FDA approves Mitomycin gel for treating upper tract urothelial cancer

The U.S. Food and Drug Administration has approved mitomycin gel, the first ever therapy for low-grade upper tract urothelial cancer (UTUC).

UTUC corresponds to a subset of urothelial cancers that arise in the lining of the kidney or the ureter.Low-grade UTUC is rare, but affects 6,000-8,000 new patients in the United States every year.

Jelmyto is an alkylating drug, it inhibits the transcription of DNA into RNA, stopping protein synthesis and taking away the cancer cell's ability to multiply.

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

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.

"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."l

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.