Andreas E Kremer1,2, Marlyn J Mayo3, Gideon Hirschfield4, Cynthia Levy5, Christopher L Bowlus6, David E Jones7, Alexandra Steinberg8, Charles A McWherter8, Yun-Jung Choi8. 1. Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland. 2. Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany. 3. Division of Digestive and Liver Diseases, University of Texas SW Medical Center, Dallas, TX, USA. 4. Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada. 5. Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine. Miami, Florida, USA. 6. Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of California Davis, Sacramento, CA, USA. 7. Clinical and Translation Research Institute, Newcastle University, Newcastle upon Tyne, UK. 8. CymaBay 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.
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.
Authors: Erica Nicola Lynch; Claudia Campani; Tommaso Innocenti; Gabriele Dragoni; Maria Rosa Biagini; Paolo Forte; Andrea Galli Journal: World J Hepatol Date: 2022-06-27