Background and Aims

To assess the efficacy and safety of lomitapide in paediatric patients with homozygous familial hypercholesterolaemia (HoFH).

Methods

APH-19 (NCT04681170) is an ongoing phase 3, open-label, single-arm trial of lomitapide in paediatric patients with HoFH receiving standard-of-care lipid-lowering therapy. The study consisted of a run-in period, followed by a 24-week efficacy phase, 80-week safety phase and follow-up period. Patients were stratified by age into three dose escalation groups: 5–10, 11– 15 and 16–17 years, where maximum daily doses were 20, 40 and 60 mg, respectively. Patients were titrated to maximum tolerated doses from a starting dose of 2 mg (patients 5–15 years) or 5 mg (16–17 years).

Results

Forty-three patients were treated (Female: 55.8%; mean age: 10.7 years). APH-19 met its primary endpoint; mean change from baseline LDL-C at Week 24 was -53.5% (95% CI -61.6 – -45.4, p<0.0001), with results similar between patients aged 5–10 and 11–17 (Figure 1). Mean reductions were also observed at Week 24 for non-high-density lipoprotein C (-53.9%; 95% CI -61.7 – -46.1, p<0.0001), total cholesterol (-50.1%; 95% CI -57.6 – -42.5, p<0.0001) and very-low-density lipoprotein cholesterol (-50.2%; 95% CI -59.1 – -41.2, p<0.0001).

Patients reported mild (48.8%), moderate (30.2%) and severe (11.6%) adverse events (AEs). One patient experienced a life-threatening AE (MACE; treatment unrelated). No serious AEs led to discontinuation.

Conclusions

In this study, lomitapide significantly reduced LDL-C levels in paediatric HoFH patients. Safety was consistent with the known profile of lomitapide, with no new signals identified.

Figure 1: Mean (SD) change from baseline LDL-C (mg/dL) Week 24