Evinacumab Reduces LDL-C in Pediatric Patients with Hypercholesterolemia

In patients aged 12 years or younger with homozygous familial hypercholesterolemia, evinacumab therapy can significantly decrease LDL-C concentrations.

Low-density lipoprotein cholesterol (LDL-C) concentrations are dramatically reduced by evinacumab therapy in pediatric patients with homozygous familial hypercholesterolemia (HOFH) uncontrolled with standard lipid-lowering therapies. These findings were presented at the National Lipid Association (NLA) Scientific Sessions 2023, held in Atlanta, Georgia, between June 1 and June 4, 2023.

Researchers aimed to assess the safety and efficacy of evinacumab in young pediatric patients with HOFH. During Part B of the study, among the intent-to-treat (ITT) population, mean percent change in LDL-C to week 24 from baseline was the primary efficacy endpoint.

The researchers conducted an open-label, multicenter, 3-part study (ClinicalTrials.gov Identifier: NCT04233918) that included 6 patients in Part A (mean age, 8.8±1.7 years; 67% girls), 14 patients in Part B (mean age, 9.1±1.9 years; 57% girls), and all 20 of these patients in an ongoing Part C. Inclusion criteria included the patients being aged 5 to 11 years, with LDL-C greater than 130 mg/dL while being treated with lipid-lowering therapy.

Part A (16-week Phase 1b, open-label, single dose intravenous (IV) evinacumab 15 mg/kg) aimed to evaluate pharmacokinetics, pharmacodynamics, and safety of evinacumab. Part B (24-week Phase 3, open-label, evinacumab 15 mg/kg IV every 4 weeks [Q4W]) aimed to evaluate the efficacy and safety of evinacumab in 14 patients who did not participate in Part A. Part C (48-week Phase 3 on-going, open-label extension with 24-week follow-up, evinacumab 15 mg/kg IV Q4W) aimed to evaluate long-term efficacy and safety of evinacumab and included all 20 patients from Parts A and B.

There was a mean maximum LDL-C reduction of 41.6% (SD, 18.3%) after 8 weeks among all 6 patients in Part A. Of patients in Part B, 78.6% experienced at least a 50% reduction in LDL-C after 24 weeks. At week 24, among the 14 patients in Part B, there was a mean percent change from baseline of -48.3%±10.4%. Additional mean percent changes from baseline to week 24 occured (total cholesterol, -49.1%±8.1%; non-high-density lipoprotein cholesterol, -48.9%±9.8%; apolipoprotein B, -41.3%±9.0%).

There was a -43.0%±12.8% mean percent change in LDL-C for patients with a defective/negative low-density lipoprotein receptor (LDLR) variant (LDLR activity >15%) and -67.7%±6.5% for patients with a negative/negative LDLR variant (LDLR activity ≤15%).

The researchers noted that 10 of the 14 patients in Part B experienced treatment-emergent adverse events (TEAEs). There were 2 of these patients in whom TEAEs were treatment-related (abdominal pain and nausea). Additionally, patients experienced oropharyngeal pain (n=3), diarrhea (n=2), vomiting (n=2), headache (n=2), and nasopharyngitis (n=2). There was 1 patient who experienced a serious TEAE (tonsilitis), not considered treatment-related. There were 3 patients who experienced at least 1 severe TEAE. They reported no deaths or treatment discontinuations due to TEAEs.

A limitation of this study is the small sample size.

“In very-young pediatric patients with HOFH (aged 5–11 years) and inadequately controlled LDL-C despite optimized lipid-lowering therapy (including apheresis and lomitapide), evinacumab rapidly and durably lowered LDL-C, with considerable reductions of 48% by week 24,” the researchers wrote. “Evinacumab was generally well tolerated, and the safety profile remained consistent with that observed in adult and adolescent patients, with no new safety signals observed.”

Disclosure: This research was supported by Regeneron Pharmaceuticals, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Wiegman A, Greber-Platzer S, Ali S, et al. Efficacy and safety of evinacumab in pediatric patients with homozygous familial hypercholesterolemia. Abstract presented at: National Lipid Association (NLA) Scientific Sessions 2023; June 1-4, 2023; Atlanta, GA. Abstract #111