SILVER SPRING, Md. and PRINCETON, N.J.—Today the U.S. Food and Drug Administration (FDA) approved Jelmyto (mitomycin gel), which is the first therapy to treat low-grade upper tract urothelial cancer (UTUC). The FDA granted the approval to UroGen Pharma, Inc.
“UroGen was founded on the vision to improve lives by challenging the current standard of care. Jelmyto, which leverages our innovative technology and expertise in specialty cancers and urologic diseases, is just the beginning as we build a company focused on bringing novel solutions to patients,” said Liz Barrett, president and chief executive officer of UroGen in a company press release.
Jelmyto is an alkylating drug that inhibits the transcription of DNA into RNA, stopping protein synthesis and taking away the cancer cell’s ability to multiply. Jelmyto combines mitomycin and a sterile hydrogel, using UroGen’s proprietary sustained release RTGel technology. It has been designed to enable longer exposure of urinary tract tissue to mitomycin.
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 is a challenging condition to treat due to the complexity of the urinary tract system. 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, but they often recur.
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. The current standard of care includes multiple surgeries, and most patients require a radical nephroureterectomy. Treatment is further complicated by the fact that UTUC is most commonly diagnosed in patients over 70 years of age, who may already have compromised kidney functionality and may suffer further complications as a result of major surgery. Low-grade UTUC is rare, but it affects 6,000-8,000 new patients in the U.S. 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. 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,” noted 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. “Jelmyto gives patients, for the first time, an alternative treatment option for low-grade UTUC.”
The FDA’s efficacy determination was based on the OLYMPUS (NCT02793128) trial. OLYMPUS evaluated 71 patients with treatment-naive 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 undergone prior tumor debulking.
Patients received weekly Jelmyto 4 mg per mL treatments via ureteral catheter or nephrostomy tube for 6 weeks. The primary endpoint was complete response (CR) at three months following initiation of therapy. For patients with a CR at 3 months, treatments were administered monthly for a maximum of 11 additional treatments. A CR was found in 41 patients (58%), following six weekly treatments of Jelmyto; 29 patients received at least one dose of maintenance therapy.
Durability of the effect of Jelmyto in patients with a complete response was 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, flank pain, urinary tract infection, hematuria, renal dysfunction, fatigue, nausea, abdominal pain, dysuria and vomiting. Ureteric obstruction occurred in 58% of those receiving Jelmyto, and required ureteral stent placement in 88% of these patients.
“This novel, minimally invasive, kidney-sparing treatment has the potential to transform the way low-grade upper tract urothelial cancer is treated and help patients avoid long-term complications associated with surgery and the loss of their kidney,” added Dr. Seth Lerner, M.D., FACS, professor of Urology at Baylor College of Medicine and principal investigator of the OLYMPUS trial.
“We thank the patients and researchers involved in our OLYMPUS trial for helping us advance a transformative treatment in a disease space that has been historically ignored,” Barrett stated. “We are tremendously proud to have pioneered this first-in-class therapy that improves patient care in a difficult-to-treat cancer.”