Ocera in-licensed OCR-002 (ornithine phenylacetate) from University College London Business in December 2008. OCR-002 is an ammonia scavenger designed to rapidly lower abnormally elevated systemic ammonia level (hyperammonemia) and treat hepatic encephalopathy (HE) in patients with liver cirrhosis and acute liver failure.
In January 2014, Ocera commenced enrollment in a Phase 2b placebo-controlled, randomized, double-blind trial, "STOP-HE", designed to evaluate the safety, pharmacokinetics and efficacy of intravenously-administered OCR-002 in resolving neurocognitive symptoms of acute HE in hospitalized patients with elevated ammonia.
HE is a reversible neuropsychiatric abnormality observed in patients in acute liver failure or chronic liver cirrhosis in whom the metabolic conversion of ammonia to urea in the liver fails. With severe liver impairment, toxic substances that are normally removed by the liver, such as ammonia, accumulate in the blood. Elevated ammonia levels can impair the function of brain cells, cause cerebral edema and even elevated intracranial pressure. Signs and symptoms of HE include impaired cognition, confusion, and a decreased level of consciousness which can progress to coma and ultimately death. Patients are currently treated with agents that target ammonia production in the gut, such as polydisaccharides and antibiotics.
OCR-002, through its novel mechanism of action, directly lowers circulating blood levels of ammonia by enabling alternate metabolic pathways in the muscle and kidney in patients with liver failure.
In addition to the Company's STOP-HE Phase 2b study, OCR-002 is being evaluated in two investigator-sponsored Phase 2a clinical trials. In March 2015, preliminary topline results were announced from a study in Spain evaluating the effect of OCR-002 on ammonia levels in patients with cirrhosis and upper gastrointestinal bleeing. Enrollment continues in a pilot, open label, dose-ranging study, sponsored by the NIH, to assess the safety and pharmacokinetics of OCR-002 in patients with HE due to acute liver failure or injury.
OCR-002 is in development as both an injectable formulation which is well suited for the hospitalized population with acute HE, and as an oral formulation to provide a chronic use option to maintain remission of HE in patients with liver cirrhosis.
OCR-002 has received Orphan Drug designation in both the U.S. and Europe and has been granted fast track status by the U.S. Food and Drug Administration.