelogram at the time of ureteroscopy that required dilation or stenting to pass a ureteroscope for upstream visualization) occurred in three (9%) of patients. None of these patients had recurrent stenosis at a median 16 months follow- up.

Other adverse events included fatigue (27%), flank pain (19%), urinary tract infection (12%), sepsis (8%), and hematuria (8%). No patient had impaired renal function during follow-up and there were no treatment-related deaths. Seventeen patients (59%) had no evidence of disease at PDE and had not recurred at a median follow-up of 13 months post induction.

In both retrograde and antegrade approaches, JELMYTO can be administered as an outpatient procedure in the clinic. Retrograde administration requires administration by a physician via a ureteral catheter which requires fluoroscopic guidance. Antegrade administration may be performed by trained nursing professionals under clean rather than sterile conditions and does not require fluoroscopy once tube placement is confirmed via nephrostogram at the first instillation.

In this multi-center study, patients undergoing antegrade administration of JELMYTO via PCNT were retrospectively included for analysis from four tertiary referral centers between 2020 and 2022. The primary outcome was safety profile graded by Common Terminology Criteria for Adverse Events (v5.0). Post-therapy disease burden was assessed by primary disease evaluation (PDE) via ureteroscopy.

Thirty-two patients received at least one dose of JELMYTO via PCNT for UTUC, 29 of whom completed induction and underwent PDE. Thirteen (41%) patients had residual tumor present prior to induction therapy. At a median follow up of 15 months following first dose of induction therapy, ureteral stenosis occurred in 3 (9%) patients, all of which were treated without later recurrence or chronic stenosis.

Other adverse events included fatigue (27%), flank pain (19%), UTI (12%), sepsis (8%), and hematuria (8%). No patients had impaired renal function during follow up and there were no treatment related deaths. Seventeen patients (59%) had no evidence of disease at PDE and had not recurred at a median follow up of 13 months post induction.

Limitations of this study include the retrospective nature and sample size. Some complications and side effects of the antegrade approach were contingent on patient reporting, and thus may be under-reported. Ureteral stenoses were noted incidentally at the time of PDE, and no patients presented with obstructive symptoms. There is a need for larger studies with longer follow-up to study more conclusively any potential advantages of antegrade JELMYTO administration when compared to retrograde instillation.

OLYMPUS (Optimized DeLiverY of Mitomycin for Primary UTUC Study) was an open-label, single-arm Phase 3 clinical study of UGN-101 JELMYTO (mitomycin) for pyelocalyceal solution, to evaluate the safety, tolerability and tumor ablative effect of JELMYTO in patients with low-grade Upper Tract Urothelial Cancer UTUC (LG UTUC). Seventy-one patients were treated at clinical sites across the United States and Israel. Study participants were treated with six weekly instillations of JELMYTO administered via a standard catheter.

Four to six weeks following the last instillation, patients underwent a Primary Disease Evaluation (PDE) to determine Complete Response (CR), the primary endpoint of the study. PDE involved a ureteroscopy and wash cytology, a standard microscopic test of cells obtained from the urine to detect cancer and for cause biopsy. Patients who achieved a CR at the PDE timepoint were eligible for the maintenance phase of the trial, during which they could receive monthly maintenance instillations for up to 12 months and were assessed to determine the durability of response with JELMYTO.

In the OLYMPUS study, data was generated for the retrograde administration of JELMYTO. In that study, population ureteric obstruction was reported in 58% (n=41) of patients receiving JELMYTO, including 17% (n=12) of patients who experienced Grade 3 obstruction.