Mipomersen and other therapies for the treatment of severe familial hypercholesterolemia

Figures & data

Figure 1 Discrete clinical manifestations of familial hypercholesterolemia. (A) Corneal arcus and xanthelasma; (B) extensor tendon xanthomas; (C and D) Achilles tendon xanthomas.

Note: Copyright © 2008, The Australian Association of Clinical Biochemists. Reproduced with permission from Burnett JR, Hooper AJ. Common and rare gene variants affecting plasma LDL cholesterol. Clin Biochem Rev. 2008;29(1):11–26.⁶⁸

Figure 2 Cumulative LDL exposure (expressed as grams of cholesterol per year) over a lifetime in familial hypercholesterolemia patients (HeFH, HoFH) and normal individuals.

Note: Coronary heart disease occurs after a theoretical threshold of LDL exposure is exceeded, reached in early childhood in HoFH and early middle-age in HeFH.^27,69 Copyright © 2009, The American Society for Biochemistry and Molecular Biology. Adapted with permission from Horton JD, Cohen JC, Hobbs HH. PCSK9: a convertase that coordinates LDL catabolism. J Lipid Res. 2009;50 Suppl:S172–S177.⁶⁹
Abbreviations: CHD, coronary heart disease; HeFH, heterozygous familial hypercholesterolemia; HoFH, homozygous familial hypercholesterolemia; LDL, low-density lipoprotein.

Table 1 Effects of mipomersen on plasma apoB, LDL-cholesterol, triglyceride, HDL-cholesterol, and Lp(a) in FH

Study	Patient population	Duration	Mipomersen dose (mg/week)	Baseline LDL-C (mmol/L)	% change from baseline
					ApoB	LDL-C	TG	HDL-C	Lp(a)
Akdim et al^Citation61	Heterozygous FH, n = 44	6 weeks	0	4.42 ± 1.2	−1	0	−16	8	−3
			50	5.35 ± 2.0	−10	−13	6	−1	−3
			100	4.50 ± 1.0	−8	−11	6	−3	−15
			200	4.24 ± 0.8	−23*	−21*	−23*	−1	−17
			300	4.50 ± 0.9	−33*	−34*	−22*	6	−24
Raal et al^Citation65	Homozygous FH, n = 51	26 weeks	0	10.4 ± 3.7	−2.5	−3.3	0.4	3.9	−7.9
			200	11.4 ± 3.6	−27*	−25*	−17*	15*	−31*
Visser et al^Citation66	Statin-intolerant patients, including FH, n = 33	26 weeks	0	6.3 ± 1.7	−4.3	−2.0	5.8	−2.2	0
			200	6.3 ± 2.4	−46*	−47*	−28*	8.1	−27*
Stein et al^Citation70 (abstract)	Heterozygous FH, n = 124	26 weeks	0	3.70	7	5	0.9	5.2	0
			200	3.96	−26*	−28*	−14*	3.1	−21*
Tardif et al^Citation71 (abstract)	Severe heterozygous FH, n = 58	26 weeks	0	6.44		13
			200	7.14		−36*

Note:

* P < 0.05.

Abbreviations: ApoB, apolipoprotein B; FH, familial hypercholesterolemia; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein (a); TG, triglyceride.

BurnettJRHooperAJCommon and rare gene variants affecting plasma LDL cholesterolClin Biochem Rev2008291112618566665

 PubMedGoogle Scholar

RaalFJSantosRDHomozygous familial hypercholesterolemia: Current perspectives on diagnosis and treatmentAtherosclerosis2012223226226822398274

 PubMed Web of Science ®Google Scholar

HortonJDCohenJCHobbsHHPCSK9: a convertase that coordinates LDL catabolismJ Lipid Res200950SupplS172S17719020338

 PubMed Web of Science ®Google Scholar

AkdimFVisserMETribbleDLEffect of mipomersen, an apolipoprotein B synthesis inhibitor, on low-density lipoprotein cholesterol in patients with familial hypercholesterolemiaAm J Cardiol2010105101413141920451687

 PubMed Web of Science ®Google Scholar

RaalFJSantosRDBlomDJMipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trialLancet20103759719998100620227758

 PubMed Web of Science ®Google Scholar

VisserMEWagenerGBakerBFMipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trialEur Heart J20123391142114922507979

 PubMed Web of Science ®Google Scholar

SteinEADufourRGagneCA randomized, double-blind, placebo-controlled study to assess efficacy and safety of mipomersen as add-on therapy in heterozygous familial hypercholesterolemia patients with coronary artery diseaseEur Heart J20103189820402003

 PubMed Web of Science ®Google Scholar

TardifJCMcGowanMCeskaRApolipoprotein B synthesis inhibition by mipomersen reduces low-density lipoprotein cholesterol when added to maximally tolerated lipid-lowering medication in patients with severe heterozygous hypercholesterolemiaJ Am Coll Cardiol20115714E492

 Web of Science ®Google Scholar