NEW YORK--(BUSINESS WIRE)--ArTara Therapeutics, a clinical-stage company developing treatments for rare diseases with significant unmet needs, today announced that it has successfully completed an End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) to discuss study of Intravenous (IV) Choline Chloride substrate replacement for patients with Intestinal Failure Associated Liver Disease (IFALD).
IFALD is a devastating disease that impacts a large number of patients who rely on parenteral nutrition for long-term survival. The etiology of IFALD is considered to be multifactorial with a substantial body of literature implicating choline deficiency as a key cause. 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). Because there are currently no available treatments for IFALD there is often a rapid progression to hepatic failure and death in the absence of a dual intestine-liver transplant. There are roughly 25,000 patients on parenteral nutrition annually in the U.S. and the literature suggests that >15% of those are long-term patients who are at greatest risk for developing IFALD.
Pursuant to the meeting, ArTara is now able to initiate its plan for a single, pivotal Phase 3 study to support a New Drug Application (NDA) for IV Choline Chloride for Injection for the treatment of IFALD. ArTara Therapeutics, in consultation with the FDA, reached agreement on pivotal Phase 3 design, dose and co-primary endpoints of improvement in steatosis as measured by MRI-PDFF and improvement in cholestasis as measured by reduction of alkaline phosphatase isoenzyme. The Phase 3 study will further build on the efficacy, safety and tolerability that IV Choline Chloride substrate replacement therapy demonstrated in previous clinical trials in patients with IFALD and choline deficiency.
In a Phase 2 randomized, placebo-controlled study conducted by Dr. Alan Buchman, IV Choline substrate-replacement therapy met its objective of reversal of steatosis and improvement in cholestasis as compared to placebo (Buchman, AL et al. JPEN. 2001:25:260-268).
“For so many of these vulnerable patients who survive long-term on parenteral nutrition, IFALD and transplant is viewed as an inevitability. We are hoping to change this. In both a randomized, placebo-controlled phase 2 study and an open-label pilot study, IV Choline has demonstrated statistically and medically significant results in reversing steatosis and improving cholestasis. When left untreated, these pathologies combine in IFALD patients to cause steady progression to end-stage liver disease. We are looking forward to continuing conversations with the FDA to make this potentially life-saving product available to the thousands of patients who rely on long-term parenteral nutrition and are in need of a treatment for IFALD,” said ArTara Chief Executive Officer, Jesse Shefferman.
About Choline Chloride for Injection, for Intravenous Use
Choline Chloride for Injection is a replacement therapy for patients receiving parenteral nutrition (PN) who are choline deficient. Choline Chloride for Injection has been granted Orphan Drug Designations by the FDA for both the treatment and prevention of Intestinal Failure Associated Liver Disease (IFALD). Choline Chloride for Injection has shown promising results in both reversing steatosis and improving cholestasis in patients dependent on PN and who are also choline deficient. Steatosis and cholestasis are the hallmark pathologies of IFALD. It is estimated that over 80% of patients dependent on PN are unable to adequately synthesize choline, a key precursor to phospholipids critical in the export of triglycerides from the liver, as well as maintenance of healthy bile composition in the biliary system. A significant body of literature suggests that choline deficiency plays a critical role in the frequent development of IFALD in patients dependent on PN.
About ArTara Therapeutics
ArTara is a rare diseases therapeutics company focused on optimizing therapeutics for patients suffering from rare diseases where there is a significant unmet need. Our initial focus is on rare gastrointestinal, metabolic, circulatory and neurological disorders.