Efficacy and safety of mipomersen sodium (Kynamro)

Expert Opinion on Drug Safety

Volumn 12, Issue 4, 2013, Pages 569-579

  Hovingh, Kees ^a   Besseling, Joost ^a   Kastelein, John ^b  

^a ACADEMIC MEDICAL CENTER   (Netherlands)

^b UNIVERSITY OF AMSTERDAM   (Netherlands)

Author keywords

Antisense; Apolipoprotein B; Familial hypercholesterolemia; Lipid lowering agent; Mipomersen

Indexed keywords

APOLIPOPROTEIN B; ATORVASTATIN; C REACTIVE PROTEIN; COMPLEMENT COMPONENT C3; EZETIMIBE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MIPOMERSEN; PLACEBO; SIMVASTATIN; TRIACYLGLYCEROL; WARFARIN;

BASAL CELL CARCINOMA; CARDIOVASCULAR RISK; CHOLESTEROL BLOOD LEVEL; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG INDUCED CANCER; DRUG SAFETY; DRUG STABILITY; DRUG STRUCTURE; DRUG TISSUE LEVEL; DRUG WITHDRAWAL; FAMILIAL HYPERCHOLESTEROLEMIA; FATIGUE; FATTY LIVER; FLU LIKE SYNDROME; HUMAN; IMMUNOGENICITY; INJECTION SITE ERYTHEMA; INJECTION SITE PAIN; LIPID METABOLISM; LIVER TOXICITY; MONOTHERAPY; REVIEW; SIDE EFFECT;

ANIMALS; ANTICHOLESTEREMIC AGENTS; HUMANS; HYPERLIPOPROTEINEMIA TYPE II; OLIGONUCLEOTIDES;

EID: 84878955971     PISSN: 14740338     EISSN: 1744764X     Source Type: Journal    
DOI: 10.1517/14740338.2013.793670     Document Type: Review

References (59)

1. Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment. Atherosclerosis 2012;223:262-8
2. van der Graaf A, Avis HJ, Kusters DM, et al. Molecular basis of autosomal dominant hypercholesterolemia: assessment in a large cohort of hypercholesterolemic children. Circulation 2011;123:1167-73
3. Soutar AK, Naoumova RP. Mechanisms of disease: genetic causes of familial hypercholesterolemia. Nat Clin Pract Cardiovasc Med 2007;4:214-25 (Pubitemid 46502094)
4. Rader DJ, Cohen J, Hobbs HH. Monogenic hypercholesterolemia: new insights in pathogenesis and treatment. J Clin Invest 2003;111:1795-803 (Pubitemid 38057721)
5. Goldstein JL, Hobbs HH, Brown MS. Familial hypercholesterolemia. In: Scriver CS, et al. editors. The metabolic and molecular bases of Inherited disease. 8th edition. McGraw-Hill Book Co; New York: 2001. p. 2863-913
6. Raal FJ, Pilcher GJ, Panz VR, et al. Reduction in mortality in subjects with homozygous familial hypercholesterolemia associated with advances in lipid-lowering therapy. Circulation 2011;124:2202-7
7. Graham I, Atar D, Borch-Johnsen K, et al. European guidelines on cardiovascular disease prevention in clinical practice: executive summary: Fourth 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). Eur Heart J 2007;28:2375-414 (Pubitemid 47542237)
8. Grundy SM, Cleeman JI, Merz CNB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation 2004;110:227-39 (Pubitemid 38924592)
9. Sjouke B, Kusters DM, Kastelein JJ, Hovingh GK. Familial hypercholesterolemia: present and future management. Curr Cardiol Rep 2011;13:527-36
10. Huijgen R, Kindt I, Verhoeven SB, et al. Two years after molecular diagnosis of familial hypercholesterolemia: majority on cholesterol-lowering treatment but a minority reaches treatment goal. PLoS ONE 2010;5:e9220
11. Thompson GR, Catapano A, Saheb S, et al. Severe hypercholesterolaemia: therapeutic goals and eligibility criteria for LDL apheresis in Europe. Curr Opin Lipidol 2010;21:492-8
12. Thompson GR. Recommendations for the use of LDL apheresis. Atherosclerosis 2008;198:247-55
13. Mabuchi H, Koizumi J, Shimizu M, et al. Long-term efficacy of low-density lipoprotein apheresis on coronary heart disease in familial hypercholesterolemia. Am J Cardiol 1998;82:1489-95 (Pubitemid 29006472)
14. Robinson JG, Goldberg AC; National Lipid Association Expert Panel on Familial Hypercholesterolemia. Treatment of adults with familial hypercholesterolemia and evidence for treatment: recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol 2011;5:S18-29
15. Merki E, Graham MJ, Mullick AE, et al. Antisense oligonucleotide directed to human apolipoprotein B-100 reduces lipoprotein(a) levels and oxidized phospholipids on human apolipoprotein B-100 particles in lipoprotein(a) transgenic mice. Circulation 2008;118:743-53
16. Crooke R, Baker B, Wedel M. Cardiovascular therapeutic applications. In: Crooke ST, editor. Antisense drug technology; principles, strategies and applications. 2nd edition. CRC Press; Boca Raton, Florida: 2007. p. 601-39
17. Kastelein JJ, Wedel MK, Baker BF, et al. Potent reduction of apolipoprotein B and low-density lipoprotein cholesterol by short-term administration of an antisense inhibitor of apolipoprotein B. Circulation 2006;114:1729-35 (Pubitemid 44607121)
18. Bennett CF, Swayze EE. RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu Rev Pharmacol Toxicol 2010;50:259-93
19. Yu RZ, Kim TW, Hong A, et al. Cross-species pharmacokinetic comparison from mouse to man of a second-generation antisense oligonucleotide, ISIS 301012, targeting human apolipoprotein B-100. Drug Metab Dispos 2007;35:460-8 (Pubitemid 46333910)
20. Yu RZ, Geary RS, Flaim JD, et al. Lack of pharmacokinetic interaction of mipomersen sodium (ISIS 301012), a 2¢-O-methoxyethyl modified antisense oligonucleotide targeting apolipoprotein B-100 messenger RNA, with simvastatin and ezetimibe. Clin Pharmacokinet 2009;48:39-50
21. Akdim F, Tribble DL, Flaim JD, et al. Efficacy of apolipoprotein B synthesis inhibition in subjects with mild-to-moderate hyperlipidaemia. Eur Heart J 2011;32:2650-9
22. Akdim F, Stroes ES, Sijbrands EJ, et al. Efficacy and safety of mipomersen, an antisense inhibitor of apolipoprotein B, in hypercholesterolemic subjects receiving stable statin therapy. J Am Coll Cardiol 2010;55:1611-18
23. Akdim F, Visser ME, Tribble DL, et al. Effect of mipomersen, an apolipoprotein B synthesis inhibitor, on low-density lipoprotein cholesterol in patients with familial hypercholesterolemia. Am J Cardiol 2010;105:1413-19
24. Yu RZ, Lemonidis KM, Graham MJ, et al. Cross-species comparison of in vivo PK/PD relationships for second-generation antisense oligonucleotides targeting apolipoprotein B-100. Biochem Pharmacol 2009;77:910-19
25. Product label approved by the US. Food and Drug Association on 1/29/2013 for Kynamro, NDA no.203568. Available from: http://www.accessdata.fda.gov/ drugsatfda-docs/label/2013/203568s000lbl.pdf [Last accessed 21 February 2013]
26. Raal FJ, Santos RD, Blom DJ, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet 2010;375:998-1006
27. McGowan MP, Tardif JC, Ceska R, et al. Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy. PLoS One 2012;7:e49006
28. Stein EA, Dufour R, Gagne C, et al. Apolipoprotein B synthesis inhibition with mipomersen in heterozygous familial hypercholesterolemia: results of a randomized, double-blind, placebo-controlled trial to assess efficacy and safety as add-on therapy in patients with coronary artery disease. Circulation 2012;126:2283-92
29. Visser ME, Wagener G, Baker BF, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, lowers LDL cholesterol in high risk-statin intolerant patients: a randomized, double-blind, placebo-controlled trial. Eur Heart J 2012;33:1142-9
