Real-world data support seladelpar use in PBC patients switching from obeticholic acid

“Biochemical improvements were seen with seladelpar initiation among both the OCA-switch and and [second-line]-seladelpar groups,” write the investigators in a poster at AASLD The Liver Meeting in Washington, DC, USA.

They note the inclusion of an OCA-switch group of patients, following the recent withdrawal of OCA from the US market, “creating a need for patients to switch to other PBC treatments.”

The study involved 130 patients with PBC who switched from OCA to seladelpar and 266 who initiated second-line seladelpar as a monotherapy or in addition to UDCA. The OCA switch group did so within a mean of 8 days, during which they did not receive other second-line treatments, such as fenofibrate or elafibranor. Most of the patients switched without a gap in treatment, and the mean duration of OCA use prior to switching was 420 days.

Participants in the two groups were aged a mean of 58–59 years and the majority (88–91%) were women. The mean duration of PBC was 3.3–5.6 years, and 11.5% of the OCA-switch group and 18.4% of the second-line seladelpar group had cirrhosis.

“Metabolic comorbidities and metabolic dysfunction–associated steatotic liver disease were common in both groups, with greater prevalence in the [second-line] seladelpar group,” observe Christopher Bowlus (University of California Davis School of Medicine, Sacramento, California, USA, and colleagues.

After a mean duration of 4 months of treatment for the OCA-switch group and 3 months for the second-line seladelpar group, the proportion of patients with an alkaline phosphatase (ALP) level below 1.67 times the upper limit of normal (ULN) increased from a respective 54.8% and 52.5% to 83.3% and 74.5%.

ALP decreased by a mean of 64 U/L in patients who switched from OCA to seladelpar, from 235 U/L to 171 U/L, and by a mean of 96 U/L in those initiating seladelpar, from 290 U/L to 194 U/L.

Among participants with safety data available for at least 30 days after starting seladelpar, laboratory tests in both groups “were generally similar” to those measured within 90 days prior to initiation, note Bowlus et al.

The proportion of patients with an alanine aminotransferase or aspartate aminotransferase level above three times ULN was 1.5% before and after treatment in the OCA switch group, and 2.6% versus 0.8% in the second-line seladelpar group, with similar findings for creatinine kinase levels above 1 times ULN, at a respective 1% versus 0%, and 1.5% versus 1.5%.

The mean estimated glomerular filtration levels remained stable in both groups, at 90.6 mL/min per 1.73 m² before and 89.0 mL/min per 1.73 m² after treatment in the OCA switch group, and 91.4 versus 91.7 mL/min per 1.73 m² in the second-line seladelpar group.

The researchers acknowledge: “Given that seladelpar treatment received accelerate FDA approval in 2024, the follow-up time is limited,” and therefore “further evaluation with extended follow-up is warranted.”

Nevertheless, they conclude that “seladelpar may be an effective and safe alternative for patients with PBC switching from OCA or initiating seladelpar as [second-line] therapy in the real-world setting.”