Alfasigma’s $800 million buyout of Intercept Pharma two years ago is starting to look like a poor bet, as its only approved product, Ocaliva, is pulled off the market in the US and all trials of the drug are placed on hold.
Intercept said it is voluntarily withdrawing Ocaliva (obeticholic acid from sale as a treatment for the rare liver disease primary biliary cholangitis (PBC) following a request from the FDA, 10 years after it was approved for marketing.
For most of that time, it was the only second-line option for PBC after standard frontline treatment, ursodeoxycholic acid (UDCA), although now there are two other options – Ipsen/Genfit’s Iqirvo (elafibranor) and Gilead Sciences’ Livdelzi (seladelpar) – with others coming through regulatory review, including GSK’s linerixibat.
Intercept, which operates as a wholly owned subsidiary of Italy’s Alfasigma since being acquired in September 2023, only has commercial ownership of Ocaliva in the US after selling off ex-US rights to Advanz Pharma in 2022.
The FDA’s request isn’t unexpected, given that the regulator issued a complete response letter (CRL) for Ocaliva last year that was an attempt to convert its accelerated authorisation into a full approval, based on the results of the COBALT trial.
The study, which was halted early, showed no difference between Ocaliva and placebo on the primary endpoint, a composite of the time to death, liver transplant, end-stage liver disease, or hospitalisation of failing liver function. However, Intercept opted to file on the back of real-world data that it said showed a significant reduction in negative clinical outcomes.
That strategy fell apart when an FDA advisory committee concluded there was little evidence for Ocaliva’s efficacy, as well as concerns about safety, which were elevated when the agency said last December that it had identified additional cases of severe liver injury in people treated with the drug.
Meanwhile, the EU regulator revoked the conditional marketing authorisation for Ocaliva last year on the grounds that its benefits no longer outweighed its risks.
Ocaliva was able to stay on the market after the CRL under the terms of its accelerated authorisation, but with multiple options now available, the FDA has opted for caution on the drug. Intercept has also been developing a fixed-dose combination of obeticholic acid in combination with bezafibrate, which now looks rocky after the FDA clinical hold.
“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,” said Intercept’s US president, Vivek Devaraj.
“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.”
