Lomitapide in paediatric patients with HoFH: the APH-19 study

Familial hypercholesterolaemia (FH) is the most common autosomal-dominant genetic disorder marked by lifelong elevations of low-density lipoprotein cholesterol (LDL C).¹ Two FH subtypes occur, with homozygous familial hypercholesterolaemia (HoFH) the more rare and severe.² Without treatment, most patients with elevated LDL C levels resulting from HoFH develop overt atherosclerosis before the age of 20 years,³ and mean life expectancy is approximately 18 years.⁴ Patients develop progressive cardiovascular disease over time and remain at very high cardiovascular risk despite the best standard of care lipid-lowering treatment.⁵ In Europe, first-line therapy is high-intensity statin and ezetimibe ± PCSK9-directed therapy within 8 weeks.⁶ However, most patients require additional therapies including lomitapide, evinacumab or lipoprotein apheresis.⁶ Lomitapide is a microsomal triglyceride transfer protein inhibitor that effectively lowers serum LDL C independent of LDL receptor function⁷ and is currently approved only for the treatment of adults.⁶ The efficacy and safety of lomitapide in paediatric patients with HoFH receiving standard-of-care lipid-lowering therapy has been investigated recently in the open-label, single-arm, Phase III APH-19 trial.⁸ Results from APH-19 show lomitapide has the potential to be an effective and safe LDL-independent early treatment option for paediatric patients with HoFH.⁸

• Understand the mechanisms of disease that drive the pathology of HoFH and the mechanism of action of lomitapdide
• Discuss the key challenges of managing paediatric patients with HoFH, and how the objectives and design of the APH-19 study aimed to address these unmet needs
• Recall and describe key efficacy and safety outcomes of the APH-19 study, and the implications of these results for clinical practice