PBC treatment Ocaliva leaves U.S. market amid safety concerns
FDA puts US clinical trials on hold
Intercept Pharmaceuticals has voluntarily withdrawn Ocaliva (obeticholic acid), an oral therapy used to treat certain adults with primary biliary cholangitis (PBC), from the U.S. market following a request from the U.S. Food and Drug Administration (FDA).
The FDA has also placed a clinical hold on all Intercept-sponsored Ocaliva clinical trials underway in the U.S., the company said.
The decisions come amid emerging safety concerns. The FDA said late last year that it had identified a risk of serious liver injury in PBC patients who used Ocaliva, including those who did not have existing cirrhosis (advanced liver scarring and damage) when they started the therapy.
Intercept said patients currently prescribed Ocaliva should consult with their healthcare providers. The company will provide additional information to support physicians and patients during the transition process.
“We continue to believe the totality of clinical and real-world evidence supports Ocaliva’s use for appropriate patients, and we are proud of the contribution Ocaliva has made in advancing care for people living with PBC,” Vivek Devaraj, Intercept’s U.S. president, said in a company press release.
Treatment was conditionally approved
Ocaliva was conditionally approved by regulators in the U.S. and European Union (EU) in 2016 as a second-line PBC treatment for adults who had an inadequate response to, or could not tolerate, first-line ursodeoxycholic acid (UDCA).
Conditional approvals allow a therapy to be marketed based on early evidence that it is likely safe and effective. Earning full approval then requires further data demonstrating that the treatment is of clinical benefit to patients.
U.S. regulators rejected Intercept’s application seeking conversion to a full approval last year, citing insufficient evidence to support a favorable benefit-risk profile.
Regulators in the EU, where Advanz Pharma sold Ocaliva, revoked the treatment’s conditional marketing authorization last year.
“While our view of Ocaliva’s benefit-risk profile differs from FDA’s, we respect its request and have made this difficult decision to provide clear guidance for patients and prescribers,” Devaraj added, noting that the company “remains committed to serving the needs of patients and physicians.”
PBC is a rare autoimmune condition characterized by chronic cholangitis, or inflammation in the ducts that carry the digestive fluid bile from the liver to the small intestine. Bile can consequently accumulate in the liver, causing severe damage.
Ocaliva is an oral therapy designed to activate the farnesoid X receptor, a protein that regulates bile acid production. The aim is to lower bile acid levels in the liver to prevent damage.
Data from the Phase 3 POISE trial (NCT01473524) showed that Ocaliva was superior to a placebo for normalizing blood biomarkers of liver damage and scarring, supporting its conditional approvals.
After the treatment’s clearance, reports of liver injury began to emerge. In 2021, regulators found that PBC patients with cirrhosis were at a particular risk, subsequently updating the label to restrict Ocaliva’s use in people with advanced cirrhosis.
Additional studies, including the Phase 4 COBALT clinical trial (NCT02308111), were intended to support eventual conversion to full approval.
Trial results showed similar rates of death and serious liver-related events between participants taking Ocaliva and those given a placebo. However, another prespecified analysis showed that Ocaliva reduced those clinical events by 61% relative to real-world data from an external group of untreated adults with PBC.
The FDA, in declining to give full approval, said it was still considering safety data from COBALT and other studies. At the time, Ocaliva was still available to patients under its conditional marketing authorization.
The FDA statement issued in December said that postmarketing data demonstrated that the risk of serious liver injury was also present for patients without cirrhosis treated according to the indications on the prescribing label.
EU regulators revoked the treatment’s conditional approval based on an advisory committee’s recommendation that Ocaliva’s benefits no longer outweighed its risks. Advanz won a temporary suspension of that decision, but ultimately, it went into effect, and Ocaliva was withdrawn from the market.
Healthcare professionals with questions about Ocaliva can contact Intercept Medical Information by email or phone. Patients with questions should speak to their healthcare team and may contact Intercept’s patient support services by phone.
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