The U.S. FDA has identified cases of serious liver injury among patients being treated for primary biliary cholangitis (PBC) with Intercept Pharma’s Ocaliva who did not have cirrhosis of the liver, according to a MedWatch warning posted last week.
Ocaliva, a farnesoid X receptor agonist delivered via oral tablet, was first approved in May 2016 to treat adult PBC patients without cirrhosis or with compensated cirrhosis. PBC is a rare, progressive autoimmune disease that causes bile acid to build up in the liver, resulting in inflammation and scarring, which can lead to cirrhosis, a liver transplant or death. Ocaliva has been shown to improve a certain liver test called ALP in patients with PBC who have not responded well enough to ursodeoxycholic acid.
Shortly after its approval, the FDA warned that patients receiving excessive dosing were at an increased risk of liver injury. Then, in May 2021, the agency communicated the risk of serious liver injury associated with Ocaliva, even if dosed properly, restricting its use in PBC patients with advanced cirrhosis of the liver because of the risk of liver failure.
The newest warning sites safety concerns in patients without cirrhosis. According the the FDA, the agency evaluated liver safety in Ocaliva’s postmarket clinical trial and found that the risk of both liver transplant and death were higher in patients receiving Ocaliva compared with those receiving placebo. Specifically, among patients with a lower risk of progression to liver transplant or death, 7 of 81 who received Ocaliva needed a liver transplant compared to 1 of 68 patients who received placebo.
The FDA recommends that doctors should monitor liver tests frequently in patients being treated with Ocaliva to detect and address worsening liver function early.