Seladelpar Treatment Improved Overall Health and Quality of Life in Patients with Primary Biliary Cholangitis

An in-depth look at data from the phase 3 RESPONSE trial, presented at The Liver Meeting 2025, in Washington, D.C., showed that patients with primary biliary cholangitis (PBC) treated with seladelpar achieved meaningful improvements in quality of life and reductions in PBC symptoms over 12 months of treatment. 

PBC is associated with a high burden of symptoms, including pruritus and fatigue, which have a significant impact on overall health and quality of life. Seladelpar, a selective peroxisome proliferator–activated receptor delta (PPARδ) agonist indicated as a second-line therapy for PBC, has shown promise in improving not only biomarkers of disease progression but also the severity and duration of pruritus caused by PBC. Patients with PBC enrolled in the pivotal phase 3 RESPONSE trial reported worse general health and well-being after the PBC diagnosis compared with the period preceding the diagnosis. In a post-hoc analysis of data from the trial, researchers used three questions from the Primary Biliary Cholangitis Quality of Life Measure Questionnaire (PBC-40), a disease-specific tool, to assess the impact of seladelpar treatment on general health and well-being among patients with PBC. 

Participants in the trial completed PBC-40 at enrollment and at subsequent timepoints, up to month 12 of treatment. The questions were designed to assess the participants’ current general health status, their health before the PBC diagnosis, and the evolution of their health status over 1 year of treatment. Scores ranged from 1 to 5, with lower scores denoting better general health and well-being. 

After 12 months, general health improved at greater rates for patients treated with seladelpar than for those who took placebo. Higher percentages of patients treated with seladelpar reported “much better” health compared with those assigned to placebo, regardless of pruritus severity at baseline. In the overall trial cohort, the proportion of participants reporting excellent or very good health increased from approximately 15% at baseline to 22% at month 12 among treated patients and decreased by almost 2% among those receiving placebo. In patients with moderate-to-severe pruritus, excellent health rose from 5.6% to 8.3% with seladelpar and continued to decline for those receiving placebo; after 1 year of enrollment, none of the participants with moderate-to-severe pruritus in the placebo group reported excellent or very good health status. 

An additional analysis from RESPONSE showed that the reduction in itch severity achieved with seladelpar decreased the impact of PBC on patients’ daily activities, including their social interactions, work or school activities, and their ability to perform household tasks. 

Up to 80% of patients with PBC experience pruritus, a bothersome symptom that adversely affects sleep and quality of life (Trivella J et al. Hepatol Commun 2023;7:e0179). In the RESPONSE trial, seladelpar significantly decreased pruritus in patients with PBC with moderate-to-severe pruritus at baseline (defined as a score of 4 or greater on the pruritus NRS scale) and in the overall trial population, compared with placebo. Improvement in pruritus was documented as early as 1 month after starting treatment with seladelpar, and a statistically significant difference compared to the placebo group was reached after 6 months of treatment. 

New data presented at The Liver Meeting 2025 provided a deeper understanding of the patient perspective and detailed the impact that treatment with seladelpar had on quality of life. The analysis provided valuable information about the distribution and duration of pruritus, as well as the disability related to this symptom, which were not previously captured by instruments used to assess pruritus in the RESPONSE trial. After 12 months of treatment with seladelpar, patients with moderate-to severe pruritus at baseline reported spending fewer hours per day experiencing itch compared with those who received placebo. The daily duration of itch decreased progressively with seladelpar across the entire treated population and it generally remained stable in the placebo group. The distribution of itch across the body areas was also reduced over 12 months, regardless of pruritus scores at baseline. Seladelpar-treated patients had a 38% decrease in the average number of itchy body regions after 12 months of therapy compared with those who received placebo. 

The data reflected positive changes in the impact of pruritus on daily activities, including leisure and social activities, the ability to perform housework and errands, and participation in work and school activities. The pruritus-related disability was reduced significantly in all treated patients compared with those in the placebo group. 
“These data suggest that seladelpar as a second-line therapy may fulfill an unmet need in PBC given the high prevalence and impact of pruritus on daily activities,” the authors said.