Obeticholic acid (OCA) — a second-line therapy for primary biliary cholangitis (PBC) withdrawn from the U.S. market last year — was found to be safe and effective for as long as six years, according to a long-term study published in the journal Alimentary Pharmacology & Therapeutics.
The findings come from the five-year open-label extension of the phase 3 POISE trial, the same study behind obeticholic acid’s U.S. approval in 2016. Researchers followed 193 adults (most of them women) with PBC, who were started on OCA 5 mg daily for at least three months, with the option to increase the dose thereafter.
Patients took obeticholic acid daily for a median of about 5.3 years. Their liver blood tests improved and remained that way: 63% met the trial’s primary endpoint at month 72, a combined measure based on alkaline phosphatase and bilirubin, two markers of liver health. Liver stiffness, a sign of scarring measured with a noninvasive scan, held steady throughout the study; this suggests the drug helped keep fibrosis from worsening.
The most common side effect was itching, reported in 70% of patients but mostly mild. Serious liver-related problems were uncommon, affecting about 3%, and two deaths during the study were judged unrelated to the drug. Overall, obeticholic acid “was generally well tolerated with a relatively low discontinuation rate,” the authors wrote.
OCA is a modified form of a bile acid the body makes naturally. It works by switching on a protein in the liver and gut called the farnesoid X receptor (FXR), which acts as a master control for bile acids — helping the body handle them more safely, easing inflammation and possibly slowing the liver scarring seen in PBC.
PBC treatment usually begins with ursodeoxycholic acid (UDCA), a bile acid that improves bile flow and can slow the disease’s progression. However, about 40% of patients do not respond adequately, and 3% to 5% cannot tolerate UDCA. For those cases, obeticholic acid was approved in 2016 as a second-line option under the U.S. Food and Drug Administration’s accelerated approval program, a faster route to market that still requires a follow-up trial to confirm the drug’s benefit.
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That confirmatory trial later identified cases of serious liver injury in some patients taking OCA, even in people without liver cirrhosis, which is listed as a contraindication for therapy with OCA. The European Union revoked the drug’s authorization in 2024, and in September 2025 its manufacturer voluntarily withdrew OCA from the U.S. market. It remains available as a second-line PBC therapy in some countries, including the United Kingdom, Canada and Australia.
