Zydus Reports Positive Phase II(b) Results for Saroglitazar in MASH

EVIDENCES-X Study Meets Its Primary Endpoint

Zydus Lifesciences Limited has reported positive topline results from its completed global Phase II(b) EVIDENCES-X clinical trial evaluating saroglitazar magnesium, also known as saroglitazar Mg, in patients with metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis.

The study successfully met its primary endpoint at Week 52.

The results add new clinical evidence to Zydus' ongoing development program for saroglitazar Mg and its potential role in treating chronic liver diseases.

Study Included 189 Patients

EVIDENCES-X was designed as a prospective, multicenter, randomized, double-blind and placebo-controlled Phase II(b) study.

A total of 189 patients were enrolled in the trial and randomly assigned in a 1:1:1 ratio to receive one of three treatments.

Participants received either saroglitazar 2 mg, saroglitazar 4 mg or placebo.

Treatment continued for 52 weeks, allowing researchers to assess changes in liver disease and fibrosis over a longer period.

The global study was conducted across the United States, Turkey and Argentina.

Primary Endpoint Was Achieved

The main goal of the EVIDENCES-X study was to determine whether treatment could lead to resolution of steatohepatitis without worsening of liver fibrosis at Week 52.

Saroglitazar achieved the primary endpoint, with a treatment difference of 26.5%.

This means the treatment group showed a meaningful difference compared with placebo in the proportion of patients achieving the defined histological improvement without worsening of fibrosis.

The company said the result supports continued development of saroglitazar Mg in MASH.

Other Liver Disease Measures Also Improved

The study also produced encouraging findings across several secondary and exploratory measures.

Researchers evaluated different aspects of liver disease, including liver histology, steatosis, inflammation and ballooning.

The findings showed improvements across these parameters, adding to the overall clinical picture from the study.

Zydus has not yet released the complete detailed dataset from EVIDENCES-X. The company plans to present the full results at an upcoming Liver Congress and submit the data for publication in a peer-reviewed medical journal.

Experts Led the Global Study

The EVIDENCES-X trial was led by Prof. Naga Chalasani, M.D., interim chair of the Department of Medicine at Indiana University School of Medicine, and Professor Arun J. Sanyal, M.D., of the Division of Gastroenterology at Virginia Commonwealth University.

They served as co-Principal Investigators for the global study.

The involvement of experienced researchers in liver disease reflects the focus of the trial on evaluating saroglitazar Mg in patients with MASH and fibrosis.

Why MASH Is a Major Health Concern

MASH is part of a broader group of liver conditions associated with metabolic dysfunction.

Metabolic dysfunction-associated steatotic liver disease, or MASLD, affects an estimated 25% of adults worldwide.

MASH is a more serious form of the disease in which fat accumulation in the liver is accompanied by inflammation and liver cell injury.

It can become progressively worse over time.

In some patients, MASH can lead to advanced fibrosis, cirrhosis, liver failure and liver cancer. Severe disease can ultimately result in death.

Because of this progression, there is a significant need for treatments that can address both liver inflammation and the underlying metabolic problems associated with the disease.

What Happens to the Liver in MASH?

MASH develops when excess fat builds up in the liver along with inflammation and hepatocellular injury.

As the disease continues, the liver may begin forming scar tissue, known as fibrosis.

If fibrosis becomes advanced, normal liver structure and function can be seriously affected.

For patients, this means a condition that may initially have few obvious symptoms can eventually become a serious chronic disease.

This is one reason clinical trials such as EVIDENCES-X measure not only liver fat but also inflammation, ballooning and fibrosis.

Saroglitazar Mg Has Already Been Approved in India

Saroglitazar Mg is not a completely new compound.

In India, it was approved by the Drug Controller General of India in 2020 for the treatment of MASH and MASLD.

Zydus has been studying the medicine further in clinical trials to build evidence for its use across different patient populations and markets.

The EVIDENCES-X results add to data generated in earlier Phase II studies evaluating saroglitazar in patients with MASH and MASLD.

The Drug Is Still Investigational in the US and Europe

The regulatory status of saroglitazar Mg is different outside India.

In the United States, saroglitazar Mg remains an investigational compound for MASH and MASLD.

It has not been approved by the U.S. Food and Drug Administration for these conditions.

The medicine has also not been approved by the European Medicines Agency for the treatment of MASH or MASLD.

The positive EVIDENCES-X results could therefore become an important part of Zydus' continued global development strategy, but additional clinical and regulatory steps will be required before any potential approval in these markets.

EVIDENCES-X Builds on Earlier Clinical Research

The Phase II(b) study is part of a broader development program for saroglitazar Mg.

Earlier Phase II studies have evaluated the compound in patients with MASH and MASLD and generated clinical evidence supporting further investigation.

The latest results provide additional information from a larger global study involving patients with MASH and fibrosis.

Zydus said the findings support the ongoing global development program for saroglitazar Mg in chronic liver diseases.

What Zydus Plans to Do Next

The company is preparing to share more detailed findings from EVIDENCES-X at an upcoming Liver Congress.

The complete study results are also expected to be submitted to a peer-reviewed medical journal.

These additional data will provide more information about the treatment effects observed across the different study groups and liver disease measures.

For Zydus, the next stages will focus on advancing the global development of saroglitazar Mg and continuing to evaluate its potential in patients with chronic liver disease.

Zydus' Focus on Chronic Liver Disease

Dr. Sharvil Patel, managing director of Zydus Lifesciences Limited, said the successful completion of the EVIDENCES-X Phase II(b) trial and achievement of its primary endpoint represent an important milestone for the company's MASH development program.

He also said the results reinforce the therapeutic potential of saroglitazar Mg and Zydus' focus on developing treatment options for people living with chronic liver diseases.

The company is continuing to build clinical evidence around saroglitazar Mg as it advances its global development program.

About Zydus Lifesciences

Zydus Lifesciences Limited is a global pharmaceutical company involved in the research, development and commercialization of healthcare products.

The company is developing medicines across several therapeutic areas and is continuing to expand its research programs in chronic diseases.

Its saroglitazar Mg program is focused on metabolic and liver diseases, including MASH and MASLD, with clinical development continuing in international markets.