EU expands label for Chiesi’s Lojuxta to children with ultra-rare cholesterol disorder

Edited by Robert McTiernan··2 min read

The European Commission has approved an expanded indication for Italy-based Chiesi’s Lojuxta (lomitapide) to include children aged 5 years and older with homozygous familial hypercholesterolaemia (HoFH). The decision extends use of a therapy that has been available to adult patients in the EU since 2013. For a condition where cardiovascular damage can begin in early childhood, the decision marks the first EU-approved oral agent for pediatric HoFH, addressing a population that has historically been managed with limited systemic pharmacological options.

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) previously issued a positive opinion for the label expansion, which covers lomitapide capsules as an adjunct to a low-fat diet, exercise, and other lipid-lowering treatments, including LDL-apheresis where available. Genetic confirmation of HoFH is required whenever possible, and secondary causes of hypercholesterolaemia must be excluded before initiating treatment.

Lomitapide inhibits microsomal triglyceride transfer protein (MTP), a hepatic enzyme essential for assembling very-low-density lipoprotein (VLDL) particles. By blocking this step, the drug reduces the production and secretion of both VLDL and LDL, lowering circulating LDL-cholesterol through a mechanism that operates independently of LDL receptor function — a critical distinction in HoFH, where receptor-mediated LDL clearance is severely impaired or absent.

The EC decision was based on data from APH-19, a Phase III, open-label, single-arm, multicentre study enrolling 43 paediatric participants aged 5 to 17 years with HoFH. The primary endpoint was mean percentage change in LDL-cholesterol from baseline at week 24. The study reported a mean 53.5% reduction in LDL-C from baseline at week 24 (p < 0.0001), with statistically significant reductions also observed in non-HDL-C, total cholesterol, VLDL-C, apolipoprotein B, and triglycerides. Adverse events were predominantly mild and consistent with lomitapide's established profile in adults, including gastrointestinal and hepatic effects. One serious treatment-emergent adverse event — an elevation in hepatic enzymes — resulted in dose interruptions and reductions in a single patient.

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Lomitapide’s LDL receptor-independent mechanism is particularly relevant in HoFH, where biallelic mutations in the LDLR gene render conventional PCSK9-targeting agents largely ineffective. Unlike PCSK9 inhibitors, which depend on functional LDL receptors to clear circulating LDL, lomitapide acts upstream by reducing hepatic lipoprotein production.

The most direct approved comparator in the same paediatric HoFH indication is Evkeeza (evinacumab), Regeneron’s anti-ANGPTL3 monoclonal antibody, which received EC approval for children aged 5 years and older with HoFH. Evinacumab also operates independently of LDL receptor function and is administered intravenously. Lomitapide’s oral formulation offers a mechanistically distinct, self-administered alternative, though its hepatic enzyme monitoring requirements and gastrointestinal tolerability profile introduce practical considerations for long-term pediatric use.

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