The Evolving Primary Biliary Cholangitis Landscape, 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 elafibranor (Iqirvo) and 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 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, outlines the shifting landscape of treatment response metrics and the latest advancements in second-line therapy for PBC.

He begins by highlighting how traditional biochemical response criteria may not fully predict long-term clinical benefits. Specifically, Lammert points to use of the Toronto criteria, 1.67 x upper limit normal alkaline phosphatase at 1 year, to predict patients who will do well on ursodeoxycholic acid, noting that meeting this criteria has not always been linked with good long-term data and outcomes.

“I think we're seeing a little bit of a change in landscape, specifically because we’re realizing that maybe up to 50% of patients were not meeting these metrics,” Lammert said. “I think this has spawned and increased the pharmaceutical perspective and pursuit of other agents. We've been excited recently because now, as we all know, we had 2 FDA-approved compounds this past year that were poised to be transformative for patients who were hard to control or not meeting biochemical remission through a few different parameters.”

Elafibranor and seladelpar, both of which are peroxisome proliferator-activated receptor agonists, were granted accelerated approval for the treatment of PBC in combination with ursodeoxycholic acid in adults who have had an inadequate response to ursodeoxycholic acid, or as monotherapy in patients unable to tolerate ursodeoxycholic acid.1,2

Lammert goes on to discuss the broader role of PPAR agonists in PBC management, noting that existing agents like bezafibrate and fenofibrate have demonstrated long-term benefits. Although these older PPAR agents have a longer track record, he says he believes the newly approved PPAR-targeting therapies may follow a similar path.

“The other PPARs, fenofibrate and bezafibrate, certainly have the leg up in terms of duration of observation and follow-up,” Lammert said. “I suspect, and I think most of us in the field think, the new PPARs will follow suit with time.”

Looking ahead, Lammert emphasizes the need for continued research to establish whether response criteria for these new agents correlate with meaningful survival improvements. He notes real-world data and long-term follow-up studies will be critical in validating their efficacy, particularly given the challenges of conducting large-scale trials once therapies are already on the market.

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 21, 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 21, 2025. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis