Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: Design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial

Journal of Clinical Lipidology

Volumn 8, Issue 6, 2014, Pages 554-561

  Moriarty, Patrick M ^a   Jacobson, Terry A ^b   Bruckert, Eric ^c   Thompson, Paul D ^d   Guyton, John R ^e   Baccara Dinet, Marie T ^f   Gipe, Daniel ^g  

^a UNIVERSITY OF KANSAS SCHOOL OF MEDICINE   (United States)

^b EMORY UNIVERSITY   (United States)

^c PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

^d HARTFORD HOSPITAL   (United States)

^e DUKE UNIVERSITY MEDICAL CENTER   (United States)

^f SANOFI   (France)

^g REGENERON PHARMACEUTICALS INC   (United States)

Author keywords

Alirocumab; Ezetimibe; Hypercholesterolemia; Muscle symptoms; PCSK9; Phase 3 clinical trial; Statin intolerance; Statin myopathy

Indexed keywords

ALIROCUMAB; ATORVASTATIN; EZETIMIBE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PLACEBO; AZETIDINE DERIVATIVE; HEPTANOIC ACID DERIVATIVE; MONOCLONAL ANTIBODY; PCSK9 PROTEIN, HUMAN; PYRROLE DERIVATIVE; SERINE PROTEINASE;

ADULT; ARTICLE; CARDIOVASCULAR RISK; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG HYPERSENSITIVITY; DRUG RECHALLENGE; DRUG SAFETY; FAMILIAL HYPERCHOLESTEROLEMIA; HUMAN; INTENTION TO TREAT ANALYSIS; MAJOR CLINICAL STUDY; MULTICENTER STUDY; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; TREATMENT DURATION; TREATMENT OUTCOME; TREATMENT RESPONSE; BLOOD; CANADA; CARDIOVASCULAR DISEASES; CLINICAL TRIAL; DOSE CALCULATION; EUROPE; IMMUNOLOGY; IMMUNOTHERAPY; MYALGIA; PROCEDURES; RISK; UNITED STATES;

ANTIBODIES, MONOCLONAL; AZETIDINES; CANADA; CARDIOVASCULAR DISEASES; CHOLESTEROL, LDL; DRUG DOSAGE CALCULATIONS; EUROPE; HEPTANOIC ACIDS; HUMANS; IMMUNOTHERAPY; MYALGIA; PROPROTEIN CONVERTASES; PYRROLES; RISK; SERINE ENDOPEPTIDASES; UNITED STATES;

EID: 84923845326     PISSN: 19332874     EISSN: 18764789     Source Type: Journal    
DOI: 10.1016/j.jacl.2014.09.007     Document Type: Article

References (38)

