Introduction: The Unmet Medical Need in Homozygous Familial Hypercholesterolaemia
Homozygous familial hypercholesterolaemia (HoFH) represents one of the most challenging phenotypes in clinical lipidology. Characterized by a near-complete lack of low-density lipoprotein receptor (LDLR) activity, patients with HoFH experience extreme elevations in LDL cholesterol (LDL-C), often exceeding 13 mmol/L (500 mg/dL) from birth. This leads to accelerated atherosclerosis, with cardiovascular events frequently occurring in the first or second decade of life. While conventional therapies such as statins, ezetimibe, and PCSK9 inhibitors have revolutionized the management of heterozygous FH, their efficacy is severely limited in HoFH because they rely primarily on the upregulation of functional LDLRs. Consequently, there is a critical need for therapies that lower LDL-C through mechanisms independent of the LDL receptor pathway.
