Mipomersen and its use in familial hypercholesterolemia

ABSTRACT

Introduction: 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.

KEYWORDS:

• Antisense oligonucleotide
• familial hypercholesterolemia
• lomitapide
• mipomersen

Acknowledgments

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Diabetes And Digestive And Kidney Diseases or the National Institutes of Health.

Declaration of interest

AC Goldberg has received clinical trial grants via her medical school from Genzyme, ISIS, IONIS, Merck & Co, Pfizer Inc, Amgen Inc, Regeneron, Sanofi/Regeneron, GlaxoSmithKline, Amarin Corporation, The Medicines Company and Genentech. She has also received honoraria for consultancy and/or serving on the advisory boards of Sanofi/Regeneron, Optum Rx, Esperion and uniQure. Furthermore, AC Goldberg has also received modest honoraria for editorial work for Merck & Co working with them on a manual. She also has board and committee memberships and has received speaker’s fees from the National Lipid Association, and has received speaker fees from the Endocrine Society. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Referee disclosures

One referee declares having received honoraria from Sanofi and Akcea.

Additional information

Funding

JS Parham has received support from the National Institute of Diabetes and Digestive and Kidney Diseases via award number [T32DK007120].