Navigating Evolutions, Uncertainties in PBC Care, with Craig Lammert, MD

2024 was a historic year for primary biliary cholangitis (PBC) as the field of hepatology saw the addition of 2 new second-line treatment options with the FDA accelerated approvals of Ipsen’s elafibranor (Iqirvo) and Gilead’s seladelpar (Livdelzi).1,2

A chronic and progressive autoimmune liver disease affecting intrahepatic bile ducts, common symptoms of PBC include ​​jaundice, pruritus, and fatigue. Ursodeoxycholic acid 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 it, 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 second part of an interview with HCPLive, Craig Lammert, MD, an associate professor of medicine at Indiana University School of Medicine and executive director for the Autoimmune Hepatitis Association, discusses the adoption of elafibranor and seladelpar in clinical practice and barriers to their uptake.

He says that while clinical trial data for both agents has translated well into real-world practice, access remains a significant issue, with many insurance plans delaying coverage for newly approved medications by 6 months to more than a year and leaving clinicians with difficult decisions about whether to wait or use alternative therapies.

Lammert goes on to highlight what he refers to as "alkaline phosphatase purgatory"—those with persistently elevated but not severely abnormal alkaline phosphatase levels. This group, comprising nearly a third of PBC patients, often does not qualify for new second-line treatments despite evidence suggesting they remain at higher risk for liver-related complications, particularly if bilirubin levels exceed 0.6 mg/dL.

He notes that understanding the impact elafibranor and seladelpar have on quality of life will also be important, acknowledging that while disease control and transplant avoidance are critical goals, addressing pruritus and fatigue are important to patients and must also be prioritized.

Looking ahead, Lammert emphasizes that it will be important to consider what can be done for patients beyond the “therapeutic ceiling” of these new agents as well as to explore dual agent therapy or additive therapies to “rescue” difficult-to-treat patients.

Check out part 1 of the interview here: The Evolving Primary Biliary Cholangitis Landscape, with Craig Lammert, MD

Editors’ note: Lammert has relevant disclosures with Eli Lilly, Kezar Life Sciences, and the Autoimmune Hepatitis Association.

References

1. Brooks A. FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC. HCPLive. June 10, 2024. Accessed March 24, 2025. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-elafibranor-iqirvo-for-pbc

2. Brooks A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. HCPLive. August 14, 2024. Accessed March 24, 2025. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis