Seladelpar Improved Measures of Pruritus, Sleep, and Fatigue and Decreased Serum Bile Acids in Patients with Primary Biliary Cholangitis.

Abstract

BACKGROUND & AIMS\nPrimary biliary cholangitis (PBC) can result in life-altering cholestatic pruritus and fatigue, but treatment options are limited. Seladelpar, a peroxisome proliferator-activated receptor-delta (PPARδ) agonist, has demonstrated potent anti-cholestatic effects in clinical studies. This open-label, uncontrolled phase 2 study in PBC patients evaluated the effects of 1-year of seladelpar treatment on measures of pruritus and quality of life.\n\n\nMETHODS\nSelf-reported experiences of 101 PBC patients were collected at baseline and after 1 year of seladelpar treatment using the pruritus visual analogue scale (VAS), 5D-itch scale, and PBC-40 questionnaires along with bile acid profiles.\n\n\nRESULTS\nIn patients with moderate to severe pruritus, substantial improvement in pruritus was seen in 58% and 93% of patients in 5/10 mg and 10 mg treatment groups, respectively. After 1 year, patients reporting improvement substantially outnumbered those who worsened in the total 5-D itch (including individual domains) and PBC-40 (itch and fatigue domains) questionnaires. Improvement in sleep disturbance at 1-year was reported in 81% (5/10 mg) and 78% (10 mg) of the patients with baseline itch-related sleep disturbance by 5-D itch score with similar results using the PBC-40 sleep questionnaire. Seladelpar-treated patients had significant reductions of 46% (5/10 mg) and 31% (10 mg) in the serum bile acid precursor C4 and reductions of up to 38% in serum bile acids.\n\n\nCONCLUSIONS\nSeladelpar treatment for 1 year led to consistent improvement in both symptom burden and biochemical response suggesting its potential as a single agent to address two key unmet needs in PBC patients.