The Future of PBC Management, Pipeline Developments

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 final 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 pipeline developments they are most looking forward to. Hirschfield answers first, describing his excitement at the prospect of having new on-label options for his patients that he feels he can use safely and effectively. Specifically, he mentions the potential he sees in ileal bile acid transporter (IBAT) inhibitors and their impact on pruritus. Trivedi points to the development of clinical trials assessing what he deems to be more complex facets of PBC and symptoms that are more difficult to manage, including fatigue and cognitive impairment.

Reau concludes the discussion by saying she hopes it helps clinicians understand how their cholestatic toolbox is “rapidly filling” and ways in which they can leverage these new tools to help their patients achieve “remarkable results,” a sentiment Hirschfield and Trivedi both echoed.

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.