Drug/Device PipelinePerspective

FDA Accepts Ocaliva NDA for NASH

The FDA accepted the first new drug application for the treatment of liver fibrosis due to nonalcoholic steatohepatitis; Intercept announced that obeticholic acid, already approved for the treatment of primary biliary cholangitis under the Ocaliva brand, has a PDUFA date of March 26, 2020.

“If approved, OCA would be the first available therapy for patients with fibrosis due to NASH, a condition that is expected to become the leading cause of liver transplant in the U.S. as soon as 2020,” Mark Pruzanski, MD, president and CEO of Intercept, said in a press release issued by the manufacturer. “It is exciting to achieve this critical regulatory milestone that brings us one step closer to our goal of delivering the first approved therapeutic to those living with this devastating disease. From OCA’s prior designation as a Breakthrough Therapy to the grant of priority review today, our work with the FDA continues to set an important precedent for the field, and we look forward to working with the agency over the coming months as they review the first NDA in NASH.”

Obeticholic acid (OCA, Intercept Pharmaceuticals) first received breakthrough designation from the FDA for this treatment in 2015 and interim results from the phase 3 REGENERATE study were presented at the International Liver Congress in April 2019 in what the presenter called a ‘watershed moment.’

The REGENERATE study, which focused on prespecified endpoints of NASH treatment with OCA, included 931 participants with biopsy-confirmed NASH and stage F2 or F3 fibrosis. Investigators randomly assigned patients to receive either placebo (n = 311), OCA 10 mg (n = 312) or OCA 25 mg (n = 308).

In looking at the primary endpoints of either fibrosis improvement (1 stage) with no worsening of NASH or NASH resolution with no worsening of liver fibrosis on liver biopsy, there was dose-dependent response. Daily OCA of 25 mg met the primary endpoint of fibrosis improvement without worsening of NASH in 23.1% of patients (P = .0002 vs. placebo). The 10-mg group showed a 17.6% improvement (P = .04 vs. placebo).

Experts have speculated that this will be the first approval in the NASH treatment paradigm, likely setting the stage for others to come in its wake.

Reference: Intercept Pharmaceuticals

The FDA accepted the first new drug application for the treatment of liver fibrosis due to nonalcoholic steatohepatitis; Intercept announced that obeticholic acid, already approved for the treatment of primary biliary cholangitis under the Ocaliva brand, has a PDUFA date of March 26, 2020.

“If approved, OCA would be the first available therapy for patients with fibrosis due to NASH, a condition that is expected to become the leading cause of liver transplant in the U.S. as soon as 2020,” Mark Pruzanski, MD, president and CEO of Intercept, said in a press release issued by the manufacturer. “It is exciting to achieve this critical regulatory milestone that brings us one step closer to our goal of delivering the first approved therapeutic to those living with this devastating disease. From OCA’s prior designation as a Breakthrough Therapy to the grant of priority review today, our work with the FDA continues to set an important precedent for the field, and we look forward to working with the agency over the coming months as they review the first NDA in NASH.”

Obeticholic acid (OCA, Intercept Pharmaceuticals) first received breakthrough designation from the FDA for this treatment in 2015 and interim results from the phase 3 REGENERATE study were presented at the International Liver Congress in April 2019 in what the presenter called a ‘watershed moment.’

The REGENERATE study, which focused on prespecified endpoints of NASH treatment with OCA, included 931 participants with biopsy-confirmed NASH and stage F2 or F3 fibrosis. Investigators randomly assigned patients to receive either placebo (n = 311), OCA 10 mg (n = 312) or OCA 25 mg (n = 308).

In looking at the primary endpoints of either fibrosis improvement (1 stage) with no worsening of NASH or NASH resolution with no worsening of liver fibrosis on liver biopsy, there was dose-dependent response. Daily OCA of 25 mg met the primary endpoint of fibrosis improvement without worsening of NASH in 23.1% of patients (P = .0002 vs. placebo). The 10-mg group showed a 17.6% improvement (P = .04 vs. placebo).

Experts have speculated that this will be the first approval in the NASH treatment paradigm, likely setting the stage for others to come in its wake.

Reference: Intercept Pharmaceuticals

    Perspective
    Stephen Harrison

    Stephen Harrison

    We should be highly optimistic; with the acceptance of the NDA, we are on an unchartered course in NASH at the precipice of our first FDA-approved treatment for this liver disease. The implications of this are profound.

    Not only do we give hope to our patients with NASH and fibrosis, but we can inform primary care physicians and gastroenterologists that there is an FDA approved treatment for this disease on the horizon. Therefore, the excuse of ‘we aren’t going to look for it because there is no treatment’ is gone.

    This will improve disease awareness to patients and to providers. Additionally, it will give hope to the drug development community that there is a pathway to approval if your drug works.

    As pharma sees a path to drug approval, they will also see the opportunity to build on the success of Intercept. Hence, it will allow us to move forward with combination therapies to further improve the chances of patients benefiting from obeticholic acid and other drugs to come.

    • Stephen Harrison, MD
    • Medical Director
      Pinnacle Clinical Research
      San Antonio, TX

    Disclosures: Harrison reports consulting for Akero, Altimmune, Axcella, Blade Therapeutics, Cirius, CiVi Biopharma, Cymabay, Echosens, Foresite, Galectin, Galmed, Genfit, Genentech, Gilead, Hepion, Hightide, HistoIndex, Innovate, Intercept, Madrigal, Medpace, Metacrine, NGM Bio, Novartis, Novo Nordisk, Perspectum, Poxel, Prometic, Sagimet and Viking.