TY - JOUR
T1 - Bempedoic acid safety analysis
T2 - Pooled data from four phase 3 clinical trials
AU - Bays, Harold E.
AU - Banach, Maciej
AU - Catapano, Alberico L.
AU - Duell, P. Barton
AU - Gotto, Antonio M.
AU - Laufs, Ulrich
AU - Leiter, Lawrence A.
AU - Mancini, G. B.John
AU - Ray, Kausik K.
AU - Bloedon, Le Anne T.
AU - Sasiela, William J.
AU - Ye, Zhan
AU - Ballantyne, Christie M.
N1 - Funding Information:
The authors offer appreciation to all study investigators, clinical site staff, and study participants. K.K.R. acknowledges support from the NIHR Imperial Biomedical Research Centre. Amy Feng, of Esperion, provided additional statistical support and reviewed the manuscript for accuracy. Medical writing/editorial support (funded by Esperion) for preparation of this article was provided by Crystal Murcia, PhD, and Kelly M. Cameron, PhD, CMPP, of JB Ashtin.
Funding Information:
This work was financially supported by Esperion Therapeutics, Inc. Esperion was involved in the design of the studies, in collaboration with an expert steering committee, in the conduct of the studies, and in data collection and management. Esperion was involved in the analysis and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication but had no veto authority with respect to publication or control of the decision regarding choice of journal for submission.
Funding Information:
The authors offer appreciation to all study investigators, clinical site staff, and study participants. K.K.R. acknowledges support from the NIHR Imperial Biomedical Research Centre. Amy Feng, of Esperion, provided additional statistical support and reviewed the manuscript for accuracy. Medical writing/editorial support (funded by Esperion) for preparation of this article was provided by Crystal Murcia, PhD, and Kelly M. Cameron, PhD, CMPP, of JB Ashtin. This work was financially supported by Esperion Therapeutics, Inc. Esperion was involved in the design of the studies, in collaboration with an expert steering committee, in the conduct of the studies, and in data collection and management. Esperion was involved in the analysis and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication but had no veto authority with respect to publication or control of the decision regarding choice of journal for submission. The data, analytic methods, and study materials will not be made available to other researchers for purposes of reproducing the results or replicating the procedures. Authors' contributions: H.E.B. M.B. A.L.C. U.L. and K.K.R. were all involved in the concept/design of the manuscript and data interpretation. P.B.D. L.A.L. and G.B.J.M. were involved in the data interpretation. L.T.B. W.J.S. and C.M.B. were all involved in the concept/design of the manuscript, data acquisition, and data interpretation. Z.Y. was involved in the concept/design, data acquisition, statistical analysis, and data interpretation. All authors critically reviewed the manuscript and approved the final version of the manuscript for submission. Financial disclosure: H.E.B. has received research grants from 89Bio, Acasti, Akcea, Amarin, Amgen, AstraZeneca, Civi, Esperion, Evidera, Matinas, Merck, Novartis, Pfizer, Regeneron, and Sanofi; served as a consultant/advisor for 89Bio, Amarin, Esperion, and Matinas; and served as a speaker for Esperion. M.B. has received research grant(s)/support from Amgen, Sanofi, Valeant, and Mylan and has served as a consultant for Abbott/Mylan, Abbott Vascular, Actavis, Akcea, Amgen, Biofarm, KRKA, MSD, Sanofi-Aventis, Servier, Valeant, Freia Pharmaceuticals, Polfarmex, Daiichi Sankyo, Esperion, Lilly, and Resverlogix. A.L.C. has received research grant(s)/support from Sanofi, Sanofi Regeneron, Amgen, Mylan, and Menarini and has served as a consultant for Amgen, Sanofi, Esperion, Novartis, Ionis Pharmaceuticals, Mylan, Menarini, Recordati, and S.P.B.D. has received institutional research grant(s)/support from Retrophin, Regeneron, and Regenxbio and has served as a consultant for Akcea, AstraZeneca, Esperion, Retrophin, Regeneron, and Regenxbio. A.M.G., Jr. reported being an Esperion Therapeutics, Inc. board member, chairing the Akcea Therapeutics Data and Safety Monitoring Board, and receiving personal fees from Amarin Pharmaceuticals, Esperion Therapeutics, Inc., Ionic Pharmaceuticals, and Kowa Pharmaceuticals during the conduct of the study and outside the submitted work. U.L. has served as a consultant for Amgen, Esperion, and Sanofi. G.B.J.M. has received research grant(s)/support from Merck, AstraZeneca, Amgen, Sanofi, Novo Nordisk, and Boehringer Ingelheim and has served as a consultant for these companies as well as Esperion, Novartis, and Servier. L.A.L. has received research grant(s)/support from AstraZeneca, Amgen, Kowa, Novartis, The Medicines Company, and Sanofi/Regeneron. He has also served as a consultant for AstraZeneca, Amgen, Esperion, Merck, Novartis, The Medicines Company, and Sanofi/Regeneron. K.K.R. has received research grant(s)/support from Amgen, MSD, Pfizer, Regeneron, and Sanofi (all paid to his institution) and served as a consultant for or received honoraria from AbbVie, Akcea, Algorithm, Amgen, AstraZeneca, Boehringer Ingelheim, Cerenis, Cipla, Dr Reddy's Laboratories, Eli Lilly, Esperion, Kowa, Medco, MSD, Novo Nordisk, Pfizer, Regeneron, Resverlogix, Sanofi, Takeda, and Zuellig Pharma. L.T.B., W.J.S., and Z.Y. are employees of Esperion Therapeutics, Inc. and may hold stock and/or stock options. C.M.B. has received research grant(s)/support from Abbott Diagnostic, Akcea, Amarin, Amgen, Esperion, Ionis, Novartis, Regeneron, Roche Diagnostic, Sanofi-Synthelabo, the NIH, the AHA, and the ADA (all paid to his institution). He has also served as a consultant for Abbott Diagnostics, Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Esperion, Intercept, Ionis, Matinas BioPharma Inc, Merck, Novartis, Novo Nordisk, Regeneron, Roche Diagnostic, and Sanofi-Synthelabo.
