Zydus Lifesciences initiates phase 4 trial for Saroglitazar Mg in NAFLD

Zydus Lifesciences, an Indian life sciences company, has announced the commencement of Phase IV Real World Data Registry trial “EVIDENCES-XI” for Saroglitazar Magnesium (Mg) in patients with non-alcoholic fatty liver disease (NAFLD) and comorbidities.

This late-stage trial aims to evaluate the efficacy of Saroglitazar Mg in approximately 1,500 male and female NAFLD patients, each with comorbidities such as obesity, type 2 diabetes mellitus, dyslipidemia, or metabolic syndrome.

The Phase IV EVIDENCES-XI trial, with an expected duration of 56 weeks, will focus on measuring the change in liver stiffness using transient elastography from Baseline to Week 52 as the primary endpoint. This comprehensive study holds the potential to generate vital real-world data in NAFLD patients, particularly in Asian populations where such information is scarce.

The resulting data will not only help shape clinical guidelines but also contribute to enhancing the understanding of Saroglitazar Mg’s role in the management of NAFLD.

Prior to this Phase IV trial, Saroglitazar Mg has undergone two well-controlled Phase 3 clinical trials in India, specifically targeting patients with NAFLD and non-alcoholic steatohepatitis (NASH). The initial Phase 3 trial, conducted among biopsy-proven NASH patients, exhibited a significant 28% difference compared to the placebo group in the primary endpoint of NAFLD Activity Score (NAS).

Zydus Lifesciences begins phase 4 trial for Saroglitazar Mg in NAFLD. Photo courtesy of Zydus Cadila.

Furthermore, there was no worsening of fibrosis in a higher proportion of patients. The second Phase III study focused on measuring changes in liver fat content through non-invasive magnetic resonance imaging (MRI) and demonstrated the beneficial effects of Saroglitazar Mg on the primary endpoint in NAFLD patients at week 24.

In the United States, the ongoing ‘EVIDENCES-X’ Phase 2b study of Saroglitazar Mg involves 240 patients with NASH, with a biopsy-driven end-point lasting 72 weeks. Notably, the Phase 2 results of Saroglitazar Mg in patients with NAFLD were published in the “Oct 2021 issue of Hepatology,” while the results of Saroglitazar Mg’s Phase 2 trial in patients with post-transplant NASH were published in the “Clin Gastroenterol Hepatol” journal.

Furthermore, Saroglitazar Mg has also been studied in patients with Primary Biliary Cholangitis (PBC), a rare liver disease, through the EPICS-I and EPICS-II series of trials conducted in the United States and Mexico. The Phase 2 study results for PBC patients have been published in prestigious journals such as the “Journal of Hepatology” and “Gastroenterol Hepatology.”

Currently, a third Phase 2b/3 adaptive trial, known as EPICS-III, is underway in patients with PBC, with multiple sites in the United States and Europe. Saroglitazar Mg has received Fast Track status and Orphan Drug Designation from the US Food and Drug Administration (USFDA) for the treatment of PBC. Additionally, it has obtained Orphan Drug Designation in Europe, which grants it 10 years of market exclusivity upon approval.

The initiation of the Phase IV EVIDENCES-XI trial marks an important milestone in the research and development of Saroglitazar Mg as a potential therapeutic option for patients with NAFLD and related comorbidities. Zydus Lifesciences’ dedication to addressing the unmet healthcare needs of NAFLD and NASH patients showcases its commitment to advancing medical science and improving patient outcomes in liver diseases.

Pankaj R. Patel — Zydus Lifesciences Chairman said: “NAFLD and NASH are serious life-threatening conditions and we have now studied Saroglitazar Mg in over 10 different trials which have been completed and the ongoing EVIDENCES I to X series of clinical trials in patients with NAFLD and NASH across clinical sites in India, Mexico, USA and Europe.

“I’d like to thank all the patients, investigators and study sites that are now participating in our Phase 4 EVIDENCES-XI Real World Evidence trial. We hope that this will be a big leap forward in managing and treating the unmet healthcare needs of NAFLD and NASH.”