1. N.J. Stone, J. Robinson, A.H. Lichtenstein, and et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines J Am Coll Cardiol 63 2013 2889 2934
2. G.B. Mancini, A.Y. Tashakkor, S. Baker, and et al. Diagnosis, prevention, and management of statin adverse effects and intolerance: Canadian Working Group Consensus update Can J Cardiol 29 2013 1553 1568
3. R.S. Rosenson, S.K. Baker, T.A. Jacobson, S.L. Kopecky, and B.A. Parker An assessment by the Statin Muscle Safety Task Force: 2014 update J Clin Lipidol 8 2014 S58 S71
4. M.Y. Wei, M.K. Ito, J.D. Cohen, E.A. Brinton, and T.A. Jacobson Predictors of statin adherence, switching, and discontinuation in the USAGE survey: understanding the use of statins in America and gaps in patient education J Clin Lipidol 7 2013 472 483
5. E. Bruckert, G. Hayem, S. Dejager, C. Yau, and B. Begaud Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients-the PRIMO study Cardiovasc Drugs Ther 19 2005 403 414
6. J.D. Cohen, E.A. Brinton, M.K. Ito, and T.A. Jacobson Understanding Statin Use in America and Gaps in Patient Education (USAGE): an internet-based survey of 10,138 current and former statin users J Clin Lipidol 6 2012 208 215
7. W.M. Mampuya, D. Frid, M. Rocco, and et al. Treatment strategies in patients with statin intolerance: the Cleveland Clinic experience Am Heart J 166 2013 597 603
8. H.V. Ganga, H.B. Slim, and P.D. Thompson A Systematic Review of Statin-Induced Muscle Problems in Clinical Trials Am Heart J 168 2014 6 15
9. B.A. Parker, J.A. Capizzi, A.S. Grimaldi, and et al. Effect of statins on skeletal muscle function Circulation 127 2013 96 103
10. M. Farnier PCSK9 inhibitors Curr Opin Lipidol 24 2013 251 258
11. E.A. Stein, and F.J. Raal Insights into PCSK9, low-density lipoprotein receptor, and low-density lipoprotein cholesterol metabolism: of mice and man Circulation 127 2013 2372 2374
12. J.M. McKenney, M.J. Koren, D.J. Kereiakes, C. Hanotin, A.C. Ferrand, and E.A. Stein Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy J Am Coll Cardiol 59 2012 2344 2353
13. E.M. Roth, J.M. McKenney, C. Hanotin, G. Asset, and E.A. Stein Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia N Engl J Med 367 2012 1891 1900
14. E.A. Stein, D. Gipe, J. Bergeron, and et al. Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised controlled trial Lancet 380 2012 29 36
15. E.M. Roth, M.R. Taskinen, H.N. Ginsberg, and et al. Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: Results of a 24week, double-blind, randomized Phase 3 trial Int J Cardiol 176 2014 55 61
16. J.R. Guyton, H.E. Bays, S.M. Grundy, and T.A. Jacobson An assessment by the Statin Intolerance Panel: 2014 update J Clin Lipidol 8 2014 S72 S81
17. E. Stroes, D. Colquhoun, D. Sullivan, and et al. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab J Am Coll Cardiol 63 2014 2541 2548
18. D. Sullivan, A.G. Olsson, R. Scott, and et al. Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial JAMA 308 2012 2497 2506
19. National Institute for Health and Clinical Excellence Identification and management of familial hypercholesterolemia. Guideline CG71 2008 Available at: http://publications.nice.org.uk/identification-and-management-of-familial-hypercholesterolaemia-cg71. Accessed February 3, 2014
20. World Health Organization Familial hypercholesterolaemia (FH): Report of a second WHO consultation 1999 Available at: http://whqlibdoc.who.int/hq/1999/WHO-HGN-FH-CONS-99.2.pdf. Accessed February 3, 2014
21. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report Circulation 106 2002 3143 3421
22. Z. Reiner, A.L. Catapano, B.G. De, and et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) Eur Heart J 32 2011 1769 1818
23. W.T. Friedewald, R.I. Levy, and D.S. Fredrickson Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge Clin Chem 18 1972 499 502
24. Food and Drug Administration Drug Approval Package. Zetia (ezetimibe) tablets 2014 Available at: http://www.accessdata.fda.gov/drugsatfda-docs/nda/2002/21445-Zetia.cfm. Accessed March 5, 2014
25. National Research Council The Prevention and Treatment of Missing Data in Clinical Trials 2010 The National Academies Press Washington, DC
26. O. Siddiqui, H.M. Hung, and R. O'Neill MMRM vs. LOCF: a comprehensive comparison based on simulation study and 25 NDA datasets J Biopharm Stat 19 2009 227 246
27. R.H. Eckel Approach to the patient who is intolerant of statin therapy J Clin Endocrinol Metab 95 2010 2015 2022
28. A.J. Keating, K.B. Campbell, and J.R. Guyton Intermittent nondaily dosing strategies in patients with previous statin-induced myopathy Ann Pharmacother 47 2013 398 404
29. S.P. Kennedy, G.P. Barnas, M.J. Schmidt, M.S. Glisczinski, and A.C. Paniagua Efficacy and tolerability of once-weekly rosuvastatin in patients with previous statin intolerance J Clin Lipidol 5 2011 308 315
30. H.E. Bays, M.H. Davidson, R. Massaad, and et al. Safety and efficacy of ezetimibe added on to rosuvastatin 5 or 10 mg versus up-titration of rosuvastatin in patients with hypercholesterolemia (the ACTE Study) Am J Cardiol 108 2011 523 530
31. J.J. Kastelein, F. Akdim, E.S. Stroes, and et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia N Engl J Med 358 2008 1431 1443
32. R.H. Knopp, H. Gitter, T. Truitt, and et al. Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia Eur Heart J 24 2003 729 741
33. J. Armitage The safety of statins in clinical practice Lancet 370 2007 1781 1790
34. M.H. Davidson, and J.G. Robinson Safety of aggressive lipid management J Am Coll Cardiol 49 2007 1753 1762
35. Food and Drug Administration FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury 2011 Available at: http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm. Accessed April 30, 2014
36. J. Perk, B.G. De, H. Gohlke, and et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts) Atherosclerosis 223 2012 1 68
37. D.R. Boyd, and S.J. Genuis The environmental burden of disease in Canada: respiratory disease, cardiovascular disease, cancer, and congenital affliction Environ Res 106 2008 240 249
38. V.L. Roger, A.S. Go, D.M. Lloyd-Jones, and et al. Heart disease and stroke statistics-2012 update: a report from the American Heart Association Circulation 125 2012 e2 e220