Advanced data modeling performed by researchers in the University of Florida College of Pharmacy has paved the way for a newly approved pediatric treatment for a rare and fatal genetic cholesterol disorder.
In March, the U.S. Food and Drug Administration approved the drug lomitapide for children over the age of 2 with homozygous familial hypercholesterolemia, or HoFH. The disease causes severely elevated cholesterol levels from birth and leads to heart attacks and cardiovascular disease during childhood or adolescence if left untreated. HoFH affects an estimated 1 in 170,000 to 1 in 300,000 individuals worldwide.
The approval was supported in part by pharmacokinetic and pharmacodynamic analyses conducted by faculty in the UF College of Pharmacy’s Department of Pharmaceutics and the Center for Pharmacometrics and Systems Pharmacology. The UF researchers developed model-informed dosing recommendations that demonstrated the medication could safely and effectively reduce harmful low-density lipoprotein, or LDL, cholesterol levels in pediatric patients.
“UF has built a strong reputation for providing the advanced modeling and data analysis that the pharmaceutical industry relies upon during the drug development and regulatory approval process,” said Brian Cicali, Ph.D., M.S., an assistant professor of pharmaceutics in the UF College of Pharmacy. “In this case, our analysis demonstrated that lomitapide could be used safely and effectively in pediatric patients, giving children with HoFH access to a treatment that can significantly improve and extend their lives.”
Although lomitapide has been FDA-approved for adults with HoFH since 2012, families with young children affected by the disease have spent years waiting for an approved pediatric therapy.
“This is a life-changing decision for the HoFH community,” Cicali said. “The ability to take a pill once a day to prevent these serious disease outcomes opens up opportunities for families that did not exist before.”
Using advanced model-informed drug development techniques, the UF team evaluated dosing strategies, age-specific maximum doses and the medication’s overall safety and efficacy profile in children. The findings showed that lomitapide produced substantial reductions in LDL cholesterol levels among pediatric patients while maintaining liver health.
The researchers recommended a starting dose of 2 milligrams for children ages 2 to 15 years and 5 milligrams for patients older than 15 years. Maximum recommended doses ranged from 20 milligrams for younger pediatric patients to 40 milligrams for older adolescents.
“A critical driver for developing these model-informed dosing recommendations was the absence of an approved pediatric lomitapide regimen despite its long-established use in adults with HoFH,” Cicali said. “This medication is going to make a significant difference in the lives of children who are affected by HoFH and will allow them to live beyond the very limited life expectancy for someone who is not treated.”
In addition to the FDA’s approval, the European Medicines Agency recently issued a favorable opinion supporting lomitapide for children older than 5 years, and the European Commission has since officially approved the medication for pediatric use in the European Union. The medication is also approved for use in children in Saudi Arabia.
Reaching these regulatory milestones reflects more than a decade of work by current and former faculty in the UF College of Pharmacy, who have provided critical expertise in study design, data analysis and regulatory strategy to support pediatric approval efforts.
Chiesi Global Rare Diseases, a business unit of Chiesi Group, is responsible for developing, commercializing and expanding access to lomitapide for patients with HoFH. The medication is sold under the brand name Juxtapid® in the U.S.