Ocera in-licensed OCR-002 (ornithine phenylacetate) from University College London. OCR-002 is an ammonia scavenger designed to rapidly lower abnormally elevated systemic ammonia levels (hyperammonemia) and treat hepatic encephalopathy (HE) in patients with liver cirrhosis and acute liver failure.
With severe liver impairment, toxic substances that are normally removed by the liver, such as ammonia, accumulate in the blood. Elevated ammonia levels can cause swelling of the brain. 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 laxatives that help eliminate ammonia in the gut and antibiotics that target ammonia production.
Unlike currently approved therapies for HE, OCR-002 is unique in that it directly lowers circulating blood levels of ammonia through pathways that do not require liver function.
OCR-002 is in development as both an intravenous 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.
|Product||Formulation||Indication||Preclinical||Phase 1||Phase 2||Phase 3|
|Cirrhosis and GI
|Acute Liver Failure
*FDA Orphan drug and Fast Track Status **Investigator-sponsored
STOP-HE: Phase 2b Trial in Acute HE
Ocera is currently enrolling patients 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. For more trial-related information, please see our Resources page.
STOP-ALF: Phase 2a Trial for Acute Liver Failure/Injury
In addition to the Company’s STOP-HE Phase 2b study, enrollment continues in a pilot, open label, dose-ranging study sponsored by the NIH, to assess the safety and pharmacokinetics of OCR-002 IV in patients with HE due to acute liver failure or injury. For more trial-related information, please see our Resources page.
Phase 2a Trial in Cirrhosis and Upper GI Bleed
In February 2015, an investigator-sponsored Phase 2a study of OCR-002 IV was completed. Part A, designed as an open-label safety and tolerability study in patients with cirrhosis and upper gastrointestinal (GI) bleeding, demonstrated rapid ammonia lowering in 24 hours in the active cohort. Part B, a placebo-controlled study in patients with decompensated cirrhosis showed rapid reduction in the OCR-002 arm in the first 12-24 hours and a statistically significant difference in urinary excretion of ammonia.
Phase 1 Trial for Chronic HE
Ocera completed a pilot Phase 1 study of the oral formulation of OCR-002 in healthy volunteers in November 2015. Further formulation optimization to enhance controlled delivery of the drug under various conditions is underway.