Safety and effectiveness of evinacumab in an infant with homozygous familial hypercholesterolemia: A new renaissance for the very young?

Abstract

The rare homozygous form of familial hypercholesterolemia (HoFH) is characterized by extremely high low-density lipoprotein (LDL) cholesterol levels, typically exceeding 13 mmol/L (500 mg/dL), and a variable phenotype that may include marked premature atherosclerotic cardiovascular disease. HoFH with null-null LDL receptor mutations can be highly resistant to standard pharmacological therapies. The standard of care treatment option is lipoprotein apheresis (LA). However, LA is not commonly available, is technically demanding, and is relatively invasive and arduous for very young patients. Here we report effective lowering of the LDL cholesterol in a 13-month-old child with HoFH treated with evinacumab, initially at a low dose (7.5 mg/kg), later increased to 15 mg/kg/28 days. The decision was made after the failure of standard drug therapies in a sibling with the same null-null mutation in the LDL receptor, submitted to liver transplantation, who had severe complications. The treatment with evinacumab was safe and effective; LDL cholesterol, triglycerides, and apolipoprotein B concentrations all decreased by over 80%. Our findings suggest that evinacumab is a safe and effective option for treating very young patients with HoFH who do not respond to conventional therapies.