Elafibranor

Zydus plans to share full data from the trial at an upcoming scientific congress.\n Zydus Therapeutics has racked up a phase 2b/3 win in primary biliary cholangitis (PBC), clearing the path to a filing to establish the company as a challenger to Gilead Sciences, Intercept Pharmaceuticals and Ipsen.The phase 3 part of the trial randomized 149 people to receive the PPAR agonist saroglitazar or placebo. After 52 weeks of daily oral dosing, 48.5% of patients on the Zydus drug met the biochemical response, achieving the primary endpoint of the trial. Zydus plans to discuss the data with the FDA with hopes of filing for approval in the first quarter of 2026.If approved, saroglitazar will enter a market served by other drugs, including rival PPAR agonists. The FDA approved two PPAR agonists in PBC last year, clearing Gilead’s Livdelzi and Ipsen’s Iqirvo to compete for the market with Intercept’s FXR agonist Ocaliva.Gilead reported (PDF) a 62% biochemical response rate in the study that supported approval of Livdelzi. Ipsen’s Iqirvo achieved (PDF) a 51% biochemical response rate in its pivotal trial. Unlike the PPAR agonists, Intercept\'s Ocaliva carries a boxed warning. The FDA rejected a filing for full approval of the product in November—while leaving the accelerated nod in place—and flagged liver injury reports in December. When Zydus completed enrollment in its phase 3 trial last year, the lead principal investigator reported (PDF) “growing optimism” that saroglitazar can improve on the efficacy, safety and tolerability of existing treatments. The investigator was speaking before the approvals of Livdelzi and Iqirvo.The data shared by Zydus to date preclude cross-trial comparisons to assess whether saroglitazar has any potential advantages over the incumbents. The lack of a placebo response rates in Zydus’ release limits efficacy comparisons, though the absolute response rate of saroglitazar falls short of its rivals. The biotech\'s release also lacks data on itching and fatigue, symptoms the investigator named as areas in which Zydus may have an edge.  Zydus plans to share full data from the trial at a future scientific congress.

Zydus Therapeutics is planning to file for FDA approval of its liver disease candidate early next year after saroglitazar met the primary endpoint of the EPICS-III Phase IIb/III trial in patients with primary biliary cholangitis (PBC) — setting it up to compete with Gilead Sciences and Ipsen. Zydus is the US-based speciality arm of Indian pharma Zydus Lifesciences. Similar to Gilead's Livdelzi (seladelpar) and Ipsen's Iqirvo (elafibranor), saroglitazar is a PPAR agonist, but while the former is directed against the PPAR delta receptor and the latter agonises PPAR alpha and delta, Zydus' candidate targets the alpha and gamma receptors. Both saroglitazar's potential competitors were approved last summer, offering new treatments to a disease space that previously had only one option, and one plagued with safety concerns at that — Alphasigma's Ocaliva (obeticholic acid).For more insight on how physicians are responding to Livdelzi and Iqirvo's launches, see Physician Views Results: Livdelzi emerges as favourite among rivals, but headwinds haunt its path and Physician Views Results: Gilead's fashionably late arrival for Livdelzi in PBC has doctors flocking.Besting placeboThe Phase III portion of EPICS-III randomised 149 patients with PBC who had an inadequate response or intolerance to standard-of-care ursodeoxycholic acid to receive placebo or a 1-mg oral dose of saroglitazar once daily. Zydus' candidate met its primary composite endpoint, with a statistically significant treatment difference in achieving a biochemical response of 48.5% that favoured saroglitazar over placebo at week 52. The study defined biochemical response as alkaline phosphatase <1.67x upper limit of normal and with a ≥15% decrease relative to baseline; total bilirubin also needed to be ≤ upper limit of normal. The enzyme and bilirubin, a yellow pigment, are predictors of PBC disease progression. Saroglitazar also met a key secondary goal, which measured the proportion of participants with complete normalisation of alkaline phosphatase. According to Zydus, the PPAR agonist was well tolerated, with adverse events "generally balanced" between it and the placebo group. "The EPICS-III results reinforce our commitment to advancing novel treatments for chronic liver disease — an area of high unmet medical need and growing global impact," commented Zydus Lifesciences Chairman Pankaj Patel. "Saroglitazar is the first PPAR alpha/gamma agonist to demonstrate positive Phase III data in patients with PBC and has the potential to bring real value to both patients and their healthcare providers who may need more options."The company plans to file a marketing application for saroglitazar — which has fast track designation from the FDA — in the first quarter of 2026.