On June 29, Intercept Pharmaceuticals announced that it has received a complete new drug application from the US FDA regarding its FXR agonist obeticholic acid (OCA) for fibrosis caused by non-alcoholic steatohepatitis (NASH) Response letter (CRL). The FDA stated in the CRL that based on the data reviewed so far, it believes that the expected benefits of the drug based on alternative histopathology trial endpoints are still uncertain, and the benefits of treatment do not exceed the potential risks, so it does not support accelerated approval of OCA for the treatment of NASH Patients who cause liver fibrosis.

Mark Pruzanski, President and CEO of Intercept, commented on the results: “During the review process, the FDA has never communicated information on accelerating the approval of OCA, and we firmly believe that all data submitted so far meets the requirements of the FDA and clearly Support OCA’s positive profit risk. We regret this CRL. The FDA has gradually increased the complexity of histological endpoints, thus creating a very high barrier to pass. So far, OCA is only in a key three phases. This demand has been met during the study. We plan to meet with the FDA as soon as possible to discuss how to pass the approval plan on the CRL information in the future.”

In the race to grab the first listed NASH drug, Intercept has always been in the leading position and is currently the only company that has obtained positive late-stage trial data. As a potent and specific farnesoid X receptor (FXR) agonist, OCA has previously achieved positive results in a phase 3 clinical trial called REGENERATE. The data showed that moderate to severe NASH who received high doses of OCA Among the patients, one-quarter of the patients’ liver fibrosis symptoms have been significantly improved, and the condition has not deteriorated.

The FDA recommended that Intercept submit additional interim efficacy and safety data from the ongoing REGENERATE study to support OCA’s potential accelerated approval, and pointed out that the long-term results of the study should continue.

Although OCA has previously been approved for another rare liver disease (PBC), the field of NASH is huge. It is estimated that NASH affects millions of people in the United States alone. Previously, investment bank JMP Securities estimated that the peak sales of Intercept drugs could reach billions of dollars. Affected by this bad news, Intercept’s stock price fell nearly 40% on Monday to $47.25 per share. The stock prices of other pharmaceutical companies that also developed NASH have also fallen. Among them, Madrigal fell by about 6%, and Viking, Akero and GenFit fell by about 1%.

Stifel analyst Derek Archila wrote in a report to the client that the refusal was due to treatment-related side effects that occurred in OCA clinical testing, that is, some patients received OCA treatment, the harmful cholesterol in the body increased, which in turn Make them have a higher incidence of cardiovascular risk. Given that many NASH patients are already overweight or suffering from type 2 diabetes, such side effects may arouse the vigilance of regulatory agencies. According to the FDA’s requirements for additional test data, Intercept may have to wait until at least the second half of 2022 to interpret these data. External analysis believes that such a long delay may obliterate part of Intercept’s previous accumulated lead, allowing other competitors including Madrigal Pharmaceuticals and Viking Therapeutics to have a chance to catch up.