On April 15, 2020, the FDA approved mitomycin gel (Jelmyto; UroGen Pharma), an alkylating drug as the first treatment for patients with low-grade upper-tract urothelial cancer. Mitomycin is a combination of chemotherapy and a sterile hydrogel that stops the transcription of DNA into RNA and halts the synthesis of protein, thereby blocking the ability of cancer cells to multiply. The FDA granted mitomycin gel priority review, breakthrough therapy, fast track, and orphan drug designations.
“This is the first approval specifically for patients with low-grade UTUC [upper-tract urothelial cancer] and provides an option for some patients who may otherwise require a nephroureterectomy,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence.
“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,” Dr Pazdur added.
Upper-tract urothelial cancer is a rare cancer of the lining of the urinary system that is diagnosed in approximately 6000 to 8000 patients in the United States annually. Although the majority of urothelial cancers occur in the bladder, upper-tract urothelial cancer is part of a group of urothelial cancers that arise in the lining of the kidney or the ureter. Upper-tract urothelial cancer, which can be low-grade or high-grade, can result in impairment of kidney function in some patients.
The FDA approval of mitomycin gel was based on the results of the open-label, single-arm, phase 3 clinical trial known as OLYMPUS. The study included 71 patients with upper-tract urothelial cancer. All patients were either treatment-naive or had recurrent low-grade upper-tract urothelial cancer with at least 1 measurable papillary tumor. The patients received mitomycin gel once weekly for 6 weeks; in patients who achieved a complete response, the treatment was given on a monthly basis for up to 11 additional months.
The primary end point was complete response after 3 months of therapy. Of the 71 patients in the trial, 41 (58%) had a complete response after 6 months of weekly treatments and 19 (46%) continued to have a complete response after the 12-month mark.
The most common (≥20%) adverse events were ureteric obstruction, flank pain, urinary tract infection, hematuria, renal dysfunction, fatigue, nausea, abdominal pain, dysuria, and vomiting. Serious adverse reactions, which included ureteric obstruction, flank pain, and urosepsis, occurred in 37% of patients. Of the patients with ureteric obstruction that resulted from treatment with mitomycin gel, 51% had obstruction that persisted or did not resolve completely.
Jelmyto should not be used in patients with a glomerular filtration rate of <30 mL/min. Women who are pregnant should not take this drug, which can cause harm to a fetus or a newborn baby.
Mitomycin gel is indicated for pyelocalyceal use only and is not intended for intravenous use, topical use, or oral administration. In patients who have a complete response after 3 months of initiating treatment with mitomycin gel, additional instillations may be administered once monthly for a maximum of 11 additional instillations.