Zydus announces positive results from EVIDENCES IV Phase 2 clinical trial of Saroglitazar Magnesium in NAFLD and NASH

Zydus Cadila recently announced that Saroglitazar Magnesium has achieved the primary end-points in the EVIDENCES IV trial in patients with NAFLD and NASH.

Saroglitazar Magnesium is an investigational molecule in USA, undergoing clinical evaluation for treatment of liver diseases like NAFLD with polycystic ovary syndrome (PCOS), Nonalcoholic'Steatohepatitis (NASH) and Primary Biliary Cholangitis (PBC). Nonclinical studies have demonstrated that Saroglitazar, because of its unique mechanism of engaging PPAR alpha and PPAR gamma, favorably affects all components of NASH including steatosis, ballooning, inflammation and fibrosis.

The EVIDENCES IV NASH trial was a randomized, double-blind, placebo-controlled study that enrolled 106 patients with Non Alcoholic Fatty Liver Disease (NAFLD), including Non-Alcoholic Steatohepatitis (NASH) across 20 clinical sites in the United States of America. Patients were randomly assigned in a ratio of 1:1:1:1 to receive Saroglitazar Magnesium 1mg or 2 mg or 4 mg or matching placebo once daily in the morning before breakfast for 16 Weeks.

Prof. Naga P. Chalasani, MD, Associate Dean for Clinical Research and Director, Division of Gastroenterology & Hepatology, Indiana University School of Medicine, USA, an authority in the fields of NAFLD and drug induced liver injury (DILI), was the lead Principal Investigator of the EVIDENCES IV trial. Prof. Chalasani stated “Saroglitazar 4 mg significantly improved liver biochemistries, hepatic steatosis, dyslipidemia, and insulin resistance, with no weight gain or fluid retention. These results are quite encouraging as there is a significant unmet need for patients with NAFLD and NASH for a drug that improves not just the liver disease, but important comorbidities such as insulin resistance and dyslipidemia.”

Speaking on the development, Mr. Pankaj R. Patel, Chairman, Zydus Group said, “We are happy with the positive results that Saroglitazar Magnesium has shown in the EVIDENCES IV trial. We look forward to presenting the detailed data in upcoming scientific conferences and publishing the study findings in peer-reviewed scientific journals.”

The primary endpoint of the study was percentage change from baseline in serum ALT levels at Week 16 in the Saroglitazar Magnesium groups as compared to the placebo group. There was a statistically significant reduction in mean ALT from baseline to week 16 observed with all doses of Saroglitazar as compared to placebo.

A statistically significant reduction in hepatic fat content from baseline was observed in patients treated with Saroglitazar Magnesium as compared to placebo following 16 weeks of treatment as measured by MRI-PDFF. The secondary endpoints of the trial also included measurements of other liver enzymes, Insulin resistance, Liver fibrosis, BMI, Waist circumference, MRI-derived measures of total liver fat index, Lipid and lipoprotein levels, and pharmacokinetic parameters.

This study is one of several EVIDENCES trials conducted to assess the effect of Saroglitazar Magnesium in various populations with NAFLD, including patients with NASH.

NASH is a progressive disease of the liver. Starting with fat accumulation in liver, this condition can progress to cirrhosis and liver failure. NASH ranks as one of the major causes of cirrhosis in America, behind hepatitis C and alcoholic liver disease. Liver transplantation is the only option for managing advanced cirrhosis with liver failure. There are currently no treatments approved by the U.S. Food and Drug Administration (USFDA) for treatment of NASH.