Lunawati L. Bennett and Megan Chalk

Objective: To review the pharmacology and pharmacokinetics, and to evaluate the clinical efficacy, safety, and place in therapy of mipomersen sodium (Kynamro^®) for the treatment of familial hypercholesterolemia (FH).
Data Sources: A literature search through Pub Med and clinicaltrials.gov (1984–May 2014; English language) was performed using the key words: homozygous familial hypercholesterolemia (HoFH), heterozygous familial hypercholesterolemia (HeFH), FH, dyslipidemia, apolipoprotein B-100 (apoB-100), low density lipoprotein cholesterol (LDL-C), antisense oligonucleotides (ASOs), and ISIS 301012. Searches were limited to published studies in humans.
Study Selection and Data Extraction: All articles in English identified from reviews, abstracts, presentations, and clinical trials of mipomersen in humans were selected and included.
Data Synthesis: Mipomersen sodium (Kynamro^®), an oligonucleotide inhibitor of apoB-100 synthesis, is approved for reducing apoB-100, LDL-C, total cholesterol (TC), and non-high density lipoprotein cholesterol (non-HDL-C) in HoFH patients as an adjunctive treatment with other lipid lowering drugs and low fat diet.
Conclusion: Mipomersen is effective in decreasing LDL-C, apoB-100, TC, and non-HDL-C in patients that are refractory to other lipid lowering drugs. Mipomersen is administered as 200 mg subcutaneous (s.c.) once weekly injection. The drug is contraindicated in patients with moderate to severe hepatic impairment. The most common adverse reactions include injection site reaction (ISRs), influenza-like symptoms and increases in serum hepatic transaminase. Kynamro^® is only available through restricted program under Risk Evaluation and Mitigation Strategy (REMS) called Kynamro^® REMS.