Lomitapide lowers LDL-C levels in paediatric homozygous familial hypercholesterolaemia

Children with homozygous familial hypercholesterolaemia (HoFH) achieve significant and clinically meaningful reductions in low-density lipoprotein cholesterol (LDL-C) with the microsomal triglyceride transfer protein (MTP) inhibitor lomitapide, which represents an efficient LDL receptor-independent treatment option, according to the open-label phase III APH-19 trial.

APH-19 enrolled 43 patients (median age 10.7 years, 56 percent female) with HoFH and on stable lipid-lowering therapy from 12 study centres across Germany, Israel, Italy, Saudi Arabia, Spain, and Tunisia. All patients underwent a 6-week run-in period, followed by a 24-week efficacy phase and an 80-week safety phase. Oral lomitapide was given initially at 2 mg for patients aged 5–15 years or 5 mg for patients aged 16–17 years, and then titrated to maximum tolerated doses.

The primary endpoint of the percentage change from baseline to week 24 in LDL-C was evaluated in patients who had received at least one dose of lomitapide and who had a baseline and at least one postbaseline measurement. Secondary endpoints included the percentage change from baseline at week 24 in total cholesterol, nonhigh-density lipoprotein cholesterol (non-HDL-C), very (V)LDL-C, apolipoprotein B, triglycerides, and lipoprotein(a). All patients who received at least one dose of study drug underwent the safety assessment.

At week 24, LDL-C decreased significantly by a mean of 53.5 percent (95 percent confidence interval, –61.6 to –45.4; p<0.0001). Significant reductions were also observed for non-HDL-C (mean, –53.9 percent; p<0.0001), total cholesterol (mean, –50.0 percent; p<0.0001), VLDL-C (mean, –50.2 percent; p<0.0001), apolipoprotein B (mean, –52.4 percent, p<0.0001), triglycerides (mean, –49.9 percent; p<0.0001), and lipoprotein(a) (mean, –11.3 percent in 21 patients with measurements in mg/dL; mean, –23.6 percent in 22 patients with measurements in nmol/L; p=0.0070 combined).

In terms of safety, adverse events were generally mild, with most being gastrointestinal and hepatic in nature. Adverse events of special interest occurred in five (12 percent) patients (gastrointestinal in two patients and hepatic in three). One serious treatment-emergent adverse event was recorded, specifically an elevation in hepatic enzymes that resulted in two dose interruptions, two dose reductions, and a repeated dose escalation.