NEW ORLEANS, May 3 Ocera Therapeutics, Inc. presented today an analysis of the prevalence of neurocognitive impairment in ambulatory cirrhotic patients at Digestive Disease Week (DDW), the annual meeting of the American Gastroenterological Association. The data, which came from the screening period of the ASTUTE Study demonstrated that 54% of the 301 cirrhotic patients screened had neurocognitive impairment. ASTUTE is an ongoing Phase 2b study evaluating the safety and efficacy of AST-120 (spherical carbon adsorbent) in the treatment of mild hepatic encephalopathy (MHE), a reversible condition caused by the failure of the cirrhotic liver to eliminate ammonia from the blood stream. Efficacy and safety data from the study are expected in the summer of 2010.
"There is a high prevalence of neurocognitive impairment in cirrhotic patients, and this data suggest that even the most well compensated cirrhotics are at high risk for MHE," said Dr. Kevin Mullen, Consultant Hepatologist and Professor of Medicine at Case Western Reserve University. "We need to start considering that MHE may be present in all of our cirrhotic patients. It can no longer be ignored."
In this randomized, double-blind, placebo controlled trial the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess otherwise stable cirrhotics for MHE, which was defined in the protocol as an RBANS score below the 10th percentile for their age and educational level. This is a greater level of impairment than that used in Alzheimer's disease research. The mean RBANS score for the eligible subjects was 74, indicating average neurocognitive status below the 5th percentile of normal.
Those who were eligible for the ASTUTE Study did not differ from those who were not eligible across multiple demographic and disease severity characteristics, including age, gender, etiology of underlying liver disease, education level, MELD score, platelet count, bilirubin levels and presence of esophageal varices, demonstrating the importance of clinicians not assuming that patients with less advanced cirrhosis will not have MHE.
"This study demonstrates that a majority of healthy-appearing cirrhotics suffer from clinically significant neurocognitive impairment, of a magnitude that is certain to impact basic activities of daily living," said Dr. Christopher Randolph, Clinical Professor of Neurology, Director, Neuropsychology Service at Loyola University Medical Center and the presenting author of the presentation. "There is clearly a large unmet need for treatment of affected patients, and we look forward to the final ASTUTE study results to see what impact AST-120 will have in this population."
About ASTUTE Study
ASTUTE is a randomized, double blind, multicenter study evaluating 148 patients with liver cirrhosis and MHE. The study employed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), a validated instrument developed by Dr. Christopher Randolph of Loyola University in Chicago. RBANS was used to screen cirrhotic patients for evidence of MHE and study eligibility, and found that MHE was present in the majority of patients screened. The study is designed to evaluate the effects of AST-120 compared to placebo on neurocognitive function using a variety of validated instruments. In addition, quality of life and clinical global evaluations as well as safety assessments are being conducted.
AST-120 is a novel proprietary spherical carbon adsorbent with a selective adsorption profile for a variety of unwanted substances and toxins, most importantly ammonia, the primary toxin linked to hepatic encephalopathy in patients with liver cirrhosis. AST-120 also adsorbs other substances, which may be responsible for conditions including Irritable Bowel Syndrome (IBS), and pouchitis. Adsorbed substances include ammonia, indoles (serotonin), histamine, bile acids, advanced glycation endproducts (AGE), and certain bacterial toxins. Ocera licensed the compound from Kureha Corporation (Japan) in 2005. AST-120 has been used chronically by over 360,000 patients and studied in over 3,000 patients worldwide.
About Hepatic Encephalopathy
Hepatic Encephalopathy (HE) is a neuropsychiatric condition in which severe liver disease contributes to an accumulation of toxic substances, including ammonia that impair brain function. HE ranges in severity from mild personality changes to disorientation, delirium, coma and death. It has been reported that over 50% of patients with cirrhosis of the liver who do not have evidence of overt HE will still have neuropsychiatric impairment if tested. This more subtle impairment has been termed MHE, and has been associated with impaired quality of life, job loss and increased risk of motor vehicle accident in these patients. MHE is currently rarely diagnosed by physicians and there are no approved treatments for MHE.
About Ocera Therapeutics, Inc.
Ocera Therapeutics, based in San Diego, California, USA, is a privately held biopharmaceutical company focused on the development and commercialization of proprietary compounds to treat acute and chronic liver diseases and a broad range of gastrointestinal disorders. In addition to AST-120, Ocera is developing OCR-002, an ammonia detoxification agent, for the treatment of hospitalized patients with acute hepatic encephalopathy and acute liver failure. Ocera has raised $62.5 million dollars in venture financing from Domain Associates, Sofinnova Ventures, Thomas, McNerney & Partners, Montagu Newhall and InterWest Partners. Additional information on the company can be found at www.oceratherapeutics.com.
SOURCE Ocera Therapeutics, Inc.