Mipomersen

Mipomersen is an antisense oligonucleotide designed to target apolipoprotein B-100 (apoB-100) mRNA in the liver. By binding to apoB-100 mRNA, mipomersen promotes RNase H–mediated degradation, reducing hepatic production of apoB-100 and thereby decreasing very-low-density lipoprotein (VLDL) assembly and lowering low-density lipoprotein cholesterol (LDL-C).

Indications and status: In the United States, mipomersen is approved for adults with homozygous familial hypercholesterolemia (HoFH) as an adjunct to diet and other lipid-lowering therapies to reduce LDL-C. A pediatric indication exists for patients aged 12 years and older with HoFH who have not achieved sufficient LDL-C reduction with other therapies, depending on regulatory labeling. The drug is available under a restricted program due to safety concerns.

Administration and dosing: Mipomersen is given by subcutaneous injection once weekly. The typical dose is 200 mg per week. Dosing and duration are guided by clinical response and safety monitoring.

Safety and monitoring: A key safety concern is potential liver injury, including hepatic steatosis and elevations in transaminases. Because of these risks, mipomersen is available only through a restricted program with required liver-related monitoring. Baseline and periodic liver function tests are recommended, and discontinuation may be necessary if significant liver injury or hepatic steatosis occurs. Common adverse effects include injection-site reactions and flu-like symptoms, along with fatigue, nausea, and headaches. Use is generally avoided in pregnancy and in individuals with significant hepatic impairment.

Pharmacology and overview: Mipomersen is a phosphorothioate-modified antisense oligonucleotide with liver-selective activity, reflecting its primary role in lowering hepatic apoB-100 production and downstream LDL-C through reduced VLDL synthesis.