Pediatric Drug Development Studies for Familial Hypercholesterolemia Submitted to the US Food and Drug Administration Between 2007–2020

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder of lipoprotein metabolism that leads to an increased risk of developing atherosclerosis and coronary artery disease. Hypercholesterolemia in pediatric patients is typically due to FH. Treatment of pediatric FH is achieved through lifestyle modifications, lipid-modifying pharmacotherapy, and/or apheresis. The primary objective of this review is to describe the characteristics of clinical trials conducted in pediatric patients with FH with data submitted to the US Food and Drug Administration (FDA) from 2007 to 2020. Out of 10 trials with 8 products in pediatric FH submitted to the FDA, 1 product was studied in both the heterozygous and the homozygous phenotypes, 5 were studied for heterozygous hypercholesterolemia (HeFH) only, and 2 were studied for homozygous familial hypercholesterolemia (HoFH) only. Most of the trials included pediatric patients 10 years of age and older. Clinical trial characteristics including the primary efficacy endpoints between pediatric and adult trials were mostly identical. Many lipid-lowering drugs with novel mechanisms of action have been recently approved or are currently being studied. In summary, the drug treatment of hypercholesterolemia in pediatric patients is expanding beyond the use of statins, and now involves multiple mechanisms of action involving cholesterol metabolism. As younger pediatric patients are diagnosed and treated for HeFH and HoFH, optimizing the doses of these agents and safety studies specific in younger pediatric patients will be necessary. This article is protected by copyright. All rights reserved.