Alirocumab Reduces LDL-C in Pediatric Heterozygous Familial Hypercholesterolemia

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Alirocumab every 2 or 4 weeks significantly reduced LDL-C in pediatric patients with inadequately controlled heterozygous familial hypercholesterolemia.

Alirocumab led to statistically significant reductions in low-density lipoprotein cholesterol (LDL-C) among pediatric patients with heterozygous familial hypercholesterolemia (HeFH) after 24 weeks of treatment.1

Results from a phase 3 randomized clinical trial suggested the treatment is an efficacious lipid-lowering therapy (LLT) among pediatric patients aged 8 to 17 years with HeFH inadequately controlled with statins undergoing every-2-week (Q2W) or every-4-week (Q4W) dosing.

“The efficacy of alirocumab reported here in pediatric patients with HeFH is generally consistent with that in adult patients, although the LDL-C reduction in the current study appeared to be lower than reductions previously reported in adults,” wrote the investigative team led by Raul D. Santos, MD, PhD, Lipid Clinic Heart Institute, University of Sao Paulo Medical School Hospital.

If left untreated, HeFH can lead to early-onset atherosclerotic cardiovascular disease (ASCVD), but better detection could prevent progression and premature CV events in adulthood. American College of Cardiology/American Heart Association (ACC/AHA) guidelines defined acceptable LDL-C concentrations in pediatric patients as <110 mg/dL and recommended statin initiation as young as eight years.2 However, many pediatric patients with HeFH are unable to attain recommended LDL-C concentrations with statins alone and require adjunct LLT.

A proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor, alirocumab has reduced LDL-C in adults with hyperlipidemia alone or combined with other LLTs. Results from a recent phase 2 dose-finding ODDYSEY KIDS study found alirocumab was well-tolerated and reduced LDL-C with results at higher doses among children with HeFH.3 These data supported the further investigation of alirocumab in pediatric HeFH.

The current phase 3 trial was conducted between May 2018 and August 2022 at 43 centers in 24 countries, with 40 centers randomized patients.1 Those aged 8 to 17 years were eligible if they had inadequately controlled HeFH despite statin treatment, with or without other LLTs, for ≥4 weeks. At randomization, patients were allocated 2:1 to Q2W or Q4W dosing cohorts to receive alirocumab or a matching placebo for 24 weeks in addition to their stable background LLT.

Treatment dosage depended on weight – the alirocumab dose was 40 mg for Q2W and 150 mg for Q4W if weight was <50 kg, or 75 mg for Q2W and 300 mg for Q4W if weight was ≥50 kg. A dose adjustment was performed at week 12 if the LDL-C was ≥110 mg/dL at week 8. After 24 weeks of double-blind treatment, the study sample could enter an open-label period to receive alirocumab and an LLT for up to 80 weeks.

Overall, 153 patients (mean age, 12.9 years; 87 [56.9%] female) were randomized (2:1) to receive alirocumab or placebo, following Q2W (n = 74) or Q4W dosing (n = 79). A total of 70 patients (95%) in the Q2W cohort and 75 (95%) in the Q4W cohort completed the double-blind treatment period.

Upon analysis, alirocumab was associated with a reduction in LDL-C from baseline at week 8 and maintained these reductions through week 24. The primary endpoint analysis revealed alirocumab significantly reduced LDL-C compared with placebo in both dosing cohorts, with a least-squares mean difference of –43.3% (97.5% CI, –56.0 to –30.7; P <.001) in the Q2W arm and –33.8% (97.5% CI, –46.4 to –21.2; P <.001) in the Q4W arm.

Further hierarchical analysis of the secondary efficacy endpoint exhibited significant improvements in other lipid parameters at weeks 12 and 24 with alirocumab treatment, including apo B, non-HDL-C, and total cholesterol. Reductions in LDL-C with alirocumab treatment remained well-maintained in the open-label period. Individuals who switched from placebo to alirocumab had reductions in LDL-C at week 32 maintained through week 104.

Safety data revealed two patients receiving alirocumab in the Q4W arm experienced adverse events leading to discontinuation, with no patient discontinuing alirocumab due to adverse events in the Q2W arm.

Otherwise, the analysis showed no significant differences in the incidence of adverse events between treatment groups. Santos and colleagues indicated these safety data remained generally consistent with expectations, owing to previous studies in pediatric and adult patients with HeFH.

“Alirocumab presents a suitable adjunct option to stable LLT in pediatric patients as young as 8 years old with HeFH,” they wrote.


  1. Santos RD, Wiegman A, Caprio S, et al. Alirocumab in Pediatric Patients With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial. JAMA Pediatr. Published online February 05, 2024. doi:10.1001/jamapediatrics.2023.6477
  2. GrundySM,StoneNJ,BaileyAL,etal.2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/ APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73(24):3168-3209. doi:10.1016/ j.jacc.2018.11.002
  3. Daniels S, Caprio S, Chaudhari U, et al. PCSK9 inhibition with alirocumab in pediatric patients with heterozygous familial hypercholesterolemia: The ODYSSEY KIDS study [published correction appears in J Clin Lipidol. 2020 Sep - Oct;14(5):741]. J Clin Lipidol. 2020;14(3):322-330.e5. doi:10.1016/j.jacl.2020.03.001