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Impact of Next-Generation PPAR Agonists on PBC Management
Author(s):
In this video segment, Reau, Trivedi, and Hirschfield discuss how the emergence of second-generation PPAR agonists like seladelpar and elafibranor impact PBC management.
In recognition of the US Food and Drug Administration accelerated approval of 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 fifth segment of our 6-part HCPLive Special Report on the evolving landscape of PBC management, moderator Nancy Reau, MD, asks Palak Trivedi, MD, PhD, and Gideon Hirschfield, PhD, MB BChir, about how the emergence of second-generation PPAR agonists impacts the management of patients with PBC, especially those experiencing pruritus. Trivedi describes his own practice in the United Kingdom and says that although he does not anticipate it will have an immediate major impact on patients he currently treats with obeticholic acid because he believes they will still benefit from that treatment, he also acknowledges that his perspective may change with time.
Hirschfield describes excitement for patients who now have more than one drug label to read. He also mentions the conservative nature of the US Food and Drug Administration and the significance of their recognition of pruritus improvement with seladelpar. Although he believes the future will include combination therapies and their exploration in clinical trials, for now, Hirschfield says he believes providers are going to look at labels and try to make decisions that will benefit patients most.
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.
