Mipomersen and its use in familial hypercholesterolemia

Familial Hypercholesterolemia (FH) is an inherited disorder characterized by a defect in the binding and internalization of low-density lipoprotein (LDL) particles, resulting in markedly elevated LDL levels and premature atherosclerosis. It is one of the most common inherited disorders of lipid metabolism. Many FH patients, especially those with homozygous FH do not reach LDL goals with traditional LDL therapies and may require additional, less often used, therapies. Areas covered: Mipomersen is an anti-sense oligonucleotide that prevents production of apolipoprotein B leading to decreased levels of very low-density lipoprotein (VLDL) and LDL. In this review the authors discuss the pharmacokinetics of the drug, the clinical trials evaluating its efficacy and safety, and risks and challenges associated with its clinical implementation. Its use as therapy for the treatment of FH is also discussed. Expert opinion: Mipomersen is approved for use only in homozygous FH. It has frequent adverse effects, such as injection site reactions, flu-like symptoms, and hepatoxicity. It is useful only in patients who have failed other therapies, and it faces competition from other medications that have more tolerable side effect profiles.