Is Repatha (evolocumab) indicated for children with heterozygous familial hypercholesterolemia?

From the Guidelines

Repatha (evolocumab) is not recommended for children with heterozygous familial hypercholesterolemia (HeFH) based on the provided evidence, as the guidelines suggest traditional cholesterol-lowering therapies like statins as the first line of treatment 1. The guidelines recommend that children with HeFH should first try traditional cholesterol-lowering therapies like statins, and baseline LDL-C levels should be documented before considering other treatments 1. The recommended approach for managing hyperlipidemia in children involves a step-wise approach, starting with lifestyle modifications and then adding medications like statins or bile acid sequestrants if necessary 1. While Repatha (evolocumab) is approved for the treatment of HeFH in adults, its use in children is not explicitly recommended in the provided guidelines, and the decision to use it should be made on a case-by-case basis in consultation with a lipid specialist 1. Regular monitoring of lipid levels is crucial to assess treatment efficacy, and the choice of medication should be based on the individual child's needs and medical history 1. In general, the treatment of HeFH in children should focus on reducing the risk of cardiovascular disease and improving quality of life, while also considering the potential risks and benefits of different treatment options 1. Key considerations in the management of HeFH in children include the severity of the condition, the presence of other cardiovascular risk factors, and the potential impact of treatment on the child's quality of life 1. Ultimately, the decision to use Repatha (evolocumab) or any other medication for the treatment of HeFH in children should be made in consultation with a lipid specialist and based on the most up-to-date evidence and guidelines 1.

From the FDA Drug Label

The safety and effectiveness of REPATHA as an adjunct to diet and other LDL-C-lowering therapies for the treatment of HeFH have been established in pediatric patients aged 10 years and older. Use of REPATHA for this indication is based on data from a 24-week, randomized, placebo-controlled, double-blind trial in pediatric patients with HeFH In the trial, 104 patients received REPATHA 420 mg subcutaneously once monthly and 53 patients received placebo; 39 patients (25%) were 10 to 11 years of age

Repatha is indicated for children with heterozygous familial hypercholesterolemia (HeFH) aged 10 years and older.

• The safety and effectiveness of Repatha for this indication is supported by a 24-week clinical trial in pediatric patients with HeFH.
• Patients as young as 10 years old were included in the trial, with 25% of patients being between 10-11 years old. 2

From the Research

Repatha (Evolocumab) for Children with Heterozygous Familial Hypercholesterolemia

• Repatha, a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9, has been shown to be effective in lowering low-density lipoprotein (LDL) cholesterol levels in adult patients 3.
• A 24-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of evolocumab in pediatric patients with heterozygous familial hypercholesterolemia, demonstrating a mean percent change from baseline in LDL cholesterol level of -44.5% in the evolocumab group and -6.2% in the placebo group 4.
• The results of this trial suggest that evolocumab can reduce LDL cholesterol levels and other lipid variables in pediatric patients with familial hypercholesterolemia, with an incidence of adverse events similar to that of the placebo group 4.

Safety and Efficacy of Repatha in Children

• The long-term safety and efficacy of evolocumab in patients with homozygous familial hypercholesterolemia and severe heterozygous familial hypercholesterolemia have been evaluated in an open-label, single-arm study, with results showing that evolocumab was well tolerated and effectively reduced plasma LDL-C levels over a median of 4.1 years 5.
• The study found that adverse events occurred in 89.3% of patients, with the most common being nasopharyngitis, influenza, upper respiratory tract infection, and headache, and that the adjudicated cardiovascular event rate was 2.7% per year 5.
• The efficacy and safety of statins, which are often used in combination with evolocumab, have also been evaluated in children with heterozygous familial hypercholesterolemia, with results showing that statins can reduce LDL cholesterol levels and are generally well tolerated, although long-term safety remains unknown 6, 7.

Treatment Goals and Outcomes

• The goal of treatment for children with heterozygous familial hypercholesterolemia is to reduce LDL cholesterol levels to <3.5 mmol/L (130 mg/dL), with a meta-analysis of 41 studies finding that lipid-lowering therapy can significantly reduce LDL cholesterol levels, although achieving treatment goals can be challenging 7.
• The meta-analysis found that only 38.7% of children achieved the LDL cholesterol goal, and that large differences in treatment outcomes existed between countries, highlighting the need for early combination therapy and individualized treatment approaches 7.