Upper Tract Urothelial Carcinoma (UTUC) refers to malignant changes of the transitional urothelial cells lining the upper urothelial tract of the renal pelvis and ureter. UTUC typically exhibits high local recurrence and development of metastases. Similar to NMIBC, the prognosis of patients with UTUC correlates with the stage and grade of disease at the time of initial diagnosis. The key prognostic factor at the time of diagnosis of UTUC is whether the tumor is in the muscle-invasive or nonmuscle invasive stage. The number, size and location of tumors presented also represent important prognostic factors for UTUC. Approximately 40% of the patients diagnosed annually with UTUC in the United States present with non-muscle invasive UTUC. Non-muscle invasive UTUC is also divided into two grades, low and high. In two studies conducted in 1997 and 2003 of 30 and 20 patients with non-muscle invasive UTUC, 87% and 75% of patients were diagnosed with low-grade non-muscle UTUC, respectively.
UTUC accounts for approximately 5% to 10% of all new cases of urothelial cancer, which corresponds to an estimated annual incidence in the United States of up to 7,500 cases. In 2012, the estimated prevalence of UTUC in the United States was approximately 45,000, of which approximately 14,500 had low-grade disease. UTUC is nearly three times more common in men than women and affects mostly the elderly.
There are currently no drugs approved by the FDA for the treatment of UTUC, representing a significant unmet medical need. Moreover, the anatomical complexity of the upper urothelial tract, particularly the renal pelvis, presents significant challenges to the proper identification and ability to reach and resect all tumors in tumor resection surgical procedures. Consequently, patients with high-grade disease or patients with low-grade disease that present with a large number of tumors typically undergo nephroureterectomy, which is kidney and upper urothelial tract removal. In addition, the stage and grade of UTUC are often misdiagnosed, which we believe is due to the structural complexity of the upper urothelial tract. Due to these factors, the current standard of care for the treatment of UTUC is nephroureterectomy.
UroGen is developing UGN-101, mitomycin) urothelial gel, 0.4%, an investigational new drug formulation of mitomycin being developed for the treatment of Upper Tract Urothelial Cancer (UTUC). UGN-101 is formulated using UroGen’s proprietary reverse thermal gel technology, RTGEL™.
RTGEL is a gel technology which is liquid at lower temperatures but converts to a semi-solid state at body temperature. The liquid characteristics are thought to aid in drug delivery while the conversion to the semisolid state following instillation is believed to result in longer retention of the mitomycin in the upper urinary tract compared to regular instillation. The RTGEL is water soluble and dissolves over time upon contact with urine, which is thought to enable a prolonged exposure of tumor tissue to mitomycin.
The Company is researching whether the use of RTGel with mitomycin causes a substantial increase in dwell time of mitomycin. If clinical trials demonstrate that this does in fact occur, UGN-101 may have the potential to be a first-line chemoablation treatment for low-grade UTUC, potentially sparing patients from repeated surgeries and potentially reducing the need for kidney and upper urothelial tract removal.
The Orphan Drug Designation granted to UGN-101for the treatment of UTUC could result in marketing exclusivity for seven years following approval by the FDA, if granted. In addition, this drug candidate has been a “Fast Track” designation that means the New Drug Application (NDA) will be given a priority review.
UroGen has recently started the OLYMPUS study, a multicenter clinical trial to evaluate the safety and efficacy of UGN-101 for the treatment of low grade UTUC. Read more on the OLYMPUS trial
To learn more about UTUC and the OLYMPUS trial please watch the BCAN Webinar hosted by Dr. Gary Steinberg held on Nov 14th. Click here.