Intravesical Paclitaxel for the treatment of Upper Tract Urothelial Carcinoma (UTUC)

UTUC is estimated to have a prevalence of 45,000 patients in the U.S. with four times higher prevalence rates in some Asian countries. There are currently no drugs approved for the treatment of UTUC, and the complexity of the upper urothelial tract presents significant challenges to reaching and surgically resecting all tumors.

UTUC-1005 is based on a similar formulation to TBC-1002. Following the completion of the TBC-1002 Phase 1/2A studies,  a Phase 2 clinical trial with UTUC-1005 will be initiated.

Typically, patients with high or low grade UTUC exhibiting multiple tumors undergo kidney and upper urothelial tract removal (nephroureterectomy). If approved, UTUC-1005 could be the first formulated and approved treatment for UTUC that could provide an alternative for these patients.

It is likely that UTUC-1005 will receive Orphan Drug Designation for the treatment of UTUC in the U.S. and the European Union. Such designations will make UTUC-1005 eligible for seven years of exclusivity from approval in the United States, and ten years of exclusivity in the European Union.

An Orphan disease

Upper tract urothelial carcinoma (UTUC) is an uncommon disease accounting for 5-10 percent of urothelial carcinomas with 6,000 cases per year in the U.S. alone. Western countries have an overall incident rate of approximately two out of every 100,000 inhabitants. Eastern countries record up to double that rate. UTUC is highly recurrent, with 15-50 percent of tumors recurring after surgical management and 8.5-13 percent of UTUC cases being concurrent with bladder cancer. UTUC is more prevalent in the elderly and affects three times more men than women.

The European Association of Urology Standard of Care (SOC) and the U.S. National Comprehensive Cancer Network (NCCN) guidelines recommend first stratifying by risk, then kidney-sparing surgery for low risk patients and Radical Nephroureterectomy (RNU) for high risk patients. Patients are high risk where the disease has already invaded the muscle with number, size and location of tumors being prognostic factors. In 2012, the estimated prevalence of UTUC in the U.S.A. was approximately 45,000, of which 60 percent were diagnosed with high risk disease.

Significant unmet medical needs

There are currently no drugs formulated or approved by the FDA for the treatment of UTUC. The current standards of care entail kidney sparing surgery for low risk patients and RNU for high risk patients with adjuvant post-operative chemotherapy believed to reduce disease-free survival (DFS) rates.

In the U.S., patients who undergo RNU and adjuvant chemotherapy cost society more than $38,000, taking into account loss of work and decreased quality of life. Patients that develop Chronic Kidney Disease incur an additional $89,000 per year for dialysis and a one-time $15,000 cost for fistula placement. An effective treatment that could preserve more kidneys and reduce recurrence could greatly improve the quality of life in patients and lower the overall cost of treatment.