Seladelpar benefit in PBC sustained at 3 years

The selective PPARδ* agonist seladelpar continues to demonstrate benefit in patients with primary biliary cholangitis (PBC) in the long-term pooled analysis from the ongoing open-label phase III ASSURE trial.

“By month 30, seladelpar resulted in a durable and sustained composite biochemical response (BCR) in 81 percent of patients and an alkaline phosphatase (ALP) normalization rate of 41 percent,” said the researchers. Of note, about three-quarters (73 percent) of participants achieved the composite BCR endpoint at months 12 and 24.

As for the ALP levels, the improvement was evident as early as month 1 and was sustained through month 30. “A lower ALP level is considered the main result that shows seladelpar is working,” said the researchers.

About two-thirds of participants with elevated alanine aminotransferase (ALT) at baseline achieved normal ALT levels at months 12 and 24 (61 percent and 66 percent, respectively). By month 30, 90 percent of those with increased baseline ALT have achieved this outcome. In 37 patients, the mean ALT percent change at month 30 was -29 percent from baseline. The marked reduction achieved by month 3 was maintained out to month 30.

Total bilirubin (TB) and gamma-glutamyl transferase (GGT) levels also dropped as early as month 1 and were sustained up until month 30 in 37 patients (mean percent changes from baseline, -5 percent [TB] and -4.2 percent [GGT]). Aspartate aminotransferase levels remained stable through month 30.

In evaluable patients with moderate-to-severe pruritus at baseline (n=99), the mean change in the pruritus Numeric Rating Scale from baseline at 6 months was -3.3. According to the investigators, this was a robust improvement in pruritus. [DDW 2025, abstract Mo1616]

Exposure-adjusted adverse events (AEs) were reported in 85.8, 70, and 63 patients per 100 patient-years (PY) at months 12, 24, and 36, respectively. Overall, the most common exposure-adjusted AEs at year 3 were COVID-19, pruritus, and nausea (11.5, 6.8, and 5.2 patients per 100 PY). There were no treatment-related serious AEs. One fatal outcome, autoimmune haemolytic anaemia, was deemed unrelated to the investigational drug.

The rates of exposure-adjusted liver-, muscle-, and renal-related AEs either remained stable or dropped over 3 years of seladelpar exposure. Most AEs of interest were low-grade.

“Seladelpar continues to appear safe and well tolerated, showing no new safety signals or changes in the frequency of AEs after up to 3 years of exposure,” said the investigators.

Current findings boost interim results

ASSURE evaluated the first-in-class delpar seladelpar in PBC patients who rolled over from the phase III RESPONSE trial or had previously participated in seladelpar legacy** studies. The parent trials required an inadequate response or intolerance to first-line ursodeoxycholic acid. A total of 337 patients (mean age 58.1 years, 94 percent women, 7 percent Asian) received seladelpar 10 mg daily. Of these, 124 had ≥24 months of seladelpar exposure, and 34 reached 30 months on study. At baseline, mean ALP was 287.5 U/L, mean TB was 0.8 mg/dL, and 16 percent had cirrhosis.

In the interim analysis of ASSURE, seladelpar has demonstrated a durable effect on markers of cholestasis and liver injury, which was sustained for up to 2 years among participants who have continued seladelpar in ASSURE after completing the RESPONSE trial. This analysis also showed that treatment effects with seladelpar mirrored those reported among legacy patients who have started seladelpar in ASSURE. [EASL 2024, abstract ST-13]

The current results build on the interim findings, reinforcing the benefit of seladelpar in PBC, a chronic, progressive autoimmune cholestatic liver disease affecting about one in 1,000 women >40 years. [J Hepatol 2017;67:145-172]