FDA has approved mitomycin (Jelmyto) for adult patients with low-grade upper tract urothelial cancer.
UroGen Pharma sponsors the drug.
“Although our nation’s emphasis is on the need to combat COVID-19, patients with cancer and their unique needs continue to be a top priority for the FDA,” Richard Pazdur, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement. “We continue to expedite oncology product development in this critical time. Our staff is continuing to meet virtually with drug developers, academic investigators and patient advocates to push forward the coordinated review of drugs, biologics and devices for cancer.”
Efficacy determination was based on OLYMPUS (NCT02793128), an ongoing, single-arm, multicenter trial enrolling 71 patients with treatment-naïve or recurrent low-grade non-invasive UTUC with at least one measurable papillary tumor located above the ureteropelvic junction. Patients who had larger tumors could have had prior tumor debulking. Patients received weekly Jelmyto 4 mg per mL instillations via ureteral catheter or nephrostomy tube for 6 weeks. For patients with a complete response at 3 months, instillations were to be administered monthly for a maximum of 11 additional instillations.
While the majority of urothelial cancers occur in the bladder, UTUC corresponds to a subset of urothelial cancers that arise in the lining of the kidney or the ureter. UTUC can block the ureter or kidney, causing swelling, infections and impairment of kidney function in some patients. UTUCs can develop as low-grade or high-grade tumors. In general, low-grade tumors are not invasive and very rarely spread from the kidney or ureter.
However, they often recur and management involves treating visible tumors and trying to preserve the urinary tract, as these tumors are more likely to recur in the urinary system than they are to spread. Low-grade UTUC is rare, but affects 6,000-8,000 new patients in the United States every year.
“This is the first approval specifically for patients with low-grade UTUC and provides an option for some patients who may otherwise require a nephroureterectomy,” said Pazdur. “Due to substantial treatment challenges associated with the complex anatomy of the upper urinary tract, many patients need to be treated with radical surgery – usually complete removal of the affected kidney, ureter and bladder cuff. Jelmyto gives patients, for the first time, an alternative treatment option for low-grade UTUC.”
The major efficacy outcome measures were CR and CR durability. CR was defined as complete absence of tumor lesions 3 months after Jelmyto initiation and was assessed by urine cytology and ureteroscopy. If warranted, a biopsy was performed. Forty-one patients (58%) achieved a CR three months following treatment initiation and were continued in follow-up; 29 patients received at least one dose of maintenance therapy.
Durability of response in those with CRs was evaluated at 3, 6, 9 and 12 months, following the CR determination.Seven patients had documented recurrences and nineteen patients remained in CR at 12-months following CR determination. The median response duration had not been reached (range: 0, 18.8+ months).
