Intravesical Paclitaxel for the treatment of Non-Muscle Invasive Bladder Cancer ("NMIBC")
NMIBC is highly recurrent and represents 70% to 80% of all bladder cancer with more than 2.3 million patients globally. Currently available agents are not formulated nor approved for intravesical administration to prevent recurrence and progression of NMIBC. In addition, the high recurrence rate despite adjuvant intravesical treatment, strongly emphasizes the unmet need for NMIBC patients.
Paclitaxel, an agent known to be highly active in systemic application for bladder cancer, is lipophilic and not easily solubilized in the acidic bladder environment. As such, it can’t be used intravesically in its current formulation. By utilizing TesoRx's DDS to enhance permeation and solubility, TSD-001 has overcome these challenges and allows efficient intravesical delivery of paclitaxel.
Preclinical studies of TSD-001 have demonstrated solubility and activity against bladder cancer cells in acidic bladder-like environment and improved permeation into bladder without systemic toxicity. LIPAC is pursuing a 505(b)2 approval for TSD-001 and enrolling patients in April 2018 for a Phase 1/2a trial of TSD-001. Part 1 of the study will establish highest tolerable dose and finish second half of 2018. Part 2 is designed to establish human proof of concept as evidenced through patient responder rates in a marker lesion study with data read-out expected in 2019.
If approved, TSD-001 could be the first chemotherapy to be approved for intravesical use in NMIBC in over 20 years.
Bladder cancer is a common disease affecting 3.4 million people globally with approximately 430,000 new cases every year. In the United States, bladder cancer is the sixth most common type of cancer with more than 500,000 bladder cancer patients and about 75,000 new cases per year.
Bladder cancer is generally separated between non-muscle invasive bladder cancer ("NMIBC") and muscle-invasive bladder cancer ("MIBC"). An overwhelming percentage of 70% to 80% of bladder cancer patients are diagnosed with NMIBC, prior to the tumor advancing from the urothelium (bladder lining) into the detrusor muscle of the bladder wall. Although NMIBC survival rates are high, it also has a high recurrence rate of 31-78%, making it expensive to treat and placing a significant financial burden on the healthcare system and severely impacting patients' quality of life.
Lack of effective treatments
Treatment of non-muscle invasive bladder cancers is based on risk stratification. Most patients are initially treated with a transurethral resection of bladder tumor ("TURBT") followed by a single immediate instillation of intravesical chemotherapy to eliminate any residual tumor cells (mitomycin C is typically used in the United States). Subsequent therapy after the treatment above is based on risk and typically consists of one year intravesical treatments of the live vaccine Bacillus Calmette-Guerin ("BCG").
Unfortunately, mitomycin C and BCG lack efficacy as neither have been formulated or approved by the FDA for this indication. Mitomycin C is deactivated by blood thereby blunting its effectiveness when administered post operatively. BCG is not well tolerated while posing a systemic infection risk. Both products are further hydrophilic and are repelled by the urothelium on the bladder wall resulting in limited drug exposure to tumors and overall low efficacy. Both products have also experienced supply shortages and pricing spikes with a major supplier shutting down BCG production in late 2016.
Given the limitations in the current standard of care, there is an opportunity for new safe and efficacious treatments to reduce recurrence of NMIBC thereby improving patient outcomes and reducing the burden on healthcare systems.