FDA Approves Lomitapide for Kids With Familial Hypercholesterolemia

The U.S. Food and Drug Administration (FDA) has approved the use of lomitapide (marketed as Juxtapid, by Chiesi Global Rare Diseases) for children as young as two years old with homozygous familial hypercholesterolemia (HoFH). This expands the existing approval, which previously covered only adult patients, offering a novel treatment option for a very rare and serious genetic condition impacting young people. The approval, announced on March 3, 2026, comes during Rare Disease Day, highlighting the importance of addressing conditions that affect slight populations.

Understanding Homozygous Familial Hypercholesterolemia

Homozygous familial hypercholesterolemia (HoFH) is a rare, inherited disorder that causes extremely high levels of low-density lipoprotein cholesterol (LDL-C) from birth. LDL-C, often referred to as “subpar” cholesterol, can build up in the arteries, leading to accelerated atherosclerosis – the hardening and narrowing of the arteries. Without intervention, individuals with HoFH face a significantly increased risk of heart disease and related complications at a young age. It’s estimated to affect roughly 1 in 250,000 to 1 in 360,000 people worldwide.

How Lomitapide Works

Lomitapide is a microsomal triglyceride transfer protein (MTP) inhibitor. This means it works by blocking the formation of chylomicrons and very low-density lipoprotein (VLDL), which are particles that carry cholesterol and other fats in the blood. By inhibiting their formation, lomitapide reduces the amount of LDL-C circulating in the bloodstream. It is designed to be used in conjunction with a low-fat diet, exercise, and other LDL-lowering therapies.

Evidence from the APH-19 Trial

The FDA’s decision to expand the approval of Juxtapid was based on data from the APH-19 trial (ClinicalTrials.gov Identifier: NCT04681170). This single-arm, open-label trial involved 43 pediatric patients aged 5 to 17 years with HoFH who were already following a low-fat diet and receiving other lipid-lowering treatments, including LDL apheresis where applicable. The trial was structured in three phases: a six-week run-in period, a 24-week efficacy assessment, and an 80-week safety follow-up.

During the efficacy phase, patients received lomitapide at an age-dependent starting dose, which was then adjusted to the maximum tolerated dose based on their age. The primary endpoint of the trial was the percentage change in LDL-C levels from the beginning of the study to week 24. Results showed a indicate reduction of 49% in LDL-C levels (95% Confidence Interval: -59% to -38%). Significant reductions were similarly observed in total cholesterol, apolipoprotein B, triglycerides, non-high-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol.

Trial Limitations and Considerations

It’s important to note that the APH-19 trial was a single-arm study, meaning there was no control group receiving a placebo or standard treatment. This limits the ability to definitively attribute the observed reductions in LDL-C solely to lomitapide. Even as the results are promising, further research, potentially including randomized controlled trials, may be needed to confirm these findings and assess the long-term effects of lomitapide in children with HoFH. The trial also included patients already receiving other lipid-lowering therapies, so the effect of lomitapide in patients not receiving these therapies is less clear.

What This Means for Families

Prior to this approval, managing HoFH in young children presented significant challenges. The expansion of Juxtapid’s approval offers a potentially valuable treatment option for children as young as two years old, allowing for earlier intervention and potentially reducing the long-term cardiovascular risks associated with this condition. Mitch Goldman, Senior Vice President of R&D at Chiesi Global Rare Diseases, emphasized that this approval is “a meaningful advancement for children and families living with HoFH,” enabling younger patients to benefit from a proven therapy.

Broader Context: Rare Disease Approvals and the FDA

This approval reflects a growing trend within the FDA to prioritize the development and approval of therapies for rare diseases. The Orphan Drug Act, passed in 1983, provides incentives for pharmaceutical companies to develop drugs for conditions affecting small patient populations. This has led to an increase in the number of orphan drugs approved in recent years, offering hope to individuals and families affected by these often-overlooked conditions.

Next Steps: Ongoing Monitoring and Research

With the approval now granted, the focus shifts to ongoing monitoring of the long-term safety and efficacy of lomitapide in pediatric patients. The APH-19 trial included an 80-week safety follow-up phase, and continued surveillance will be crucial to identify any potential adverse effects. Further research may also explore optimal dosing strategies and the potential for combining lomitapide with other emerging therapies for HoFH. Clinicians and families should stay informed about updates from the FDA and relevant medical societies regarding the use of lomitapide in children with this challenging condition.