Saroglitazar Resolves MASH Without Fibrosis Worsening: EVIDENCES X

Saroglitazar magnesium 4 mg resolved steatohepatitis without worsening of fibrosis in 39.1% of adults with metabolic dysfunction-associated steatohepatitis (MASH), compared with 13.7% receiving placebo, in the phase 2b EVIDENCES X trial presented at AASLD The Liver Meeting 2026. The trial did not meet its secondary histologic endpoint of fibrosis improvement, though the 4 mg dose improved several noninvasive fibrosis markers.1

"Many people with MASH and fibrosis also have type 2 diabetes or obesity, so we need options that address both the liver disease and the metabolic dysfunction that drives it," Naga Chalasani, MD, of Indiana University School of Medicine, said in a statement. "In this Phase 2b trial, more patients achieved resolution of steatohepatitis without worsening of fibrosis with saroglitazar than with placebo, along with improvements in lipid and glycemic parameters. These results support evaluating saroglitazar in larger, longer-term studies."

Chalasani and Arun Sanyal, MD, of Virginia Commonwealth University, served as co-principal investigators of the global trial, which Zydus Lifesciences first reported had met its primary endpoint in August 2026.2 Resmetirom and semaglutide 2.4 mg currently hold FDA accelerated approval for noncirrhotic MASH with moderate to advanced fibrosis, and several other agents remain in development.

How Did Saroglitazar Perform in EVIDENCES X?

Saroglitazar is a predominantly peroxisome proliferator-activated receptor (PPAR)-α agonist with moderate PPAR-γ activity.¹ In the multicenter, double-blind, placebo-controlled EVIDENCES X trial (NCT05011305), adults with MASH were randomized to saroglitazar magnesium 4 mg (n = 64), saroglitazar magnesium 2 mg (n = 63), or placebo (n = 62) once daily for 52 weeks. Analyses used the intention-to-treat population and were stratified by baseline diabetes status.1

Among 189 participants, the mean age was 56 years, approximately 61% were women, mean body mass index was approximately 35 kg/m², and 59% had type 2 diabetes.1 The trial enrolled patients across the US, Turkey, and Argentina.2

Steatohepatitis resolution without worsening of fibrosis occurred in 39.1% of patients receiving 4 mg and 32.4% receiving 2 mg, compared with 13.7% receiving placebo.¹ The treatment difference vs placebo was 24.9% (95% CI, 9.5-40.3; P = .002) for 4 mg and 16.5% (95% CI, 1.3-31.6; P = .033) for 2 mg.¹

Did Saroglitazar Improve Liver Fibrosis?

Fibrosis improvement of at least 1 stage without worsening of NAFLD Activity Score occurred in 34.8% of patients receiving 4 mg, 22.8% receiving 2 mg, and 24.6% receiving placebo. Neither dose differed significantly from placebo (4 mg: 10.2%; 95% CI, −6.3 to 26.6; P = .230; 2 mg: −0.9%; 95% CI, −16.7 to 14.9; P = .209).1

Noninvasive fibrosis assessments favored the 4 mg dose. Compared with placebo, saroglitazar 4 mg was associated with treatment differences of −9.50 ng/mL (95% CI, −15.3 to −3.7) for PRO-C3, −0.35 (95% CI, −0.5 to −0.2) for APRI, −0.30 (95% CI, −0.5 to −0.1) for FIB-4, and −0.53 (95% CI, −1.0 to −0.1) for ADAPT.1

The 4 mg dose also produced clinically meaningful improvements in liver enzymes, lipid and glycemic parameters, and insulin resistance, according to the investigators. Treatment was well tolerated, without significant weight gain or a drug-induced liver injury signal. The authors described the noninvasive fibrosis findings as encouraging.1

Saroglitazar magnesium was approved in India in 2020 for MASH and metabolic dysfunction-associated steatotic liver disease but remains investigational in the US for these indications.2 In primary biliary cholangitis, the US Food and Drug Administration granted Priority Review to the new drug application for saroglitazar, with a target action date of November 27, 2026, as previously reported by HCPLive.3

References:

1. Chalasani N, Lazas D, Casciato P, et al. Saroglitazar magnesium achieves resolution of steatohepatitis without worsening fibrosis in patients with MASH: results of a randomized, placebo-controlled phase 2b trial (EVIDENCES X). Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.

2. Zydus Lifesciences. Zydus announces positive topline results from completed EVIDENCES-X phase II(b) clinical trial of saroglitazar Mg in MASH. Published August 31, 2026. Accessed November 6, 2026. https://www.zyduslife.com/investor/admin/uploads/21/83/Zydus-Announces-Positive-Topline-Results-from-Completed-EVIDENCES-X-Phase-II(b)-Clinical-Trial-of-Saroglitazar-Mg-in-MASH.pdf

3. Livingston R. FDA grants Priority Review to saroglitazar NDA for primary biliary cholangitis. HCPLive. Published May 28, 2026. Accessed November 6, 2026. https://www.hcplive.com/view/fda-grants-priority-review-to-saroglitazar-nda-for-primary-biliary-cholangitis