Zydus' Saroglitazar Shows Promising Phase 2b Results in MASH Patients

The results from the randomized, double-blind, placebo-controlled EVIDENCES X trial will be presented as a late-breaking oral presentation at The Liver Meeting 2026, the annual meeting of the American Association for the Study of Liver Diseases (AASLD).

The presentation, titled “Saroglitazar Magnesium Achieves Resolution of Steatohepatitis Without Worsening Fibrosis in Patients with MASH: Results of a Randomized, Placebo-Controlled Phase 2b Trial (EVIDENCES X)”, will be delivered by Naga Chalasani, MD, FAASLD, David W. Crabb Professor of Gastroenterology and Hepatology and Co-Editor-in-Chief of Hepatology.

The 52-week study evaluated the efficacy and safety of once-daily saroglitazar magnesium at doses of 2 mg and 4 mg, compared with placebo, in 189 adults with biopsy-confirmed MASH and stage F2–F3 liver fibrosis. The trial was conducted at clinical sites in Argentina, Turkey and the United States.

The primary endpoint was the resolution of steatohepatitis without worsening of liver fibrosis.

According to the primary analysis, 39.1% of patients receiving saroglitazar magnesium 4 mg achieved the primary endpoint, compared with 32.4% of those receiving the 2 mg dose and 13.7% of patients in the placebo group.

The treatment differences compared with placebo were 24.9 percentage points for the 4 mg dose (95% CI: 9.5–40.3; P=0.002) and 16.5 percentage points for the 2 mg dose (95% CI: 1.3–31.6; P=0.033).

The study also assessed improvement in liver fibrosis by at least one stage without worsening of the NAFLD Activity Score (NAS), a secondary endpoint. This improvement was observed in 34.8% of patients receiving the 4 mg dose, compared with 24.6% in the placebo group and 22.8% in the 2 mg group. However, the difference between the 4 mg and placebo groups did not reach statistical significance.

In addition, the 4 mg dose demonstrated favourable improvements in several non-invasive measures of liver fibrosis compared with placebo. These included Pro-C3, APRI, FIB-4 and ADAPT scores.

Saroglitazar was generally well tolerated during the trial, with no significant weight gain or signal of drug-induced liver injury reported.

Commenting on the findings, Naga Chalasani said that many people with MASH and liver fibrosis also have type 2 diabetes or obesity, highlighting the need for treatment options that address both liver disease and the underlying metabolic dysfunction.

He added that the Phase 2b trial showed a higher proportion of patients achieving resolution of steatohepatitis without worsening fibrosis with saroglitazar than with placebo, alongside improvements in lipid and glycaemic parameters. The findings support further evaluation of saroglitazar in larger, longer-term clinical studies.

Zydus Therapeutics is continuing to evaluate saroglitazar as a potential treatment for adults with MASH and liver fibrosis. Saroglitazar remains an investigational treatment for MASH, and its safety and efficacy for this indication have not been established.

The trial analyses were based on the intention-to-treat population, used a missing-at-random methodology and were stratified according to baseline diabetes status.

EVIDENCES X (NCT05011305) is a multicentre, randomized, double-blind, placebo-controlled Phase 2b clinical trial evaluating the efficacy and safety of saroglitazar in adults aged 18–75 years with biopsy-confirmed MASH, a NAFLD Activity Score (NAS) of at least 4 and stage F2–F3 liver fibrosis.

A total of 189 participants were randomized in a 1:1:1 ratio to receive saroglitazar magnesium 4 mg (64 participants), saroglitazar magnesium 2 mg (63 participants) or placebo (62 participants), once daily for 52 weeks.

The primary endpoint was resolution of steatohepatitis without worsening of fibrosis.

Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as non-alcoholic steatohepatitis (NASH), is a progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD). It is characterized by fat accumulation in the liver, inflammation and liver cell injury.

The disease can progress to liver fibrosis, cirrhosis and hepatocellular carcinoma, potentially requiring liver transplantation and, in severe cases, resulting in death. MASH represents a significant clinical and economic burden worldwide.

Saroglitazar is a peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist being investigated for the treatment of MASH and primary biliary cholangitis (PBC).

The drug is being studied for its potential to address metabolic dysfunction and liver-related disease processes. It has received Orphan Drug Designation, Fast Track Designation and Priority Review from the US Food and Drug Administration (USFDA) for the treatment of PBC.

Zydus Therapeutics Inc., a wholly owned subsidiary of Zydus Lifesciences Limited, is a clinical-stage biopharmaceutical company focused on developing treatments for rare and serious liver diseases, including PBC and MASH. The company is headquartered in Pennington, New Jersey, US.

Zydus Lifesciences Limited is a global life sciences company engaged in discovering, developing, manufacturing and marketing a broad range of healthcare therapies.

The company employs more than 30,000 people worldwide, including approximately 1,500 scientists working in research and development. Its portfolio includes vaccines, therapeutics, biological products and new chemical entities, with a focus on addressing unmet healthcare needs through innovative healthcare solutions.