Indian regulators clear world's first NASH drug with expanded label for Zydus Cadila's saroglitazar

Zydus Cadila announced Thursday that the Drug Controller General of India (DCGI) has approved its marketing application for saroglitazar to treat patients with non-cirrhotic non-alcoholic steatohepatitis (NASH). According to the company, the dual PPAR agonist, which is already cleared for type 2 diabetes, dyslipidaemia and hypertriglyceridaemia, becomes the first drug anywhere in the world to be approved as a treatment for non-cirrhotic NASH.

The filing was backed by data from the Phase III EVIDENCES II trial comparing saroglitazar versus placebo in terms of histological improvement of NASH using liver biopsy at the end of 52 weeks. Zydus Cadila said that in the study, which enrolled Indian patients, saroglitazar met the primary and secondary endpoints, demonstrating a significant reduction in liver fat, liver enzymes and disease activity. 

The company said that the mid-stage EVIDENCES IV trial of saroglitazar involving US patients with NASH also achieved its primary and secondary goals, with findings having been presented at the American Association for Study of Liver Diseases (AASLD) annual meeting last year. Further, it noted that data from the Phase II EVIDENCES I study has shown that saroglitazar was associated with improvement in liver enzymes and lipids in patients with non-alcoholic fatty liver disease (NAFLD). Sharvil Patel, managing director at Zydus Cadila, said the drugmaker is planning to initiate a Phase III trial in the US in the next two quarters. 

Zydus Cadila is also conducting the EVIDENCES III and EVIDENCES V trials. The first of these is testing saroglitazar versus placebo among NAFLD patients in terms of change in liver fat content as measured by magnetic resonance imaging (MRI), while the second will evaluate change in liver fat in NASH patients over a period of 18 months via MRI-derived proton density-fat fraction, as well as liver biopsy-driven endpoints. 

Patel indicated that he is open to the idea of partnering or out-licensing the drug in markets where the company has limited presence. "Globally, the market potential for NASH treatment is estimated to be around $35 billion to $40 billion…we are looking to have a piece of that pie," he added. 

Last month, NGM Biopharmaceuticals reported Phase II results showing that aldafermin, an engineered variant of the hormone FGF19, significantly reduced absolute liver fat content versus placebo in patients with NASH (for related analysis, see ViewPoints: NGM's interim Phase II look in NASH fails to engender confidence). 

Meanwhile, Intercept Pharmaceuticals submitted a filing with the FDA last year seeking approval for obeticholic acid in patients with fibrosis due to NASH. The application, which is backed by data from the Phase III REGENERATE study, is being assessed by US regulators under a priority review and has a target action date of June 26

Fore related analysis, see ViewPoints: From the clouds – Zydus Cadila’s saroglitazar wins NASH race.

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