Evinacumab for Pediatric Homozygous Familial Hypercholesterolemia

Quick Takes

  • Evinacumab, an angiopoietin-like 3 inhibitor, is now approved by the FDA as an adjunct to other lipid-lowering therapies to treat patients 5-11 years of age with homozygous familial hypercholesterolemia.
  • Evinacumab treatment decreased LDL-C with significant reductions starting in the first week.
  • Reductions in apoB, non–HDL-C, and total cholesterol were observed as well.

Study Questions:

What is the efficacy and safety of evinacumab in pediatric patients with homozygous familial hypercholesterolemia (HoFH)?


The investigators conducted a phase 3 open-label single-arm study, which included 14 patients, 5-11 years of age, with genetically proven HoFH (true homozygotes and compound heterozygotes) and low-density lipoprotein cholesterol (LDL-C) levels >130 mg/dL, despite optimized lipid-lowering therapy (including LDL receptor [LDLR]-independent apheresis and lomitapide). Participants were recruited from 10 sites across Australia, Austria, the Netherlands, Taiwan, Ukraine, and the United States. Participants were treated with intravenous evinacumab 15 mg/kg every 4 weeks for 24 weeks. The primary efficacy objective for part B was to quantify the mean percent change in LDL-C with evinacumab from baseline to week 24. Secondary objectives for part B included the effect of evinacumab on lipid and lipoprotein levels. The safety and tolerability of evinacumab were also assessed.


A total of 14 participants were included in part B of the study; mean age was 9.5 (standard deviation 5.11) years, and 57.1% were girls. At baseline, 7 of 14 patients (50%) were receiving lipoprotein apheresis, and all 14 patients were also receiving other nonstatin lipid-lowering therapies. LDLR genotyping showed that most patients were compound heterozygous (71.4%) and belonged to the defective/defective, defective/negative, as well as negative/negative LDLR variant categories. Evinacumab treatment decreased LDL-C with reduction starting in the first week, with a mean (standard error [SE]) LDL-C reduction of −48.3% (SE 10.4%) from baseline to week 24. Reductions in apolipoprotein B (APOB), non–high-density lipoprotein cholesterol, and total cholesterol were observed as well: (mean [SE], –41.3% [9.0%]) for ApoB, (–48.9% [9.8%]) for non–HDL-C, and (–49.1% [8.1%]) for total cholesterol. Treatment-emergent adverse events were reported in 10 (71.4%) patients; however, only two (14.3%) reported events that were considered to be treatment-related (nausea and abdominal pain). One serious treatment-emergent adverse event of tonsillitis occurred (n = 1), but this was not considered treatment-related.


The authors conclude that evinacumab constitutes a new treatment for pediatric patients with HoFH and inadequately controlled LDL-C despite optimized lipid-lowering therapy, lowering LDL-C levels by nearly half in these extremely high-risk and difficult-to-treat individuals.


This phase 3 open-label study suggests that evinacumab is an effective treatment for pediatric patients with HoFH. Although these data should be supported in larger trials, the current trial supports the US Food and Drug Administration (FDA) approval of evinacumab.

Clinical Topics: Dyslipidemia, Homozygous Familial Hypercholesterolemia, Prevention

Keywords: Atherosclerosis, Hypercholesterolemia, Pediatrics

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