We have established a portfolio of de-risked assets addressing multiple potential indications.
* TARA-002 Granted Rare Pediatric Disease designation. OK-432 Granted Orphan Drug Designation by the U.S. FDA, applicable under established comparability.
** Granted Orphan Drug and Fast Track Designations by the U.S. FDA
Bladder cancer is the 6th most common cancer in the United States, with non-muscle invasive bladder cancer (NMIBC) representing approximately 80% of bladder cancer diagnoses. Approximately 65,000 patients are diagnosed with NMIBC in the United States each year. NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle. The current standard of care for High Grade NMIBC includes intravesical Bacillus Calmette-Guerin (BCG), which has been the subject of multiple global supply shortages in the past decade due to the inability to meet demand to treat the large worldwide population of patients with NMIBC.
Subject to the successful completion of select non-clinical studies to characterize local toxicity of intravesical administration of TARA-002 as well as acceptance of a pre-Investigational New Drug (IND) filing, the Company plans to commence a Phase 1 study in 2021 to assess the safety and tolerability of TARA-002 in patients with NMIBC, including patients with carcinoma in situ (CIS), with results expected in 2022. The Phase 2 development program, which Protara plans to commence in 2022, is expected to include NMIBC patients with CIS +/- Ta or T1 papillary tumors and High Grade Ta or T1 papillary tumors without CIS.
Lymphatic malformations (LMs) are rare, congenital malformations of lymphatic vessels resulting in the failure of these structures to connect or drain into the venous system. Most LMs present in the head and neck region and are diagnosed in early childhood during the period of active lymphatic growth, with more than 50% detected at birth and 90% diagnosed before the age of 2 years. The most common morbidities and serious manifestations of the disease include compression of the upper aerodigestive tract, including airway obstruction requiring intubation and possible tracheostomy dependence; intralesional bleeding; impingement on critical structures, including nerves, vessels, lymphatics; recurrent infection, and cosmetic and other functional disabilities.
Protara plans to request a meeting with the FDA Division of Vaccines and Related Products Applications by year end to discuss the regulatory path for TARA-002 in LMs. The Company plans to utilize the robust dataset for OK-432 in LMs to support a Biological License Application (BLA) filing for TARA-002 in LMs. In a randomized, Phase 2 clinical trial of OK-432 in LMs conducted in the U.S., 68% of patients treated with OK-432 (>90% pediatric) in the immediate treatment group (n=91) experienced a complete or substantial response. Long-term control of LMs was favorable, with more than 90% of patients treated with OK-432 having no regrowth over a median follow-up period of approximately three years following treatment.
IV Choline Chloride for IFALD
IV choline chloride is an investigational, intravenous (IV) phospholipid substrate replacement therapy initially in development for patients receiving parenteral nutrition (PN) who have intestinal failure-associated liver disease (IFALD).
Choline is a known important substrate for phospholipids that are critical for healthy liver function. Because PN patients cannot sufficiently absorb adequate levels of choline and no available PN formulations contain sufficient amounts of choline to correct this deficiency, PN patients often experience a prolonged progression to hepatic failure and death, with the only known intervention being a dual small bowel / liver transplant. If approved, IV choline chloride would be the first approved therapy for IFALD. It has been granted Orphan Drug Designations (ODDs) by the FDA for the treatment of IFALD and the prevention of choline deficiency in PN patients.
Protara had an end of Phase 2 meeting with the FDA in late 2018 and received the FDA’s support to advance IV choline chloride into a registration-enabling study for the treatment of IFALD.
Intestinal failure-associated liver disease (IFALD), which occurs in patients dependent on PN support, is characterized by choline deficiency, hepatic steatosis, cholestasis, and rapid progression of liver disease through to hepatic failure and death in the absence of intestine-liver transplant. IFALD carries a relatively poor prognosis, with a 15-34% death rate within 1-4 years. When IFALD presents with symptoms of liver disease in children, mortality is even higher (23–40%).
IFALD is uniquely characterized by the presence of both steatosis (toxic fat accumulation in liver cells) and cholestasis (damage to the biliary system in the liver) in patients who are chronic (greater than six months) PN users. A patient is considered to have IFALD if she/he is dependent on PN for more than six months (e.g., has chronic intestinal failure); has evidence of steatosis, determined by imaging techniques or histologic assessments; has evidence of cholestasis (e.g., elevated alkaline phosphatase (ALP), elevated bilirubin and/or histology); and may have evidence of ongoing, progressive liver injury on the basis of multiple abnormal liver function tests, in conjunction with findings of fibrosis, cirrhosis, and/or end-stage liver disease (ESLD).
Expanded Access Policy
Protara is committed to identifying and advancing transformative therapies for the treatment of cancer and rare diseases with significant unmet needs.
Expanded access, also called compassionate use, makes an investigational product available for treatment outside of clinical trials when no comparable or satisfactory alternative therapy option is available. Protara’s product pipeline contains Choline Chloride. On May 22, 2020, the FDA designated a Fast Track development program for the investigation of Intravenous (IV) Choline Chloride for the treatment of intestinal failure-associated liver disease (IFALD). At this time, it is not logistically feasible for Protara to make IV Choline Chloride available for expanded use. Protara is planning for a registration-enabling study for the treatment of IFALD and will provide more information as soon as it becomes available. Protara will continually assess our current expanded access policy and provide updates to this website. We look forward to collaborating with the FDA and making this important therapy available to patients. Please contact us with any questions at firstname.lastname@example.org.