The Food and Drug Administration (FDA) has approved Repatha (evolocumab) injection as an adjunct to diet and other low-density lipoprotein cholesterol (LDL-C)-lowering therapies in patients 10 years of age and older with heterozygous familial hypercholesterolemia (HeFH). Previously, the treatment was indicated only in adults 18 years of age and older.
The approval was based on the multicenter, randomized, double-blind, placebo-controlled phase 3b HAUSER-RCT trial (ClinicalTrials.gov Identifier: NCT02392559), which evaluated the efficacy and safety of evolocumab in 157 patients 10 to 17 years of age with HeFH. Patients were required to be on a low-fat diet and optimized LDL-C lowering therapy. Patients were randomly assigned 2:1 to receive evolocumab 420mg subcutaneously once monthly (n=104) or placebo (n=53) for 24 weeks.
Findings showed that treatment with evolocumab met the primary endpoint demonstrating a mean reduction in LDL-C of 38% (95% CI, 45-31; P <.0001) at week 24 from baseline compared with placebo. Additionally, evolocumab led to improvements in key secondary endpoints at week 24 compared with placebo, including a 35% (95% CI, 42-28) reduction in non-high-density lipoprotein cholesterol, a 32% (95% CI, 39-26) reduction in apolipoprotein B, and a 27% (95% CI, 32-21) reduction in total cholesterol.
As for safety, the most common treatment-emergent adverse events were nasopharyngitis, headache, oropharyngeal pain, influenza and upper respiratory tract infection.
The FDA also expanded the approval of Repatha as an adjunct to other LDL-C lowering therapies for the treatment of patients 10 years of age and older with homozygous familial hypercholesterolemia (HoFH). Previously, the treatment was indicated only in patients 13 years of age and older.
The approval was based on data from the open-label, single-arm phase 3 HAUSER-OLE trial (ClinicalTrials.gov Identifier: NCT02624869) that evaluated the efficacy and safety of evolocumab 420mg subcutaneously once monthly in patients 10 to 17 years of age with HoFH. Results showed that treatment with evolocumab led to a median 14% reduction in LDL-C from baseline to week 80.
“The approval of Repatha for pediatric patients with FH represents a much-needed adjunct treatment option for these children with genetically high cholesterol who are unable to manage their high LDL-C with other lipid-lowering agents alone,” said David M. Reese, MD, executive vice president of Research and Development at Amgen. “This milestone further reinforces the safety profile of Repatha and aligns with Amgen’s commitment to addressing the unmet needs of the high-risk cardiovascular community.”
Repatha is also approved to reduce the risk of myocardial infarction, stroke, and coronary revascularization in adults with established cardiovascular disease.
- FDA approves add-on drug for ages 10 & up with rare forms of high cholesterol. News release. US Food and Drug Administration. September 24, 2021. Accessed September 27, 2021. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-add-drug-ages-10-rare-forms-high-cholesterol.
- FDA approves Repatha® (evolocumab) in pediatric patients age 10 and older with heterozygous familial hypercholesterolemia. News release. Amgen. September 24, 2021. Accessed September 27, 2021. https://www.amgen.com/newsroom/press-releases/2021/09/fda-approves-repatha-evolocumab-in-pediatric-patients-age-10-and-older-with-heterozygous-familial-hypercholesterolemia.
- Repatha. Package insert. Amgen; 2021. Accessed September 24, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125522s29s31lbl.pdf.