The effects of mipomersen, a second-generation antisense oligonucleotide, on atherogenic (apoB-containing) lipoproteins in the treatment of homozygous familial hypercholesterolemia

Mipomersen (Kynamro (R) [mipomersen sodium injection]; Genzyme, a Sanofi Company, MA, USA) is indicated as an adjunct to lipid-lowering medications and diet to reduce LDL-C, apoB, total cholesterol and non-HDL cholesterol in patients with homozygous familial hypercholesterolemia. In a 6-month Phase III trial (n = 51), mean percent change in LDL-C was -25% (95% CI: -32 to -18) versus placebo -3% (95% CI: -12 to 5; p < 0.001). The absolute mean LDL-C reduction was 113 mg/dl (2.92 mmol/l). Lipoprotein(a) was also significantly lowered by -31% (95% CI: -39 to -23) versus placebo -8% (95% CI: -19 to 3; p < 0.01). Some patients experienced transient and generally reversible hepatic effects, mild-to-moderate injection site reactions and flu-like symptoms. The mechanism of action and metabolism of mipomersen makes drug-drug interactions unlikely.