Lomitapide in pediatric patients with HoFH

ESC 2026 – In a post-hoc analysis of APH-19 among pediatric patients with HoFH, treatment with lomitapide led to EAS 2023 LDL-c goal attainment in nearly half of the patients and reduced the need for apheresis.

This summary is based on the presentation of Alberto Zambon, MD, PhD (Padua, Italy) at the EAS 2026 - Long-term efficacy, tolerability, and safety of lomitapide in paediatric patients with homozygous familial hypercholesterolaemia (HoFH): post-hoc analyses of the APH-19 phase 3 clinical trial.

Introduction and methods

Homozygous familial hypercholesterolemia (HoFH) is characterized by elevated LDL-c levels from birth. Lomitapide is an oral microsomal triglyceride transfer protein (MTP) inhibitor approved by the FDA for lowering LDL-c levels in adult and pediatric patients with HoFH, and by the EMA for use in adults with HoFH. In the phase 3 APH-19 trial, lomitapide reduced LDL-c levels by 54% in pediatric patients with HoFH at week 24.

The aim of the current post-hoc analysis of APH-19 was to investigate the long-term safety and efficacy of lomitapide in pediatric patients with HoFH.

APH-19 was a phase 3, open-label trial that had a 24-week efficacy phase and an 80-week safety phase. Patients (age 5–17 years) were stratified by age into 3 lomitapide dose escalation groups (maximum doses: 20 mg for ages 5–10 years, 40 mg for ages 11–15 years, and 60 mg for ages 16–17 years). A total of 43 patients (mean age 11 years, 56% females) were included in the full and safety analysis set. Mean ± SD LDL-c level at baseline was 435.8 ± 189.5 mg/dL.

Main results

• The EAS 2014 LDL-c goal of <135 mg/dL was achieved by 53.5% of the patients at any time during follow-up up to week 104. 46.5% of the patients achieved the EAS 2023 LDL-c goal of <115 mg/dl.
• In patients with ASCVD (n=29), 31% of the patients achieved an LDL-c of <70 mg/dL at any time during follow-up up to week 104.
• Apheresis was reduced or discontinued at week 104 in 47.1% of patients who were on apheresis at week 24.
• Medication compliance was higher in patients aged 5–10 years compared with patients aged 11–17 years (95% vs. 70%), as was dietary compliance (85% vs. 62%).
• Gastrointestinal treatment-emergent adverse events were more frequent and longer-lasting in patients aged 16–17 years compared with younger patients.
• ALT/AST ratio ≥3x the upper limit of normal (ULN) were observed in 5 patients.
• Median increase in hepatic fat from baseline to week 104 was 3.6%.
• One patient experienced a hepatic fat level of 20% at week 24.

Conclusion

In this post-hoc analysis of APH-19 among pediatric patients with HoFH, treatment with lomitapide led to EAS 2023 LDL-c goal attainment in nearly half of the patients and reduced the need for apheresis. Safety results were consistent with the known safety profile of lomitapide.

- Our reporting is based on the information provided at the EAS 2026 -