FDA still sceptical about Intercept’s NASH drug

Intercept Pharma’s hope that its OCA candidate could become the first FDA-approved drug to treat non-alcoholic steatohepatitis (NASH) is starting to look decidedly faint.

An FDA advisory committee is due to look at the data for OCA (obeticholic acid) for the treatment of NASH-related pre-cirrhotic liver fibrosis on Friday, and the regulator has taken a dim view of the drug in a briefing document published ahead of the meeting.

Overall, the reviewer pointed to “modest” efficacy for the drug – noting that it hit only one of two primary endpoints in the pivotal REGENERATE trial filed in the dossier – that had to be balanced against the risk of side effects including liver damage, cholecystitis and bile duct stones, severe itching, and acute kidney injury.

The document concluded that there are “substantial risks” of adverse events and suggested that the FDA “cannot justify OCA use in NASH subjects with stage 2 or 3 fibrosis.”

This is Intercept’s second attempt at getting OCA over the line for a NASH indication, after its first marketing application was rejected by the FDA in 2020. The agency asked for longer-term efficacy and safety data from REGENERATE.

Intercept tweaked the protocol of the study and reported new results in 2022, saying the new data showed a “strong and confirmed antifibrotic effect” in this patient setting.

The FDA clearly does not believe that is the case and, if the members of its Gastrointestinal Drugs Advisory Committee (GIDAC) agree, Intercept could be looking at a second rejection for OCA in NASH. Shares in the company lost nearly a quarter of their value after the document emerged, before staging a partial recovery to close down 13%.

It’s still possible that experts opt to back the drug – for example, on the basis that clinicians dealing with NASH patients are often highly skilled at managing complications of the disease – but even if that happens there is no guarantee that the FDA will approve it.

In Intercept’s favour is that, in the absence of any approved therapies for NASH, the FDA is asking its advisors for their opinions on whether OCA could be given accelerated approval while the company continues to gather evidence from REGENERATE, which remains ongoing.

A decision is due on 22nd June and, if OCA is turned down again, Intercept could be leapfrogged by other late-stage NASH drugs, such as Madrigal Pharma’s resmetirom, which is due to be filed for approval in the next few weeks.

Intercept already has a revenue stream in place from sales of OCA in a lower-dose formulation, branded as Ocaliva, that is used to treat another form of liver disease called primary biliary cholangitis and made sales of $68 million in the first quarter of this year. However, NASH is a much larger market opportunity.