GASTROENTEROLOGY & HEPATOLOGY
CONFERENCE UPDATE

Seladelpar reduces cholestatic and liver injury markers in patients with PBC: Results from the RESPONSE trial

10 Apr 2024

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​STUDY DESIGN

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that primarily affects women and is characterized by the progressive destruction of bile ducts.1 This condition can lead to liver injury, fibrosis, and ultimately cirrhosis.1 To address the unmet needs of patients inadequately responding to ursodeoxycholic acid (UDCA), seladelpar, a selective peroxisome proliferator-activated receptor delta (PPARδ) agonist, has emerged as a promising treatment option.1 The phase 3 RESPONSE trial was designed to evaluate the efficacy and safety of seladelpar in patients with PBC.1

The RESPONSE trial was a placebo-controlled study involving 193 patients with PBC who had either an inadequate response to or a history of intolerance to UDCA.1 Patients were randomly assigned in a 2:1 ratio to receive either 10mg of the seladelpar (n=128) or placebo (n=65) daily for 12 months.1 The mean age of these patients was 59.5 years.1 All patients in the treatment group were female, while 78% of the placebo group were female.1

In this presentation, efficacy outcomes in the subset of patients with PBC with (n=17) or without cirrhosis (n=166) were reported and included changes from baseline in alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and total bilirubin (TB) levels.1

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FINDINGS

Efficacy endpoints:
  • Efficacy outcomes presented included changes from baseline in serum level ALP, GGT, ALT, TB and improvement in pruritus scores1
  • Rapid and sustained ALP reductions occurred with seladelpar vs. placebo in patients with (-121.4U/L vs. 23.2U/L; p<0.05) and without cirrhosis (-134.8U/L vs. -18.0U/L; p<0.0001)1
  • Rapid and sustained reductions in GGT occurred with seladelpar vs. placebo in patients with (-76.1U/L vs. 10.3U/L) and without cirrhosis (-112.4U/L vs. -23.4U/L; p<0.001)1
  • Sustained reductions in ALT occurred with seladelpar vs. placebo in patients with (-5.1U/L vs. 1.9U/L) and without cirrhosis (-12.9U/L vs. -4.7U/L; p<0.05)1
  • TB remained stable among patients with (0.17mg/dL) vs. without cirrhosis (-0.05mg/dL)1
  • Mean international normalized ratio (INR) and model for end-stage liver disease (MELD) score were similar between groups over 12 months1
  • Liver stiffness remained generally stable over 12 months in both treatment groups for patients with cirrhosis and those without cirrhosis1
Safety:
  • Among patients with cirrhosis, the overall incidence of adverse events (AEs) was reported at 89% for both arms1
  • In patients without cirrhosis, AEs were observed in 86% of the seladelpar arm and 84% of the placebo arm1
  • Serious adverse events (SAEs) occurred in 11% of both the treatment and placebo groups among those with cirrhosis, while 6% of the treatment group and 5% of the placebo group without cirrhosis reported SAEs1
  • Two patients (22%) in the placebo group with cirrhosis discontinued treatment due to AEs, whereas no patients on seladelpar discontinued for this reason1
  • In the cirrhosis subgroup, liver-related AEs were reported in 11% of the treatment group and 22% of the placebo group1
  • No muscle-related AEs were noted in the treatment group, but one patient (11%) in the placebo group experienced such an event1
  • No treatment-related SAEs were reported in either group1

 

“In patients with PBC and cirrhosis, seladelpar decreased cholestatic and liver injury markers compared with placebo, similar to effects seen in patients without cirrhosis in the RESPONSE trial”

Dr. Alejandra Villamil

The Liver Autoimmunity Unit,

Hospital Italiano de Buenos Aires, Buenos Aires,

Argentina

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References

  1. Villamil A, et al. Efficacy and Safety of Seladelpar in Patients with Primary Biliary Cholangitis and Compensated Cirrhosis in the Phase 3 Placebo-Controlled RESPONSE Trial: 3-Year Results. Presented at the 66th American Association for the Study of Liver Diseases (AASLD) Annual Meeting 2024; November 15-19, 2024.

Seladelpar
Cholestatic and liver injury
PBC

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