etc-1002 and gemcabene

Familial hypercholesterolemia (FH) is a common genetic condition characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C), premature atherosclerotic cardiovascular disease, and considerable unmet medical need with conventional LDL-C-lowering therapies. Between 2012 and 2015, the US Food and Drug Administration approved four novel LDL-C-lowering agents for use in patients with FH based on the pronounced LDL-C-lowering efficacy of these medicines. We review the four novel approved agents, as well as promising LDL-C-lowering agents in clinical development, with a focus on their mechanism of action, efficacy in FH cohorts, and safety.

Topics: Angiopoietin-like Proteins; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Benzimidazoles; Caproates; Cholesterol Ester Transfer Proteins; Dicarboxylic Acids; Fatty Acids; Genetic Therapy; Humans; Hyperlipoproteinemia Type II; Oligonucleotides; Receptors, LDL; RNA, Small Interfering; Treatment Outcome

Several new or emerging drugs for dyslipidemia owe their existence, in part, to human genetic evidence, such as observations in families with rare genetic disorders or in Mendelian randomization studies. Much effort has been directed to agents that reduce LDL (low-density lipoprotein) cholesterol, triglyceride, and Lp[a] (lipoprotein[a]), with some sustained programs on agents to raise HDL (high-density lipoprotein) cholesterol. Lomitapide, mipomersen, AAV8.TBG.hLDLR, inclisiran, bempedoic acid, and gemcabene primarily target LDL cholesterol. Alipogene tiparvovec, pradigastat, and volanesorsen primarily target elevated triglycerides, whereas evinacumab and IONIS-ANGPTL3-L

Topics: Antibodies, Monoclonal; Anticholesteremic Agents; Benzimidazoles; Caproates; Cholesterol, HDL; Cholesterol, LDL; Diacylglycerol O-Acyltransferase; Dicarboxylic Acids; Dyslipidemias; Ezetimibe; Fatty Acids; Genetic Therapy; Humans; Hypertriglyceridemia; Hypolipidemic Agents; Lipoprotein(a); Oligonucleotides; RNA, Small Interfering