Emerging Second-Line Therapies in PBC

While the primary biliary cholangitis (PBC) treatment landscape has long been limited to just a handful of agents with limited efficacy, 2024 saw a major shift in PBC management with the addition of 2 new second-line therapies.

Seladelpar (Livdelzi), a proliferator-activated receptor (PPAR) delta agonist, was one of these recent additions to the PBC treatment armamentarium and was a major topic of discussion at The Liver Meeting 2024 from the American Association for the Study of Liver Diseases (AASLD) in San Diego, California.

Along with a late-breaking presentation highlighting seladelpar’s sustained efficacy and long-term safety in a 2.5-year interim analysis of the ongoing open-label phase 3 ASSURE study, another abstract presentation focused on the agent’s impact on pruritus in the RESPONSE trial.

In this segment, which is part 3 of a 4-part series, Andreas Kremer, MD, PhD, MHBA, head of hepatology at University Hospital Zurich, reviews emerging second-line therapies in PBC.

Kremer provides an overview of promising advancements in the treatment of pruritus in PBC, focusing on 2 recently FDA-approved PPAR agonist therapies: elafibranor and seladelpar. He explains how these drugs target PPAR to address the underlying mechanisms of PBC. Both seladelpar, a specific PPAR delta agonist, and elafibranor, a dual PPAR alpha and delta agonist, exhibit anticholestatic and anti-inflammatory properties, making them effective options for treating the disease's root causes.

Highlighting recent clinical advancements, Kremer highlights seladelpar's performance in a phase 3 trial where the drug met its pre-specified secondary endpoint for significantly reducing pruritus severity, as measured by the numeric rating scale. He additionally called attention to a posthoc analysis from the study that revealed a strong anti-pruritic effect in certain patient subgroups, offering additional hope for tailored treatment approaches.

Editors’ note: Kremer has relevant disclosures with AbbVie, AstraZeneca, Bayer, CymaBay, Gilead, GlaxoSmithKline, Intercept, Mirum, Takeda, Ipsen, and others.

References

1. ^{Brooks A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. HCPLive. August 14, 2024. Accessed December 6, 2024. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis}
2. ^{Brooks A. Seladelpar (Livdelzi) Demonstrates Long-Term Benefit for Primary Biliary Cholangitis. HCPLive. November 15, 2024. Accessed December 6, 2024. https://www.hcplive.com/view/seladelpar-livdelzi-demonstrates-long-term-benefit-primary-biliary-cholangitis}