The 91st European Atherosclerosis Society (EAS) Congress took place from May 21-24, 2023. During the Congress, many stakeholders discussed the latest developments in basic, translational, and clinical research into vascular disease, as well as clinical updates and treatment/diagnosis guidelines. As shared in Medscape, one presentation focused on a Phase 3 study which evaluated lomitapide for pediatric homozygous familial hypercholesterolemia (HoFH). Learn more about lomitapide.

Early diagnosis and treatment is crucial for people living with HoFH. According to one of the presenters, HoFH comes with a life expectancy of just 18 years in untreated patients. While there are some therapies available for HoFH, many of them are strictly used in adults and have yet to be tested extensively in pediatric populations. 

Study Findings

In this Phase 3 study, researchers sought to determine whether lomitapide—which was approved 11 years ago for adults with HoFH—was similarly effective for children with this condition. Altogether, 43 participants (ages 5 to 17) enrolled in the study. In addition to being given nutritional supplements and a low-fat diet, participants received varying lomitapide doses over a 24-week period. They were then all escalated to the maximum tolerated dose for an 80-week safety period. The study findings show that:

• 41.9% (18 participants) reached a cholesterol target of <135 mg/dL during the initial treatment period. 
• Lomitapide treatment significantly lowered LDL cholesterol levels, with an overall reduction of 53.5% seen throughout the study. 
• Besides LDL cholesterol reductions, lomitapide also reduced non-HDL and very-low-density lipoprotein cholesterol levels by over 50% respectively. 
• Children ages 5-10 saw slightly more LDL cholesterol reduction than older groups. 

While lomitapide was effective in reducing LDL cholesterol levels, only 7% of participants did not experience side effects. 11.6% (5 participants) had severe reactions and two participants discontinued lomitapide use due to safety issues. Side effects included gastrointestinal distress, heightened liver enzymes, and a cardiac event. Some researchers suggest that more research is needed to determine whether this drug’s safety profile is adequate for pediatric populations. 

What is Homozygous Familial Hypercholesterolemia (HoFH)? 

There are two types of familial hypercholesterolemia, a rare and inherited form of high cholesterol: homozygous and heterozygous. Homozygous familial hypercholesterolemia (HoFH) is rarer and more severe than its counterpart. An estimated 1 in every 300,000 people globally has HoFH. APOB and PCSK9 gene mutations have been implicated in HoFH development, though other genes may also play a role. These mutations prevent LDL receptors from removing low-density lipoprotein cholesterol (LDL cholesterol) from the blood. As a result, people with this condition may have LDL levels that are more than 4x the normal level. Outside of extremely high cholesterol, symptoms may include:

• Shortness of breath
• Chest pain
• White/gray circles on the cornea
• Xanthomas (yellow, waxy patches on the skin)
• Xanthelasmas (yellowish fat deposits under the skin)
• A swollen or painful Achilles tendon
• Rapid heartbeat
• Heart disease (complication) 

A number of treatment options are being explored in clinical studies. When it comes to the current standards-of-care, PCSK9 inhibitors, lomitapide, and LDL-apheresis may be used.