Recent Advances in Second-Line Therapies in PBC

In recognition of the US Food and Drug Administration accelerated approval of Gilead's seladelpar (Livdelzi) and other recent evolutions in primary biliary cholangitis (PBC), the latest HCPLive Special Report spotlights a conversation between a trio of subject matter experts on the latest advancements in PBC and their implications for disease management.

A chronic and progressive autoimmune liver disease affecting intrahepatic bile ducts, common symptoms of PBC include ​​jaundice, pruritus, and fatigue. Ursodeoxycholic acid (UDCA) has long been the mainstay of treatment for PBC and continues to be the only first-line therapy. However, many patients do not respond to or are unable to tolerate UDCA, underscoring the need for more treatment options to prevent progression to cirrhosis and eventual liver failure as well as to improve symptoms most negatively impacting patients. In the past 3 months alone, the PBC treatment landscape has seen the addition of 2 new therapeutic options with the accelerated approvals of seladelpar and elafibranor, both of which are proliferator-activated receptor agonists shown to reduce alkaline phosphatase.

In the second segment of our 6-part HCPLive Special Report on the evolving landscape of PBC management, moderator Nancy Reau, MD, asks Palak Trivedi, MD, PhD, about the evolving landscape of second-line therapies for PBC, focusing on the transition from traditional treatments to more advanced options. Historically, obeticholic acid (OCA) was the only licensed second-line therapy, a farnesoid X receptor (FXR) agonist that reduced bile acid synthesis and promoted bile acid outflow. Trivedi describes how, when combined with UDCA, OCA offers complementary anti-inflammatory and anti-fibrotic effects, making it a cornerstone of PBC management.

However, the introduction of new PPAR agonists marks a significant advancement in PBC treatment options. These agents, including the newer generation PPAR agonists such as elafibranor and seladelpar, work through various isoforms to downregulate bile acid synthesis enzymes and enhance bile acid secretion. By upregulating bile acid transporters and promoting detoxification at the gene level, these therapies offer a novel approach to reducing bile acid toxicity in cholestatic diseases. Trivedi highlights the importance of these advancements, noting their potential to complement existing therapies like OCA and UDCA, as well as their promise in future comparative studies.

Check out the other segments in this series:

• Part 1: Shifting Treatment Goals, Timelines in PBC
• Part 2: Recent Advances in Second-Line Therapies
• Part 3: Assessing PBC Treatment Options, Sequencing
• Part 4: Considerations for Treatment Sequencing in PBC
• Part 5: Impact of Next-Generation PPAR Agonists on PBC Management
• Part 6: The Future of PBC Management, Pipeline Developments

Panelists

• Nancy Reau, MD (Moderator): associate director of solid organ transplantation and section chief of hepatology at Rush University Medical Center
• Palak Trivedi, MD, PhD: associate professor and honorary consultant hepatologist and clinical research director for industry engagement at the University of Birmingham
• Gideon Hirschfield, PhD, MB BChir: director of the Autoimmune Liver Disease Program at University Health Network’s Francis Family Liver Clinic and Toronto Centre for Liver Disease and Lily and Terry Horner Chair in Autoimmune Liver Disease Research at the University of Toronto

Relevant disclosures for Reau include Eiger, Gilead, AbbVie, Salix, and Intercept. Relevant disclosures for Trivedi include Bristol Myers Squibb, Gilead, Intercept, CymbaBay, and others. Relevant disclosures for Hirschfield include CymaBay, Escient, Gilead, GSK, HighTide, Intercept, Ipsen, Mirum, and Pliant.