Seladelpar

Intercept Pharmaceuticals is withdrawing its liver drug Ocaliva (obeticholic acid) from US shelves at the FDA's request, capping years of safety concerns and regulatory scrutiny. The move follows reports of liver failure in patients with primary biliary cholangitis (PBC), including deaths and transplants, even among those without advanced cirrhosis."We continue to believe the totality of clinical and real-world evidence supports Ocaliva's use for appropriate patients," said Vivek Devaraj, Intercept's US president. "While our view of Ocaliva's benefit-risk profile differs from FDA's, we respect its request and have made this difficult decision to provide clear guidance for patients and prescribers."The FDA has also ordered a halt to every Intercept trial of Ocaliva in the US.Cleared in 2016 under the FDA's accelerated pathway, the FXR agonist became entrenched as a second-line treatment option for PBC patients in combination with ursodeoxycholic acid in patients with an inadequate response to ursodeoxycholic acid (UDCA) or as monotherapy those who could not tolerate UDCA.However, its nine-year run on the market has been marred by the inclusion of boxed warnings – including one tied to dosing restrictions in patients with more advanced disease, and then another further restricting its use due to post-marketing reports of serious liver injury and liver failure in PBC patients with advanced cirrhosis – as well as a failed expansion into metabolic dysfunction-associated steatohepatitis. Regulators in Europe have already ordered the drug's withdrawal.Intercept, which was acquired by Italy's Alfasigma in 2023, said it will work with the FDA on the transition process.The US retreat comes amid a reshaping of the PBC market following the back-to-back approvals last year Gilead Sciences' Livdelzi (seladelpar) and Ipsen's Iqirvo (elafibranor), both PPAR agonists. Livdelzi so far appears to have the upper hand, according to a recent FirstWord survey of US specialists, with nearly two-thirds of respondents saying they prefer the drug over other second-line rivals, though pricing and coverage could hinder uptake (see – Physician Views Results: Livdelzi emerges as favourite among rivals, but headwinds haunt its path).Meanwhile, Zydus is preparing a US filing for saroglitazar, a dual PPAR alpha/gamma agonist that recently met its primary endpoint in a late-stage trial.

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.