Homozygous familial hypercholesterolemia, experience with Evinacumab treatment in two Mexican pediatric patients:...

Homozygous familial hypercholesterolemia (HoFH) is a rare and life-threatening genetic disorder characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C) levels from birth, leading to accelerated atherosclerotic cardiovascular disease and premature mortality. Conventional lipid-lowering therapies often provide insufficient LDL-C reduction, particularly in patients with minimal or absent LDL receptor (LDLR) function. Evinacumab, an angiopoietin-like protein 3 (ANGPTL3) inhibitor, lowers LDL-C independently of LDLR activity and represents a major therapeutic advance. Here we report two Mexican pediatric patients with HoFH who demonstrated profound LDL-C reductions following initiation of Evinacumab (59% and 68% within the first month of treatment), exceeding reductions observed in pivotal clinical trials. Both patients maintained sustained LDL-C reductions during long-term follow-up (up to 22 months). Importantly, temporary treatment interruption in both cases due to administrative and supply related difficulties limited access to Evinacumab was associated with marked rebound hypercholesterolemia. Reinitiation of therapy led to rapid and substantial lipid reduction, demonstrating a clear dechallenge-rechallenge effect and confirming the relevance of a continuous pharmacologic treatment with ANGPTL3 inhibition. Serial vascular imaging in one patient revealed partial regression of subclavian and carotid artery stenosis, as well as reduced aortic wall thickening following sustained LDL-C reduction; adding evidence to the recently described vascular improvement associated with Evinacumab therapy in pediatric HoFH. Both patients also experienced clinically meaningful improvements in quality of life, and treatment was well tolerated without serious adverse events.