Palak Trivedi, MD, PhD

In this video segment, Reau, Trivedi, and Hirschfield discuss pipeline developments and other advances in primary biliary cholangitis they are most looking forward to.

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 

 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:

Shifting Treatment Goals, Timelines in PBC

Assessing PBC Treatment Options, Sequencing

Considerations for Treatment Sequencing in PBC

Impact of Next-Generation PPAR Agonists on PBC Management

: associate director of solid organ transplantation and section chief of hepatology at Rush University Medical Center

 associate professor and honorary consultant hepatologist and clinical research director for industry engagement at the University of Birmingham

 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.

Videos

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 

 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.

In this video segment, Reau, Trivedi, and Hirschfield discuss how treatment sequencing in PBC has evolved over time with the emergence of new second-line therapies and considerations for determining sequencing.

Considerations for Treatment Sequencing in Primary Biliary Cholangitis

 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 controversies regarding the sequencing of treatments. Hirschfield responds that although he does not think the field is completely certain about sequencing, it has generally included licensed therapies first, and he expects it to continue to change as more choices of licensed therapies become available. As a whole, he expresses excitement about having the choice to sequence therapies in PBC compared to where the field was in 2016.

Trivedi also highlights 3 things he considers when determining sequencing: policy, patient phenotype, and the regulatory pathway leading to market entry. He places particular emphasis on patient phenotype but acknowledges the importance of effectively navigating all 3 for optimizing patient outcomes in PBC management.

In this video segment, Reau, Trivedi, and Hirschfield discuss the EMA opinion on obeticholic acid and its impact on discussions about second-line therapies amid the influx of new treatment options available for patients.

Assessing PBC Treatment Options, Determining Sequencing

 Special Report on the evolving landscape of PBC management, moderator Nancy Reau, MD, asks Gideon Hirschfield, PhD, MB BChir, about how the recent European Medicines Agency (EMA) opinion on obeticholic acid (OCA) has impacted discussions with his patients about second-line therapies. Acknowledging potential misinterpretation of what the EMA message meant, Hirschfield describes the importance of having multiple treatment options and delves into the complexities of sequencing therapies for PBC patients, a critical consideration given the expanding array of treatment options.

Specifically, he discusses the challenges clinicians face in making decisions about which therapies to use and in what order, especially in the context of varying patient severity and the specific mechanisms of each therapy. Ultimately, Hirschfield emphasizes the goal is to achieve the best possible outcomes by strategically combining and sequencing treatments to maximize efficacy and minimize adverse effects.

Palak Trivedi, MD, PhD

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