Table 3.

Summary of new lipid-lowering agents for the treatment of HoFH

LIPID-LOWERING AGENT	CHARACTERISTICS
	AVAILABILITY IN CANADA	MECHANISM	DOSING REGIMEN	MEAN LDL REDUCTION FROM BASELINE	CLINICAL OUTCOME EVIDENCE	CONTRAINDICATIONS	ADVERSE EFFECTS	POTENTIAL DRUG INTERACTIONS
	Lomitapide^*	Yes (approved February 4, 2014)	An MTP inhibitor that prevents assembly of VLDL thereby reducing LDL levels	5–60 mg orally once daily	38%–50%	None	Pregnancy; chronic bowel disease (eg, IBD, malabsorption); moderate or severe hepatic impairment; use of a moderate or strong CYP 3A4 inhibitor; coadministration with simvastatin ≥ 40 mg/d	Gastrointestinal intolerance, liver enzyme elevations, hepatic steatosis	Inhibits CYP 3A4 (eg, interacts with atorvastatin, lovastatin, simvastatin, warfarin) Inhibits P-glycoprotein (eg, interacts with colchicine, dabigatran, digoxin) CYP 3A4 substrate
Mipomersen^†	No	An antisense oligonucleotide targeted against Apo B mRNA, which prevents synthesis of Apo B thereby decreasing LDL levels	200 mg SC once weekly	25%	None	Moderate or severe hepatic impairment	Injection-site reaction, flulike symptoms, liver enzyme elevations, hepatic steatosis	None known
PCSK9 inhibitors (alirocumab, bococizumab, evolocumab)^‡	No	A PCSK9 inhibitor that prevents the breakdown of LDL receptors thereby enhancing LDL elimination	75–150 mg of alirocumab SC every 2 wk 150 mg of bococizumab SC every 2 wk 140 mg of evolocumab SC every 2 wk or 420 mg SC every 4 wk	48%–65% for HeFH; 23% for HoFH	None	None known	Injection-site reaction; musculoskeletal symptoms	None known

Apo B—apolipoprotein B, CYP 3A4—cytochrome P450 enzyme subtype 3A4, HeFH—heterozygous familial hypercholesterolemia, HoFH—homozygous familial hypercholesterolemia, IBD—inflammatory bowel disease, LDL—low-density lipoprotein, mRNA—messenger ribonucleic acid, MTP—microsomal triglyceride transfer protein, PCSK9—proprotein convertase subtilisin-kexin type 9, SC—subcutaneously, VLDL—very low–density lipoprotein.
↵* Data for lomitapide characteristics from Rader and Kastelein,³² Aegerion Pharmaceuticals,³³ and Cuchel et al.³⁴
↵† Data for mipomersen characteristics from Rader and Kastelein,³² Genzyme,³⁵ Raal et al,³⁶ and Akdim et al.³⁷
↵‡ Data for characteristics of PCSK9 inhibitors from Navarese et al.³⁸