Efficacy and safety of bempedoic acid in patients with heterozygous familial hypercholesterolemia: analysis of pooled patient-level data from phase 3 clinical trials.

Background: Patients with heterozygous familial hypercholesterolemia (HeFH) often cannot reach guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals despite multidrug therapy.
Objective: To evaluate the efficacy and safety of bempedoic acid as an add-on therapy for lowering LDL-C in patients with HeFH.
Methods: Pooled data from two 52-week phase 3 clinical trials of patients with atherosclerotic cardiovascular disease and/or HeFH receiving maximally tolerated statin therapy (randomized 2:1 to bempedoic acid or placebo) were analyzed by HeFH status. Endpoints included changes from baseline to week 12 (and up to week 52) in LDL-C and other lipid parameters, achievement of LDL-C goals, and safety.
Results: A total of 217 (bempedoic acid, 146; placebo, 71) patients with HeFH and 2,792 (bempedoic acid, 1,864; placebo, 928) without HeFH were included (mean baseline LDL-C, 172.8 mg/dL and 102.6 mg/dL, respectively). Bempedoic acid significantly lowered LDL-C at week 12 vs. placebo regardless of HeFH status (with HeFH, -21.2%; without HeFH, -18.2% [both P<0.0001]). Bempedoic acid significantly reduced other lipid parameters and high-sensitivity C-reactive protein vs. placebo regardless of HeFH status (all P≤0.01). Among patients with HeFH treated with bempedoic acid, 32% and 27% achieved LDL-C <100 mg/dL at weeks 12 and 52, respectively. Overall treatment-emergent adverse event incidence was comparable across all four groups (74.7-77.5%).
Conclusion: Bempedoic acid significantly lowered LDL-C levels vs. placebo and was generally well tolerated in all patients, with no new safety findings in patients with HeFH, despite more intensive lipid-lowering therapy in patients with vs. without HeFH.
Competing Interests: Declaration of competing interest PBD has received institutional research grant(s)/support from Regeneron, Regenxbio, and Retrophin/Travere Therapeutics, and has served as a consultant for Akcea/Ionis, Esperion Therapeutics, Inc., Kaneka, Novo Nordisk, and Regeneron. MB has received research grant(s)/support from Amgen, Daiichi Sankyo, Sanofi, Mylan, and Valeant, and has served as a consultant for Abbott/Mylan, Abbott Vascular, Amgen, Daiichi Sankyo, Esperion Therapeutics, Inc., Freia Pharmaceuticals, KRKA, Lilly, MSD, NewAmsterdam Pharma, Novo Nordisk, Pfizer, Polfarmex, Polpharma, Regeneron, Sanofi-Aventis, Servier, Teva, and Zentiva. ALC has received research grant(s)/support from Amgen, Menarini, Mylan, Sanofi, and Sanofi Regeneron, and has served as a consultant for or received honoraria from Akcea, Amgen, Daiichi Sankyo, Esperion Therapeutics, Inc., Ionis Pharmaceuticals, Kowa, Medco, Menarini, Merck, Mylan, Novartis, Recordati, Regeneron, Sanofi, The Corpus, and Viatris. UL has received research grants or funding from Amgen, Daiichi Sankyo, Novartis, and Sanofi. GBJM received research grant(s)/support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, HLS Therapeutics, Merck, Novo Nordisk, and Sanofi, and has served as a consultant for these companies as well as Esperion Therapeutics, Inc., Novartis, and Servier. KKR has received institutional research grant(s)/support from Amgen, MSD, Pfizer, Regeneron, and Sanofi, and served as a consultant for or received honoraria from AbbVie, Akcea, Algorithm, Amgen, AstraZeneca, Boehringer Ingelheim, Cerenis, Cipla, Dr Reddy's Laboratories, Lilly, Esperion Therapeutics, Inc., Kowa, Medco, MSD, Novo Nordisk, Pfizer, Regeneron, Resverlogix, Sanofi, Takeda, and Zuellig Pharma. CB is an employee of Esperion Therapeutics, Inc., and may own Esperion stock and/or stock options. YZ was an employee of Esperion Therapeutics, Inc. when the analysis was carried out and may hold stock and/or stock options. LL is a consultant contracted by Esperion Therapeutics, Inc. and may own Esperion stock or stock options. ACG has received research grant(s)/support from Amarin, Amgen, Akcea/IONIS, Arrowhead, Esperion Therapeutics, Inc., Merck, NewAmsterdam Pharma, Novartis, Pfizer, Regeneron, and Sanofi; has served as a consultant for 23andMe, Akcea, Esperion, IONIS, Merck, NewAmsterdam Pharma, Novartis, OptumRX, Regeneron, and Sanofi; and has provided editorial work for Merck.
(Copyright © 2024. Published by Elsevier Inc.)