Obeticholic acid
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| Trade names | Ocaliva |
| AHFS/Drugs.com | ocaliva |
| MedlinePlus | a616033 |
| Routes of administration |
By mouth |
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| Identifiers | |
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| Synonyms | 6α-ethyl-chenodeoxycholic acid; INT-747 |
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| ChEMBL | |
| ECHA InfoCard | 100.238.318 |
| Chemical and physical data | |
| Formula | C26H44O4 |
| Molar mass | 420.62516 g/mol |
| 3D model (JSmol) | |
| Melting point | 108–110 °C (226–230 °F) |
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Obeticholic acid (abbreviated to OCA, trade name Ocaliva), is a semi-synthetic bile acid analogue which has the chemical structure 6α-ethyl-chenodeoxycholic acid. It is used as a drug to treat primary biliary cholangitis, and is undergoing development for several other liver diseases and related disorders. Intercept Pharmaceuticals Inc. hold the worldwide rights to develop OCA outside Japan and China, where it is licensed to Dainippon Sumitomo Pharma.
The natural bile acid, chenodeoxycholic acid, was identified in 1999 as the most active physiological ligand for the farnesoid X receptor (FXR), which is involved in many physiological and pathological processes. A series of alkylated bile acid analogues were designed, studied and patented by Roberto Pellicciari and colleagues at the University of Perugia, with 6α-ethyl-chenodeoxycholic acid emerging as the most highly potent FXR agonist. FXR-dependent processes in liver and intestine were proposed as therapeutic targets in human diseases. Obeticholic acid is the first FXR agonist to be used in human drug studies.
Obeticholic acid is undergoing development in phase 2 and 3 studies for specific liver and gastrointestinal conditions. The United States Food and Drug Administration granted accelerated approval to Ocaliva on May 27, 2016 for the treatment of primary biliary cholangitis. It was approved as an orphan drug based on its reduction in the level of the biomarker alkaline phosphatase as a surrogate endpoint for clinical benefit. It is indicated for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA. Additional studies are being required to prove its clinical benefit.
Primary biliary cholangitis (PBC), also known as primary biliary cirrhosis, is an auto-immune, inflammatory liver disease which produces bile duct injury, fibrosis, cholestasis and eventual cirrhosis. It is much more common in women than men and can cause jaundice, itching (pruritus) and fatigue. Ursodeoxycholic acid therapy is beneficial, but the disease often progresses and may require liver transplantation. Animal studies suggested that treatment with FXR agonists should be beneficial in cholestatic diseases such as PBC. OCA at doses between 10 mg and 50 mg was shown to provide significant biochemical benefit, but pruritus was more frequent with higher doses. The results of a randomized, double-blind phase 3 study of OCA, 5 mg or 10 mg, compared to placebo (POISE) were presented in April 2014, and showed that the drug met the trial's primary endpoint of a significant reduction in serum alkaline phosphatase, a biomarker predictive of disease progression, liver transplantation or death.
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