Report on Mipomersen (Kynamro): A Comprehensive Monograph

Introduction: Mipomersen and the Advent of Antisense Oligonucleotide Therapy for Hypercholesterolemia

Mipomersen, marketed under the trade name Kynamro, represents a pioneering therapeutic agent in the class of antisense oligonucleotides (ASOs), specifically engineered as an inhibitor of apolipoprotein B-100 (ApoB-100) synthesis.[1] Its development and subsequent regulatory review marked a significant milestone in medicine, as it became the first systemically administered ASO to gain approval from the U.S. Food and Drug Administration (FDA) for a chronic lipid disorder.[3]

The drug was developed to address a profound unmet medical need in patients with homozygous familial hypercholesterolemia (HoFH), a rare, severe, and life-threatening genetic disorder. HoFH is characterized by extremely high levels of low-density lipoprotein cholesterol (LDL-C) from birth, leading to aggressive and premature atherosclerotic cardiovascular disease (ASCVD).[2] Patients with HoFH often exhibit a limited or negligible response to conventional lipid-lowering therapies, such as statins, because the underlying pathology involves defective or absent LDL-receptor function, which is the primary target of statin therapy.[5] Mipomersen offered a novel therapeutic strategy by providing an LDL-receptor-independent mechanism to lower the burden of atherogenic lipoproteins.[7] The development of Mipomersen signified a strategic evolution in therapeutic design, moving beyond the modulation of existing biological pathways toward directly silencing the genetic source code of a key pathogenic protein. This approach bypasses the inherent limitations of traditional therapies in HoFH patients by targeting the mRNA blueprint for ApoB-100 before the protein is synthesized, representing a foundational step toward precision medicine for severe genetic dyslipidemias.