FDA Approves First Therapy for Treatment of Low-Grade Upper Tract Urothelial Cancer

FDA News Release

• For Immediate Release: April 15, 2020

Today, the U.S. Food and Drug Administration approved Jelmyto (mitomycin gel), the first therapy to treat low-grade upper tract urothelial cancer (UTUC). Urothelial cancer is a cancer of the lining of the urinary system.

“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,” said Richard Pazdur, M.D., 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. “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.”

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 (the long, thin tube that connects that kidney to the bladder). 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.”

Jelmyto is an alkylating drug, meaning it inhibits the transcription of DNA into RNA, stopping protein synthesis and taking away the cancer cell’s ability to multiply. The FDA approved Jelmyto based on the results of a clinical trial involving 71 patients with low-grade UTUC. These patients had never undergone treatment or had recurrent low-grade non-invasive UTUC with at least one measurable papillary tumor (a tumor shaped like a small mushroom with its stem attached to the inner lining of an organ). Patients received Jelmyto once a week for six weeks and, if assessed as a complete response (complete disappearance of the papillary tumor), monthly for up to 11 additional months. Efficacy of Jelmyto was evaluated using urine cytology (a test to look for abnormal cells in a patient’s urine), ureteroscopy (an examination of the upper urinary tract) and biopsy (if warranted) three months following the initiation of therapy.

The primary endpoint was complete response at three months following initiation of therapy. A complete response was found in 41 of the 71 patients (58%) following six treatments of Jelmyto administered weekly. Durability of the effect of Jelmyto in patients with a complete response was also evaluated using urine cytology, ureteroscopy and biopsy (if warranted) every three months for a year following the initiation of therapy. Nineteen patients (46%) who achieved a complete response continued to have a complete response at the 12-month mark.

Common side effects for patients taking Jelmyto were ureteric obstruction (narrowing or blockage of the ureter that may lead to excess fluid in the kidney due to a backup of urine), flank pain (pain occurring on the side of the body), urinary tract infection, hematuria (blood in the urine), renal dysfunction (inability of the kidney to function in its designed capacity), fatigue, nausea, abdominal pain, dysuria (painful or difficult urination) and vomiting.

Jelmyto can cause serious side effects including ureteric obstruction, flank pain and urosepsis (bacteria in the bloodstream from a urinary tract infection). Patients with ureteric obstruction may require transient or long-term stents to relieve this obstruction. The obstruction may be persistent and did not resolve or did not resolve completely in 51% of patients who experienced obstruction due to Jelmyto. Jelmyto should be avoided in patients with a glomerular filtration rate (a test used to check how well the kidneys are working) of less than 30mL/min.

Women who are pregnant should not take Jelmyto because it may cause harm to a developing fetus or newborn baby. The FDA advises health care professionals to tell females of reproductive age to use effective contraception during treatment with Jelmyto, and for six months following the last dose. Male patients with female partners of reproductive potential should also use effective contraception during treatment with Jelmyto and for three months following the last dose.

The FDA granted this application Priority Review and Breakthrough Therapy designation, which expedites the development and review of drugs that are intended to treat a serious condition, when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies. Jelmyto was also granted Fast Track designation, which expedites the review of drugs to treat serious conditions and fill an unmet medical need. Jelmyto received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted approval of Jelmyto to UroGen Pharma, Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.