Alirocumab Approved for Heterozygous Familial Hypercholesterolemia in Patients 8 Years and Older

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Nearly a decade after becoming the first PCSK9 inhibitor to receive approval from the FDA, alirocumab (Praluent) has now received approval for pediatric patients with HeFH based on data from a phase 3 trial.

The US Food and Drug Administration has approved alirocumab (Praluent) to treat heterozygous familial hypercholesterolemia (HeFH) in pediatric patients aged 8 years and older.

Announced on March 11, 2024 by Regeneron Pharmaceuticals, the approval, which indicates the agent as an adjunct to diet and other LDL-C lowering therapies, is based on the results of a 24-week, phase 3 trial of 153 pediatric patients with HeFH inadequately controlled by statin therapy.1

“Many children with heterozygous familial hypercholesterolemia (HeFH) are able to substantially improve their LDL-C (bad cholesterol) with currently available therapies. But for those children whose LDL-C remains dangerously high, this approval is an important milestone as it gives these children and their families an additional option to help reduce and manage their LDL-C levels much earlier in their lives,” said Mary P. McGowan, MD, chief medical officer of the Family Heart Foundation.1

Hailed as the first PCSK9 inhibitor approved by the FDA, alirocumab boasts FDA approvals for reducing secondary events in cardiovascular disease, to lower LDL-C in primary hyperlipidemia, and homozygous familial hypercholesterolemia dating back to 2015 prior to receiving its latest indication in HeFH. An inherited genetic disorder characterized by elevated cholesterol levels, HeFH impacts an estimated 25 million people in the US, with data indicating parents with HeFH have a 50% chance of passing the altered gene responsible for the autosomal genetic disorder to their offspring.2,3

According to Regeneron, the latest approval as an adjunct for HeFH is based on data from a phase 3 randomized, placebo-controlled trial of 153 patients aged 8 to 17 years. Published in JAMA Pediatrics, the trial randomized patients in a 2:1 ratio to alirocumab or placebo therapy for a 24-week treatment period. For the purpose of analysis, patients received alirocumab every 2 or every 4 weeks. The primary outcome of interest for the trial was the percent change in LDL-C from baseline to week 24 in each cohort. 1,4

Of note, dosing strength in the trials was based on weight and adjusted at week 12 if LDL-C was 110 mg/dL or greater at week 8. In the JAMA Pediatrics publication, investigators pointed out patients could receive alirocumab during an 80-week open-label period after the 24-week double-blind period.4

Upon analysis, results indicated alirocumab use was associated with significantly reduced LDL-C compared with placebo in both dosing cohorts at week 24, with a least squares (LS) mean difference of −43.3% (97.5% CI, −56.0 to −30.7; P < .001) in the every 2 weeks group and −33.8% (97.5% CI, −46.4 to −21.2; P < .001) in the every 4 weeks group. The trial also included key secondary endpoints and results of the investigators' analyses indicated alirocumab was associated with significant reductions relative to placebo therapy through hierarchical testing of the first 12 key secondary efficacy outcomes, including apo B, non-HDL-C, and total cholesterol.4

Analysis of safety outcomes revealed 2 patients in the alirocumab every 4 weeks group discontinued treatment due to adverse events, but there was no significant difference in adverse event incidence among the study groups, according to investigators. Analysis of available open-label data suggested the LDL-C reductions achieved in the double-blind period were well maintained in patients who received alirocumab and those who switched from placebo to alirocumab had reductions in LDL-C at week 32 and were maintained through week 104.4

“The approval of Praluent for the treatment of high cholesterol was a historic landmark achievement, as it was the first approved therapy targeting the genetically-validated PCSK9 target for heart disease,” said George D. Yancopoulos, MD, PhD, board co-chair, president and, chief scientific officer at Regeneron, and a principal inventor of Praluent.1 “Praluent has made a meaningful impact in the treatment of adults with familial hypercholesterolemia, and we are proud that our innovation will now be able to help appropriate children with the heterozygous form of this disease manage their dangerously high levels of LDL-C.”


  1. Regeneron Pharmaceuticals Inc. Praluent® (alirocumab) injection receives FDA approval to treat children with genetic form of high cholesterol. Regeneron Pharmaceuticals Inc. March 11, 2024. Accessed March 11, 2024.
  2. Regeneron Pharmaceuticals Inc. Regeneron and Sanofi announce FDA approval of Praluent® (alirocumab) injection, the first PCSK9 inhibitor in the U.S., for the treatment of high LDL cholesterol in adult patients. Regeneron Pharmaceuticals Inc. July 24, 2015. Accessed March 11, 2024.
  3. Centers for Disease Control and Prevention. Familial hypercholesterolemia. Centers for Disease Control and Prevention. June 16, 2023. Accessed March 11, 2024.
  4. Santos RD, Wiegman A, Caprio S, et al. Alirocumab in Pediatric Patients With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial. JAMA Pediatr. 2024;178(3):283–293. doi:10.1001/jamapediatrics.2023.6477