Author information

• ¹Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland.
• ²Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany.
• ³Division of Digestive and Liver Diseases, University of Texas SW Medical Center, Dallas, TX, USA.
• ⁴Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
• ⁵Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine. Miami, Florida, USA.
• ⁶Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of California Davis, Sacramento, CA, USA.
• ⁷Clinical and Translation Research Institute, Newcastle University, Newcastle upon Tyne, UK.
• ⁸CymaBay Therapeutics, Inc., Newark, CA, USA.

Abstract

Background & aims: Primary 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.

Methods: Self-reported experiences of 101 PBC patients were collected at baseline and after 1 year of seladelpar treatment using the pruritus visual analog scale (VAS), 5D-itch scale, and PBC-40 questionnaires along with bile acid profiles.

Results: In 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.

Conclusions: Seladelpar 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.