High levels of
low-density lipoprotein cholesterol (
LDL-C) and
lipoprotein(a) [Lp(a)] are associated with early morbidity and mortality caused by
cardiovascular disease (CVD). There are hints that a reduction of
LDL-C levels beyond currently advocated targets, and the use of drugs that also have Lp(a)-lowering potential, could provide further clinical benefit. Today,
LDL apheresis is the only available treatment option to achieve further lowering of
apolipoprotein-B (
apo-B)-containing
lipoproteins, especially Lp(a).
Mipomersen is currently being studied in patients with mild to severe hypercholesterolaemia as add-on
therapy to other
lipid-lowering
therapy, as monotherapy in patients who are intolerant of
HMG-CoA reductase inhibitors (
statins) and who are at high risk for CVD. Patients affected by homozygous or heterozygous familial hypercholesterolaemia (FH), which are inherited autosomal co-dominant disorders characterized by a marked elevation of serum
LDL-C concentration, remain a clinical challenge, especially when their CVD risk is aggravated by additionally elevated Lp(a) levels.
Mipomersen is a 20-mer
oligonucleotide [2'-O-(2-methoxy) ethyl-modified
oligonucleotide], a second-generation
antisense oligonucleotide (AOS), complementary to the coding region for human-specific
apo-B-100 messenger RNA (
mRNA).
Mipomersen inhibits
apo-B-100 synthesis and is consequently a new treatment strategy to lower
apo-B-containing
lipoproteins like
LDL-C and Lp(a) in patients at high risk for CVD not on target or intolerant to
statins. This article focuses on
mipomersen and gives an overview of the current status of
mipomersen as a promising treatment option. Recent studies have shown a decrease in
LDL-C levels of 22-42.2% and in Lp(a) of 19.6-31.1% from baseline, depending on study design. Dose-dependent reductions of
very low-density lipoprotein cholesterol (VLDL-C) and
triglyceride levels have also been observed. Although the short-term efficacy and safety of
mipomersen have been proven, side effects like
injection-site reactions (up to 90-100%), increased liver
enzymes,
cephalgias,
nasopharyngitis,
myalgia,
nausea and
fatigue must be mentioned and critically discussed. Furthermore, we need more data on the long-term side effects, especially regarding the long-term potential for hepatic steatosis. Data on cardiovascular outcomes with
mipomersen are also not yet available.