FDA issues complete response letter for obeticholic acid for fibrosis due to NASH

The FDA issued a complete response letter for the new drug application for obeticholic acid for treatment of fibrosis due to nonalcoholic steatohepatitis, according to a press release from Intercept Pharmaceutical Inc.

“Today represents a setback first and foremost for NASH patients with advanced fibrosis who have bene waiting far too long for a therapy to treat their disease,” Mark Pruzanski, MD, president and CEO of Intercept, said during a conference call. “It has been an extraordinarily challenging program to get to this point and we believe that we have convincing data that should support the initial approval of the drug to get it to patients. We will move expeditiously to get approval and get it to patients in need.”

According to the release, the FDA determined that the benefit of obeticholic acid (OCA) based on surrogate histopathologic endpoint remains uncertain and did not outweigh potential risks sufficiently to support accelerated approval of the treatment for patients with fibrosis due to NASH. The FDA recommended the company submit additional analysis on efficacy and safety data on OCA from the Randomized Global Phase 3 Study to Evaluate the Impact on NASH With Fibrosis of Obeticholic Acid Treatment (REGENERATE ) trial to support accelerated approval. Additionally, the FDA said the long-term outcomes phase of the study should be continued.

The release noted the NDA for OCA was based on data from 35 clinical trials and over 1,700 patients with NASH who were treated with OCA.

“At no point during the review did the FDA communicate that OCA was not approvable on an accelerated basis, and we strongly believe that the totality of data submitted to date both meet the requirements of the Agency’s own guidance and clearly support the positive benefit-risk profile of OCA,” Pruzanski said in the release. “We are disappointed to see the determination the Agency has reached based on an apparently incomplete review, and without having provided medical experts and patients the opportunity to be heard at the anticipated [advisory committee meeting] on the merits of OCA, which is a designated breakthrough therapy. The FDA has progressively increased the complexity of the histologic endpoints, creating a very high bar that only OCA has so far met in a pivotal phase 3 study. On behalf of the hepatology community, we are very concerned that the Agency’s apparently still evolving expectations will make it exceedingly challenging to bring innovative therapies to NASH patients with high unmet medical need. We plan to meet as soon as possible with the FDA to review the [complete letter response] and discuss options for an efficient path forward to approval.”