Additional phase 3 results of MTP inhibitor in pediatric HoFH


EAS 2024 – Further analysis of the single-arm, dose-escalation APH-19 study among pediatric patients with homozygous familial hypercholesterolemia (HoFH) showed lomitapide reduced LDL-c (≤95%), apoB, and Lp(a) at 24 weeks. No safety concerns were observed.

This summary is based on the presentation of Lluis Masana, MD, PhD (Reus, Spain) at the EAS Congress 2024 - Lomitapide in paediatric patients with homozygous familial hypercholesterolaemia (HoFH) – analysis of patient-level LDL-c reduction, fat soluble vitamins, lipoproteins and patient maturation from APH-19 study.

Introduction and methods

Recently, the APH-19 study showed that 24-week treatment with lomitapide reduced LDL-c levels by 54% from baseline (P<0.0001) in pediatric patients with homozygous familial hypercholesterolemia (HoFH). Lomitapide is a microsomal triglyceride transfer protein (MTP) inhibitor with an LDL receptor–independent mechanism of action that has been approved for adults with HoFH by the FDA and EMA. The current analysis focused on additional parameters relating to the efficacy and safety of lomitapide in the same patient population.

The APH-19 study is an ongoing, international, multicenter, open-label, single-arm, dose-escalation, phase 3 study in which 46 HoFH patients aged 5–17 years who were on stable lipid-lowering therapy and a low-fat diet 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). This clinical trial comprises a 6- to 12-week run-in period, followed by a 24-week efficacy phase (n=43), an 80-week safety phase, and a follow-up period. Starting at week –2, participants received daily vitamin E supplementation.

In this additional analysis, patient-level LDL-c reductions, changes in lipoproteins (apoB and Lp(a)), and additional safety endpoints (growth/maturation and fat-soluble vitamin levels) at 24 weeks were assessed.

Main results

  • During the 24-week efficacy phase, 41.9% of the patients treated with lomitapide achieved the EAS-recommended LDL-c target (<135 mg/dL; <3.5 mmol/L).
  • In individual patients, lomitapide treatment resulted in LDL-c reductions from baseline to 24 weeks of up to 95%, with 23 patients (53.5%) showing an LDL-c reduction >50%.
  • The mean change in apoB levels from baseline to 24 weeks was –52.4% (P<0.0001). Subgroup analysis showed generally consistent results across subgroups stratified by age, concomitant medications, or history of CVD.
  • For Lp(a) measured in nmol/L, the mean change from baseline to 24 weeks was –23.6% (P=0.0030), whereas the mg/dL analysis indicated a mean change of –11.3% (P=0.2884). Combined analysis of the nmol/L and mg/dL measurements showed a significant Lp(a) reduction (Fisher’s combined P=0.0070).
  • There were no clinically significant mean changes in weight, height, or BMI (all adjusted for age) from baseline to 24 weeks.
  • Mean changes in vitamin A, vitamin D, and osteocalcin levels from baseline to 24 weeks were within the normal range for individuals aged 5–17 years.
  • At baseline, mean vitamin E levels were elevated (43.04 mg/L), but they were reduced by 25.72% at 24 weeks. Importantly, the mean vitamin E/total cholesterol ratio showed no significant difference between baseline and 24 weeks.


In this analysis of the open-label, single-arm, dose-escalation APH-19 study among pediatric HoFH patients, 24-week treatment with lomitapide resulted in reductions from baseline in levels of LDL-c (≤95%), apoB, and Lp(a). More than half of the patients had an LDL-c reduction >50%. There were no safety concerns, in particular no growth and maturation retardation or fat-soluble vitamin deficiency. Dr. Masana emphasized that longer-term data on lomitapide’s safety profile will become available in the next months.

- Our reporting is based on the information provided at the EAS Congress 2024 -

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