Millions of people with a progressive liver condition will have to wait longer for a treatment for it to become available. The FDA has refused to approve an application for obeticholic acid (OCA) for patients with advanced-stage non-alcoholic steatohepatitis (NASH). Instead, the agency told the compound's owner, Intercept Pharmaceuticals (NASDAQ:ICPT), to try again and come back with more evidence that OCA can safely improve outcomes for people with NASH-related liver fibrosis.
Complete response letter
The FDA sent Intercept Pharmaceuticals what's called a complete response letter (CRL) asking for more evidence of the drug's efficacy and safety. This isn't an outright denial, but it does mean the company will need to produce more evidence the treatment's efficacy outweighs its potential safety issues.
In its application, Intercept offered the FDA the results from its Regenerate study, which tested two different dosages of OCA among patients with different stages of NASH. In a nutshell, that study suggests that a dosage high enough to be measurably effective could also be too dangerous.
Patients with stage 2 and 3 fibrosis treated with a high dose of OCA showed improvement in terms of liver tissue stiffness, but their NASH symptoms weren't significantly better. Unfortunately, a majority of patients treated with the effective dosage also reported chronic itching. That might not sound like such a bad trade-off for a treatment that helps with a chronic disease, but itching can be caused by a damaged liver leaking bile acids into the bloodstream, so as a symptom, it must be taken seriously here.
In May, the coronavirus pandemic led the FDA to postpone an independent advisory committee meeting to discuss Intercept's OCA application. Without briefing documents from a publicly held advisory committee meeting, we really don't know what the agency has told the company.
The contents of CRLs -- like most communications with the FDA -- aren't subject to disclosure, so the only side of this story we'll get to hear is Intercept's. The company says it believes it followed the FDA's instructions to the letter and plans to submit an updated application with additional results from the Regenerate study that haven't been reported yet.