FDA Approves Lomitapide for Children With Homozygous Familial Hypercholesterolemia

The FDA has approved lomitapide (Juxtapid; Chiesi Global Rare Diseases) capsules for pediatric use in homozygous familial hypercholesterolemia (HoFH) for children aged 2 years and older. The approval expands the indication of lomitapide, which has been available for adults with HoFH in the United States since 2012, to include pediatric patients.¹

APH-19 Trial Results

The approval was based on results from APH-19, an open-label, single-arm phase 3 trial conducted at 12 study centers in Germany, Israel, Italy, Saudi Arabia, Spain, and Tunisia. Investigators enrolled 43 children and adolescents aged 5 to 17 years with HoFH who were receiving stable lipid-lowering therapy.²

The primary endpoint was percentage change from baseline to week 24 in low-density lipoprotein cholesterol (LDL-C). The mean change from baseline in LDL-C at week 24 was −53.5% (95% CI, −61.6 to −45.4; P < .0001). The trial also demonstrated significant reductions in non-high-density lipoprotein cholesterol (−53.9%), total cholesterol (−50.0%), very LDL cholesterol (−50.2%), apolipoprotein B (−52.4%), and triglycerides (−49.9%), with all changes showing P < .0001.²

Safety Profile

Adverse events in the APH-19 trial were mostly mild and primarily gastrointestinal and hepatic in nature. Adverse events of special interest were reported for 5 patients (12%): gastrointestinal in 2 patients and hepatic in 3 patients.²

One serious treatment-emergent adverse event was reported, classified as an adverse event of special interest: an increase in hepatic enzymes that resulted in 2 dose interruptions, 2 dose reductions, and a repeated dose escalation. No patients discontinued treatment due to adverse events during the 24-week efficacy phase.²

Mechanism of Action

Lomitapide is an orally administered microsomal triglyceride transfer protein (MTP) inhibitor that acts independently of the LDL receptor. The medication works by binding directly and selectively to MTP, thereby decreasing the assembly and secretion of apolipoprotein B-containing lipoproteins in both the liver and intestine. This receptor-independent mechanism makes lomitapide particularly valuable for HoFH patients who have little to no functional LDL receptor activity.^2-4

Understanding Homozygous Familial Hypercholesterolemia

HoFH is an ultra-rare, life-limiting genetic disorder. The condition impairs the function of the LDL receptor responsible for removing LDL-C from the body, resulting in extreme elevation of blood cholesterol levels. Untreated patients have a life expectancy of approximately 18 years.^1,3

Individuals with HoFH often develop premature and progressive atherosclerosis, a narrowing or blocking of the arteries. The loss of LDL receptor function results in severely elevated cholesterol levels that are often resistant to conventional lipid-lowering therapies.

Risk Evaluation and Mitigation Strategy

Lomitapide carries a boxed warning for the risk of hepatotoxicity. The medication is available only through the Juxtapid Risk Evaluation and Mitigation Strategy (REMS) program, which requires certification of all health care providers who prescribe lomitapide and all pharmacies that dispense the medication.^1,5

The REMS program aims to educate prescribers about the risk of hepatotoxicity and the need to monitor patients during treatment according to product labeling. It also ensures that access to therapy is restricted to patients with a clinical or laboratory diagnosis consistent with HoFH.⁵

Pharmacist Implications

Pharmacists play critical roles in supporting pediatric patients initiating lomitapide therapy. Key considerations include verification of REMS program enrollment for both prescribers and pharmacies before dispensing and counseling on proper dosage escalation schedules and the importance of adherence. Pharmacists are key to monitoring for hepatic adverse events and ensuring patients undergo required liver enzyme testing while ensuring coordination with prescribers regarding dose adjustments based on tolerability and liver enzyme levels.⁵

Drug interaction monitoring is essential, as lomitapide is metabolized by CYP3A4. Strong and moderate CYP3A4 inhibitors should not be used with lomitapide, and dosage should not exceed 30 mg daily when used concomitantly with weak CYP3A4 inhibitors. Doses of simvastatin (Zocor; Merck & Co.) or lovastatin (Mevacor; Merck & Co.) should be limited when co-administered with lomitapide due to increased risk of myopathy.¹

“Children with HoFH face extraordinary challenges from the moment they’re diagnosed,” Katherine Wilemon, founder and CEO of the Family Heart Foundation, said in the news release. “The recent treatment approval for this age group marks a meaningful step forward for young children impacted by HoFH.”¹

REFERENCES

1. Chiesi Global Rare Diseases announces FDA approval of Juxtapid (lomitapide) capsules for pediatric use in homozygous familial hypercholesterolemia (HoFH). News release. Chiesi Global Rare Diseases. Released March 3, 2026. Accessed March 3, 2026. https://chiesirarediseases.com/media/20251215chiesi-global-rare-diseases-announces-fda-approval-of-juxtapid-lomitapide-capsules-for-pediatric-use-in-homozygous-fa

2. Masana L, Zambon A, Schmitt CP, et al. Lomitapide for the treatment of paediatric patients with homozygous familial hypercholesterolaemia (APH-19): results from the efficacy phase of an open-label, multicentre, phase 3 study. Lancet Diabetes Endocrinol. 2024;12(12):880-889. doi:10.1016/S2213-8587(24)00233-X

3. Lomitapide shows promise in pediatric homozygous FH. Medscape. Published May 29, 2023. Accessed March 3, 2026. https://www.medscape.com/viewarticle/992523?form=fpf

4. Giammanco A, Cefalu AB, Noto D, Averna MR. Therapeutic options for homozygous familial hypercholesterolemia: the role of lomitapide. Curr Med Chem. 2020;27(23):3773-3783. doi:10.2174/0929867326666190121120735

5. FDA approved risk evaluation and mitigation strategies (REMS): lomitapide (Juxtapid). Accessed March 3, 2026. https://www.accessdata.fda.gov/scripts/cder/rems/