Alirocumab reduces LDL-C in paediatric HeFH

Alirocumab administered every 2 or 4 weeks (Q2W or Q4W) significantly reduced low-density lipoprotein-cholesterol (LDL-C) levels in paediatric patients with heterozygous familial hypercholesterolaemia (HeFH), according to a study presented at ESC 2023.

HeFH is characterized by an elevated level of LDL-C and is associated with early-onset atherosclerotic cardiovascular disease. [J Am Coll Cardiol 2018;72:662-680]

“Statins and other lipid-lowering therapies are prescribed in children aged 8–10 years to reduce lipid concentrations to recommended targets. However, alternative therapies are needed for patients who cannot achieve LDL-C targets with statins or who are statin intolerant,” said lead author Dr Raul Santos from the University of São Paulo, Brazil.

This phase III trial analysed 153 paediatric patients aged 8–17 years with HeFH inadequately controlled with statin therapy. Participants were randomized to receive either alirocumab (Q2W cohort: n=49 and Q4W cohort: n=52) or placebo (Q2W cohort: n=25 and Q4W cohort: n=27) during a 24-week double-blind treatment period. Dosing was initiated based on body weight: <50 kg (40 mg for Q2W or 150 mg for Q4W) and ≥50 kg (75 mg for Q2W or 300 mg for Q4W).

Double-blind treatment period

At week 24, alirocumab significantly reduced LDL-C levels by 33.6 percent with Q2W dosing and 38.2 percent with Q4W dosing. With placebo, LDL-C levels were increased by 9.7 percent and decreased by 4.4 percent, respectively.

The treatment difference between alirocumab and placebo in mean LDL-C percent change from baseline to week 24 was -43.3 percent in the Q2W cohort and -33.8 percent in the Q4W cohort (p<0.0001 for both).

With regard to other lipid parameters, such as apolipoprotein B, non-HDL-C*, total cholesterol, and lipoprotein(a), significant treatment differences favouring alirocumab Q2W and Q4W dosing over placebo were observed at week 24, noted Santos.

Open-label treatment period

Upon completion of the double-blind treatment period, 145 participants entered the open-label treatment period and were treated with alirocumab Q2W (n=71) or Q4W (n=74) for an additional 80 weeks.

LDL-C levels were reduced by 26.3 percent and 23.8 percent with alirocumab Q2W and Q4W, respectively. Santos pointed out that the reductions in LDL-C levels with alirocumab were sustained through week 104.

In terms of safety, no significant difference in adverse events (AEs) was observed between the alirocumab and placebo groups during both treatment periods.

Only two patients in the alirocumab Q4W cohort discontinued treatment due to AEs whereas none in the Q2W cohort.

“Overall, both dosing regimens of alirocumab were associated with significant reductions in LDL-C and other proatherogenic lipid parameter concentrations in paediatric patients with HeFH,” said Santos.

The safety and tolerability profile of alirocumab for paediatric patients was favourable. “Alirocumab represents a promising adjunct therapy to statins for paediatric patients with uncontrolled HeFH,” he added.