Updates in Primary Biliary Cholangitis Care, with Allysa Saggese, NP

The primary biliary cholangitis (PBC) treatment landscape has undergone significant developments in the past few months with the addition of a pair of newly FDA-approved peroxisome proliferator-activated receptor (PPAR) agonists, elafibranor (Iqirvo) and seladelpar (Livdelzi).^1,2

Although ursodeoxycholic acid (UDCA) has long served as the first-line treatment for patients with PBC and has demonstrated a notable impact on transplant-free survival as well as the development of fibrosis and esophageal varices, many patients do not have an adequate response to treatment or are unable to tolerate it, underscoring the need for second-line therapies.^1,2

Since it was first granted FDA accelerated approval in 2016, obeticholic acid (Ocaliva) has been the only second-line treatment option in PBC. However, following a negative opinion from a US Food and Drug Administration Gastrointestinal Drug Advisory Committee and with a quickly-approaching October 15, 2024, Prescription Drug User Fee Act (PDUFA) target action date looming around the corner, obeticholic acid’s future in PBC appears to be less than certain.³

“It's very important to have second-line treatments available. If someone is unable to tolerate the first-line treatment, we want to be able to provide them with something,” Allysa Saggese, NP, a nurse practitioner in liver disease and transplantation at Weill Cornell Medicine, explained to HCPLive. “The goal here is to normalize alkaline phosphatase. That's been a big discussion in the community, and we want to be able to provide some way to do that.”

Although she noted the impact of the approvals of elafibranor and seladelpar is still evolving, Saggese described these developments as “exciting,” citing the potential benefits of having more options to offer patients who may be intolerant to both ursodeoxycholic acid and obeticholic acid.

She went on to point out how treatment goals have shifted from alkaline phosphatase ≤1.67×upper limit of normal to alkaline phosphatase normalization, also describing accelerated treatment timelines because of how rapidly the newer second-line therapies have shown improvement in clinical trials as well as what conversations about treatment with patients look like with so many therapies now available to them.

“One thing that I keep learning through discussing all of the medications, treating my patients, and being a part of the trials is that we might need to be more conscious of how we are talking about PBC symptoms,” Saggese said, describing her own experiences inquiring about itch and the importance of making patients aware that it may be a symptom or side effect of PBC. “We need to make sure we're providing the most comprehensive kind of care for these patients.”

References

1. ^{Brooks, A. FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC. HCPLive. June 10, 2024. Accessed October 8, 2024. 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 October 8, 2024. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis}
3. ^{Brooks, A. Nancy Reau, MD: Obeticholic Acid’s Future in PBC After FDA Advisory Committee Meeting. HCPLive. September 20, 2024. Accessed October 8, 2024. https://www.hcplive.com/view/nancy-reau-md-obeticholic-acid-future-pbc-fda-advisory-committee-meeting}