30. Mipomersen sodium NDA 203568: Sponsor's briefing document for the Endocrinologic and Metabolic Drugs Advisory Committee scheduled for 18 October 2012. Available from: http://www.fda.gov/downloads/AdvisoryCommittees/Committees MeetingMaterials/Drugs/EndocrinologicandMetabolic DrugsAdvisoryCommittee/ UCM323931. pdf [Last accessed 29 November 2012]
31. Mipomersen Sodium. 2012. Available from: http://www.fda. gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ EndocrinologicandMetabolic DrugsAdvisoryCommittee/UCM325952. pdf [Last accessed 29 November 2012]
32. FDA Briefing Document, NDA 203568, Mipomersen Sodium Injection 200 mg/mL. Materials for the Endocrinologic and Metabolic Drugs Advisory Committee Meeting; 18 October 2012. Available from: http://www.fda.gov/downloads/ AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolic DrugsAdvisoryCommittee/UCM323927. pdf [Last accessed 1 March 2013]
33. Flaim JD, Hard M, Grundy J, et al. A phase 1 study in healthy volunteers to evaluate the pharmacokinetics, safety, and tolerability of mipomersen in 3 dosing regimens. Arteriosclerosis, Thrombosis, and Vascular Biology, 2011 Scientific Sessions (April 28-30 in Chicago, IL), abstract P138. Available from: http://my. americanheart.org/idc/groups/ahamahpublic/@ wcm/@sop/documents/ downloadable/ucm-428274.pdf [Last accessed 21 February 2013]
34. Furtado JD, Wedel MK, Sacks FM. Antisense inhibition of apoB synthesis with mipomersen reduces plasma apoC-III and apoC-III-containing lipoproteins. J Lipid Res 2012;53:784-91
35. Zheng C, Khoo C, Furtado J, Sacks FM. Apolipoprotein C-III and the metabolic basis for hypertriglyceridemia and the dense low-density lipoprotein phenotype. Circulation 2010;121:1722-34
36. Cromwell WC, Santos RD, Blom DJ, et al. Mipomersen, an apoB synthesis inhibitor, preferentially reduces small LDL particle number and increases LDL particle size in HoFH patients. Atherosclerosis Suppl 2010;11(2):107-8; P431
37. Lee RG, Fu W, Graham MJ, et al. Comparison of the pharmacological profiles of murine antisense oligonucleotides targeting apolipoprotein B and microsomal triglyceride transfer protein. J Lipid Res 2013;54:602-14
38. Tarugi P, Averna M, Di Leo E, et al. Molecular diagnosis of hypobetalipoproteinemia: an ENID review. Atherosclerosis 2007;195:e19-27 (Pubitemid 350087974)
39. Schonfeld G, Lin X, Yue P. Familial hypobetalipoproteinemia: genetics and metabolism. Cell Mol Life Sci 2005;62:1372-8 (Pubitemid 40853825)
40. Lonardo A, Lombardini S, Scaglioni F, et al. Hepatic steatosis and insulin resistance: does etiology make a difference? J Hepatol 2006;44:190-6
41. Schonfeld G, Patterson BW, Yablonskiy DA, et al. Fatty liver in familial hypobetalipoproteinemia: triglyceride assembly into VLDL particles is affected by the extent of hepatic steatosis. J Lipid Res 2003;44:470-8 (Pubitemid 37279694)
42. Visser ME, Lammers NM, Nederveen AJ, et al. Hepatic steatosis does not cause insulin resistance in people with familial hypobetalipoproteinaemia. Diabetologia 2011;54:2113-21
43. Amaro A, Fabbrini E, Kars M, et al. Dissociation between intrahepatic triglyceride content and insulin resistance in familial hypobetalipoproteinemia. Gastroenterology 2010;139(1):149-853
44. Ridker PM, Kastelein JJ, Genest J, Koenig W. C-reactive protein and cholesterol are equally strong predictors of cardiovascular risk and both are important for quality clinical care. Eur Heart J 2013; Epub ahead of print
45. Sampietro T, Bigazzi F, Rossi G, et al. Upregulation of the immune system in primary hypercholesterolaemia: effect of atorvastatin therapy. J Intern Med 2005;257:523-30 (Pubitemid 40776512)
46. Muscari A, Massarelli G, Bastagli L, et al. Relationship of serum C3 to fasting insulin, risk factors and previous ischaemic events in middle-aged men. Eur Heart J 2000;21:1081-90 (Pubitemid 30352992)
47. Bonovas S, Filioussi K, Tsavaris N, Sitaras NM. Statins and cancer risk: a literature-based meta-analysis and meta-regression analysis of 35 randomized controlled trials. J Clin Oncol 2006;24:4808-17 (Pubitemid 46655612)
48. Cholesterol Treatment Trialists' (CTT) Collaboration. Emberson JR, Kearney PM, Blackwell L, et al. Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy. PLoS One 2012;7(1):e29849
49. Kolansky DM, Curchel M, Clark BJ, et al. Longitudinal evaluation and assessment of cardiovascular disease in patients with homozygous familial hypercholesterolemia. Am J Cardiol 2008;102(11):1438-43
50. Raal FJ, Pilcher GJ, Waisberg R, et al. Low-density lipoprotein cholesterol bulk is the pivotal determinant of atherosclerosis in familial hypercholesterolemia. Am J Cardiol 1999;83:1330-3 (Pubitemid 29205741)
51. Ferrence BA, Wonsuk Y, Alesh I, et al. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a mendelian randomization analysis. J Am Coll Cardiol 2012;60:2631-9
52. Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005;366:1267-78
53. Robinson JG, Stone NJ. Identifying patients for aggressive cholesterol lowering: the risk curve concept. Am J Cardiol 2006;98:1405-8 (Pubitemid 44666653)
54. Versmissen J, Oosterveer DM, Yazdanpanah M, et al. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ 2008;337:a2423
55. Sniderman AD, Williams K, Contois JH, et al. A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes 2011;4(3):337-45
56. Barter PJ, Ballantyne CM, Carmena R, et al. Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirtyperson/ten-country panel. J Intern Med 2006;259(3):247-58
57. Grundy SM. Low-density lipoprotein, non-high-density lipoprotein, and apolipoprotein B as targets of lipid-lowering therapy. Circulation 2002;106:2526-9 (Pubitemid 35340685)
58. Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J 2010;31:2844-53
59. Thanassoulis G, Campbell CY, Owens DS, et al. CHARGE Extracoronary Calcium Working Group. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med 2013;368:503-12