Compilation 丨Fan Dongdong
On June 29, Intercept Pharmaceuticals announced that it had received a complete response letter (CRL) from the U.S. FDA regarding its FXR agonist Obeticholic acid (OCA) for fibrosis caused by non-alcoholic steatohepatitis (NASH). The FDA said in the CRL that based on the data reviewed so far, the expected benefits of the drug based on the endpoints of alternative histopathology trials remain uncertain, and that the treatment benefits do not outweigh the potential risks, so it does not support accelerated approval of OCA for the treatment of nash-induced patients with liver fibrosis.
Mark Pruzanski, President and CEO of Intercept, said of the results: "During the review process, the FDA never communicated a message to accelerate approval of the OCA, and we strongly believe that all data submitted to date meet the requirements of FDA regulations and explicitly support the positive benefit risks of OCA." We regret this CRL. The FDA has gradually increased the complexity of the histological endpoint, creating a very high barrier to entry, which so far the OCA has only met in one critical Phase 3 study. We plan to meet with the FDA as soon as possible to discuss how to pass approved options in the future on the CRL's message. ”
Intercept has been in the lead in the race to grab the first NASH drug to hit the market and is currently the only company to have access to data for aggressive late-stage trials. As a potent, specific farnixol X receptor (FXR) agonist, OCA previously achieved positive results in a Phase 3 clinical trial called RESTORE, which showed that one in four patients receiving high doses of OCA with moderate to severe NASH had significant improvements in symptoms of liver tissue fibrosis and no worsening of the condition.
The FDA recommended that Intercept submit additional interim analytical efficacy and safety data from the ongoing REGENERATE study to support OCA's potentially accelerated approval, noting that the long-term results of the study should continue.
While OCA has previously been approved for another rare liver disease (PBC), the NASH field has a huge space. 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 the bearish news, Intercept's stock price fell nearly 40% on Monday to $47.25 per share. Shares of other drugmakers that also developED NASH also fell, with Madrigal down about 6 percent and Viking, Akero and GenFit down about 1 percent each.
Stifel analyst Derek Archila wrote in a report to clients that the rejection was due to the treatment-related side effects that occurred in the OCA clinical test, that is, some patients had increased harmful cholesterol in the body after receiving OCA treatment, which in turn made their cardiovascular risk more frequent. Given that many NASH patients are already overweight or have type 2 diabetes, such side effects could raise the alarm of regulators. Depending on the FDA's requirements for additional trial data, Intercept may not interpret the data until at least the second half of 2022. Outside analysts believe that such a long delay may erase some of the lead that Intercept has accumulated before, giving other competitors, including Madrigal Pharmaceuticals and Viking Therapeutics, a chance to catch up.
References:
1、Intercept's NASH drug faces its biggest delay yet
2、Intercept's NASH hopeful spurned by FDA, raising questions for other companies in the race