Preliminary Phase 2 Data of Ocera Therapeutics' OCR-002 for the Treatment of Liver Cirrhosis and Upper GI Bleeding Show Potent Ammonia Reduction

BARCELONA, Spain and SAN DIEGO, May 29, 2012 /PRNewswire/ --- Hospital Universitari Vall d'Hebron Research Institute in Barcelona and Ocera Therapeutics, Inc. announced today preliminary data from an open label phase 2 study evaluating the overall effectiveness and safety of OCR-002 (ornithine phenylacetate) for the treatment of cirrhosis of the liver and upper GI bleeding. An interim analysis of the first cohort of patients demonstrated that OCR-002 is well tolerated and provided a rapid and durable ammonia reduction after 36 hours of treatment. The data were presented at the 15th International Symposium for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) in Grenaa, Denmark.

OCR-002 is a novel injectable agent that removes toxic, circulating ammonia from the blood. In patients with severe liver impairment, ammonia and other toxic substances that are normally removed by the liver accumulate in the blood and impair the function of brain cells. By removing circulating ammonia, OCR-002 may treat or prevent hepatic encephalopathy (HE), a neuropsychiatric complication of acute liver failure associated with increased levels of circulating ammonia. Signs of HE include impaired cognition, uncontrolled movements and decreased levels of consciousness leading to coma and even death.

"These early data demonstrate that OCR-002 is well tolerated, rapidly normalizes hyperammonemia and has the potential to prevent the development of hepatic encephalopathy," said Dr. Juan Cordoba of Hospital Universitari Vall d'Hebron and the lead investigator of the study. "Cirrhosis patients that present with acute upper gastrointestinal bleeding have a 30% chance of developing hepatic encephalopathy and require intensive care. A medicine that can quickly remove the toxic ammonia may help prevent or reverse this life-threatening condition, minimize the need for intensive care and shorten hospitalization."

The data presented today from the study of Upper GI bleed in patients with liver cirrhosis (n=10) shows that OCR-002 is well tolerated up to 10g/24h and provides a significant, rapid and durable ammonia reduction to normal levels after 36 hours of treatment.  All patients tolerated study drug well for 5 days. There were no severe toxicities associated with the treatment and no incidence of HE, with patients doing well at the 30 day follow up. A rapid drop in ammonia from 80.01+/-13.44 uM at baseline to 41.95+/-4.99 uM was observed at 36 hours (ANOVA, p<0.05).

The Phase 2 clinical trial is ongoing and will enroll 48 patients with cirrhosis of the liver. The first part of the trial recently completed was an open-label study to confirm the safety and tolerability of OCR-002 seen in earlier clinical trials. The second phase is a double-blind, placebo-controlled study and will measure as the primary endpoint ammonia plasma concentration and improvement in HE as a secondary endpoint.

OCR-002, developed by Ocera Therapeutics, has received Orphan Drug designation in the U.S. and Europe and has fast track status in the U.S. OCR-002 is also being evaluated as a treatment of acute liver failure in the U.S. It is estimated that there are up to 1 million cirrhotic patients in the U.S., of which 150,000-200,000 patients are hospitalized due to complications of encephalopathy costing the healthcare system over $1.2 billion every year.

About OCR-002
Ocera in-licensed OCR-002 (ornithine phenylacetate), an ammonia scavenger designed to rapidly lower systemic hyperammonemia and treat hepatic encephalopathy (HE) in patients with liver cirrhosis and acute liver failure from University College of London. 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 and is patent protected until 2031. OCR-002 is being developed as an injectable for hospitalized patients and as an oral formulation to treat HE in patients with chronic liver cirrhosis. Ocera has completed studies in healthy volunteers and cirrhotic patients and phase 2 studies are ongoing. For more information: www.Clinicaltrials.gov (OCR-002)

About Hepatic Encephalopathy (HE)
HE is an often reversible neuropsychiatric complication observed in patients with 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 may elevate 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. 

SOURCE Ocera Therapeutics, Inc.