Evinacumab and reduced lipoprotein apheresis in pediatric homozygous familial hypercholesterolemia: a retrospective study on LDL-C.

BACKGROUND AND AIMS: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by severely elevated low-density lipoprotein cholesterol (LDL-C) from birth, leading to accelerated atherosclerotic cardiovascular disease and premature death if untreated. Evinacumab, a monoclonal antibody targeting angiopoietin-like 3 (ANGPTL3), offers an LDL receptor-independent pathway to lower LDL-C. This study aimed to evaluate the effect of evinacumab on lipid levels and its potential to reduce lipoprotein apheresis (LA) frequency in children and adolescents with HoFH.

METHODS: This was a single-center, retrospective, observational study of six patients aged 10-19 years who had genetically confirmed HoFH and were treated with stable doses of lipid-lowering therapy (LLT) and evinacumab with or without LA at the Medical University of Vienna. Demographic characteristics, lipid levels, and treatment details were collected.

RESULTS: At the first visit, LDL-C levels ranged from 521 to 870 mg/dL (13.5-22.5 mmol/L). With stable LLT plus LA, pre-LA LDL-C levels were reduced to 212-352 mg/dL (5.5-9.1 mmol/L) and, after evinacumab was added, further reductions to 90-201 mg/dL (2.3-5.2 mmol/L) were observed. However, during periods of reduced LA frequency, pre-LA LDL-C levels increased to 105-216 mg/dL (2.7-5.6 mmol/L), exceeding the target of 115 mg/dL (3.0 mmol/L) in three out of four patients. LA frequency reduction from weekly to three times per month was only possible in one patient, but no patients had termination of LA.

CONCLUSIONS: Evinacumab effectively lowers LDL-C in children and adolescents with HoFH. However, its ability to facilitate long-term reduction in LA frequency was not shown and remains unclear.