In the wake of an unfavorable advisory committee meeting in September, Intercept Pharmaceuticals’ bid to win full approval for its liver disease drug Ocaliva has come up short.
Intercept on Tuesday revealed that it received a complete response letter from the FDA, dashing the company’s hopes of turning Ocaliva’s accelerated green light into a traditional approval for the rare autoimmune disease primary biliary cholangitis (PBC).
The silver lining for the New Jersey-based drugmaker is that Ocaliva will remain available for certain PBC patients in the U.S. under the accelerated nod it received back in 2016, Intercept explained in a release.
PBC, which is most common in women over the age of 40, is marked by the buildup of bile acid in the liver, causing inflammation and scarring that, if left untreated, can lead to cirrhosis, a liver transplant or death.
The FDA continues to weigh safety data from the company’s post-marketing 747-302 study plus other safety information, Intercept said.
The FDA originally planned to reach its verdict on Ocaliva’s approval prospects by Oct. 15, though Intercept announced last month that the agency’s decision had been delayed.
While this certainly wasn’t the outcome Intercept had hoped for, the company intends to work closely with the FDA on next steps for its drug, including additional evidence generation, a spokesperson explained over email.
“We believe in the totality of the evidence supporting Ocaliva for the treatment of appropriate PBC patients,” Intercept’s spokesperson added.
As for what Intercept’s strategy might look like going forward, the company in September proposed a new real-world evidence trial to assess Ocaliva’s long-term impact.
“Beyond this, we will continue to discuss other potential evidence generation with FDA,” the spokesperson said.
The FDA’s rejection doesn’t come as much of a surprise given Ocaliva’s lukewarm reception at a September meeting of the FDA’s Gastrointestinal Drug Advisory Committee, during which a panel of outside experts nearly unanimously voted against Intercept’s request for a full approval of its farnesoid X receptor agonist.
During the meeting, 13 of the FDA’s outside experts said Intercept’s data didn’t adequately prove Ocaliva’s clinical benefit, while just one panelist voted in favor of the drug.
On a second voting question around Ocaliva’s overall risk-benefit profile as a second-line PBC treatment, 10 panelists voted against the drug, one voted for it and three of the experts abstained.
The experts utilized data from two Intercept post-marketing trials—the placebo-controlled 747-302 trial and the observational cohort trial 747-405—to inform their votes.
In briefing documents released ahead of the meeting, the FDA noted that the 747-302 study failed to demonstrate a statistically significant benefit for Ocaliva in PBC and put patients at greater risk of needing a liver transplant or death.
As for 747-405, the FDA argued that the study “[did] not meet regulatory standards for an adequate and well-controlled clinical investigation.”
“We are disappointed in the outcome of today’s Advisory Committee meeting and believe the vote does not accurately recognize the clinical benefit of Ocaliva as an important second-line therapy for patients living with PBC,” Paul Nitschmann, M.D., Intercept’s senior vice president of regulatory affairs, said at the time.
Aside from Ocaliva, patients recently gained two more treatment options thanks to back-to-back approvals for a pair of new PBC drugs this summer. In June, Ipsen and Genfit’s peroxisome proliferator-activated receptor agonist Iqirvo won an accelerated nod from the FDA. Then, in August, Gilead Sciences scored a green light for its own PBC med, Livdelzi, marking the California drugmaker’s first inflammatory drug launch.
Ocaliva has also faced scrutiny from regulators in Europe, where the drug is marketed by U.K.-based Advanz Pharma under a 2022 licensing agreement.
In early September, the European Commission (EC) sought to revoke Ocaliva’s conditional marketing nod in PBC. Fortunately for Intercept and Advanz, the General Court of the European Union temporarily suspended the EC’s decision, allowing Ocaliva to remain on the market for existing PBC patients in EU member states plus Iceland, Liechtenstein and Norway.