Publisher Copyright:
© 2020 National Lipid Association
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Background: An ongoing need exists for safe and effective lipid-lowering therapies (LLTs) for patients unable to achieve desired lipid levels with current treatment options. Objective: The objective of this study was to describe the safety profile of bempedoic acid, an oral, first-in-class, adenosine triphosphate (ATP)–citrate lyase inhibitor that significantly reduces low-density lipoprotein cholesterol (LDL-C) levels by 17.4%–28.5% vs placebo. Methods: This was a pooled analysis of four phase 3, randomized (2:1), double-blind, placebo-controlled studies in patients with hypercholesterolemia who required additional LDL-C lowering, despite stable maximally-tolerated LLT. Patients received 180 mg of bempedoic acid (n = 2424) or placebo (n = 1197) once daily for 12 to 52 weeks. Assessments included treatment-emergent adverse events (TEAEs) and clinical laboratory tests. Results: Of 3621 patients (the median drug exposure: 363 days), exposure-adjusted TEAE rates were 87.1/100 and 82.9/100 person-years (PY) for bempedoic acid and placebo, respectively. No single TEAE influenced the difference in rates. TEAEs leading to discontinuation occurred at rates of 13.4/100 and 8.9/100 PY for bempedoic acid vs placebo, with the most common cause being myalgia, which occurred less frequently with bempedoic acid vs placebo (1.5/100 vs 2.0/100 PY). Rates of myalgia and muscle weakness were comparable vs placebo. Bempedoic acid was associated with mild increases in blood urea nitrogen, creatinine, and uric acid and decreases in hemoglobin. These laboratory abnormalities were apparent by week 4, stable over time, and reversible after treatment cessation. Gout incidence was 1.6/100 vs 0.5/100 PY in the bempedoic acid vs placebo groups. New-onset diabetes/hyperglycemia occurred less frequently with bempedoic acid vs placebo (4.7/100 vs 6.4/100 PY). The safety profile was consistent across subgroups. Conclusions: Bempedoic acid is generally safe and well tolerated among patients with hypercholesterolemia who require additional LLT.
AB - Background: An ongoing need exists for safe and effective lipid-lowering therapies (LLTs) for patients unable to achieve desired lipid levels with current treatment options. Objective: The objective of this study was to describe the safety profile of bempedoic acid, an oral, first-in-class, adenosine triphosphate (ATP)–citrate lyase inhibitor that significantly reduces low-density lipoprotein cholesterol (LDL-C) levels by 17.4%–28.5% vs placebo. Methods: This was a pooled analysis of four phase 3, randomized (2:1), double-blind, placebo-controlled studies in patients with hypercholesterolemia who required additional LDL-C lowering, despite stable maximally-tolerated LLT. Patients received 180 mg of bempedoic acid (n = 2424) or placebo (n = 1197) once daily for 12 to 52 weeks. Assessments included treatment-emergent adverse events (TEAEs) and clinical laboratory tests. Results: Of 3621 patients (the median drug exposure: 363 days), exposure-adjusted TEAE rates were 87.1/100 and 82.9/100 person-years (PY) for bempedoic acid and placebo, respectively. No single TEAE influenced the difference in rates. TEAEs leading to discontinuation occurred at rates of 13.4/100 and 8.9/100 PY for bempedoic acid vs placebo, with the most common cause being myalgia, which occurred less frequently with bempedoic acid vs placebo (1.5/100 vs 2.0/100 PY). Rates of myalgia and muscle weakness were comparable vs placebo. Bempedoic acid was associated with mild increases in blood urea nitrogen, creatinine, and uric acid and decreases in hemoglobin. These laboratory abnormalities were apparent by week 4, stable over time, and reversible after treatment cessation. Gout incidence was 1.6/100 vs 0.5/100 PY in the bempedoic acid vs placebo groups. New-onset diabetes/hyperglycemia occurred less frequently with bempedoic acid vs placebo (4.7/100 vs 6.4/100 PY). The safety profile was consistent across subgroups. Conclusions: Bempedoic acid is generally safe and well tolerated among patients with hypercholesterolemia who require additional LLT.
KW - ATP-Citrate lyase inhibitor
KW - Hypercholesterolemia
KW - Low-density lipoprotein cholesterol
KW - Statins
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U2 - 10.1016/j.jacl.2020.08.009
DO - 10.1016/j.jacl.2020.08.009
M3 - Article
C2 - 32980290
AN - SCOPUS:85091711598
SN - 1933-2874
VL - 14
SP - 649-659.e6
JO - Journal of Clinical Lipidology
JF - Journal of Clinical Lipidology
IS - 5
ER -