Full approval on Ocaliva for primary biliary cholangitis delayed
A decision by the FDA had been expected by Oct. 15
The U.S. Food and Drug Administration (FDA) is still reviewing Intercept Pharmaceuticals’ application for full approval of Ocaliva (obeticholic acid) as a second-line treatment for primary biliary cholangitis (PBC).
The decision, originally expected by Oct. 15, has now been delayed to an unknown date, according to a press release from Intercept.
Ocaliva was approved in 2016 under the FDA’s accelerated pathway and is still available in the U.S. for use with ursodeoxycholic acid (UDCA), the first-line treatment for PBC, in patients who don’t respond well to UDCA or on its own in those who can’t tolerate UDCA. Accelerated, or conditional, approval is granted when biomarker data from clinical trials suggest a medication intended to treat a serious disease or fill an unmet medical need may work well. More data from additional studies are needed to confirm a treatment’s safety and efficacy for it to advance to full approval.
The delay follows a meeting with patients and doctors last month where an FDA advisory committee agreed in a vote of 10-1 that available data on Ocaliva are not sufficient to demonstrate its clinical benefit and that the medication doesn’t have a favorable benefit-risk profile. The agency typically follows the committee’s recommendation, but it’s not mandatory.
“We will continue to engage with the FDA regarding our pending application,” Vivek Devaraj, Intercept’s president and chairman in the U.S., said in the release. “We are grateful for the continuous and ongoing support of the PBC community.”
PBC is a form of cholangitis, an inflammation of the bile ducts, which normally transport the digestive fluid bile from the liver to the intestines. The inflammation can damage the bile ducts, letting bile accumulates in the liver and leading to cirrhosis, that is, permanent liver scarring, liver failure, and a higher risk of liver cancer.
How does Ocaliva work in PBC?
Ocaliva contains a modified form of a bile acid, the main component of bile, that activates the farnesoid X receptor in the liver that controls bile acid production. By activating the receptor, Ocaliva limits the production of bile acids in the liver, but increases their flow out of the organ.
The therapy is still available in the U.S. under its accelerated approval status for adults with PBC who either don’t have cirrhosis or have compensated cirrhosis, where the liver still functions, and who don’t have portal hypertension, or high blood pressure in the vein that transports blood from the digestive organs to the liver.
Ocaliva’s conditional approval in the European Union (EU), also granted in 2016, was withdrawn last month following a recommendation by an advisory committee that it be revoked because its clinical benefit no longer outweighed its potential risk.
Advanz Pharma, which holds the rights to Ocaliva outside the U.S., appealed and was able to suspend the decision for an undetermined period, so the medication remains available for now.
Conditional approvals in the U.S. and EU drew on data from the Phase 3 POISE clinical trial (NCT01473524) where Ocaliva was shown to be superior to a placebo at helping PBC patients achieve normal blood levels of two markers of liver damage after a year of treatment.
In its applications for full approval, the company also included data from two confirmatory placebo-controlled Phase 4 clinical studies, COBALT (NCT02308111) and Study 401 (NCT03633227), both of which were terminated early.
The COBALT study failed to show that Ocaliva outperformed a placebo in the matter of the number of patients who died or whose liver disease worsened, but a comparison with real-world data from an external group of untreated patients showed Ocaliva reduced by 61%, a significant amount, the risk of these negative clinical outcomes.
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