Evinacumab Under Review for Pediatric Homozygous Familial Hypercholesterolemia

The Food and Drug Administration (FDA) has accepted for Priority Review the supplemental Biologics License Application (sBLA) for evinacumab-dgnb as an adjunct to other lipid-lowering therapies to treat children aged 5 to 11 years with homozygous familial hypercholesterolemia (HoFH). An FDA target action date of March 30, 2023 has been set for the application.

Evinacumab is a fully-human monoclonal antibody that binds to and blocks the function of angiopoietin-like 3 (ANGPTL3). The sBLA is supported by data from a 3-part single-arm, open-label trial (ClinicalTrials.gov Identifier: NCT04233918) that evaluated the efficacy and safety of evinacumab in 14 pediatrics patients (average age, 9 years) with HoFH who were enrolled in the Part B portion of the trial. Patients had an average LDL-C level of 264mg/dL and were on the following lipid-lowering therapies: statins (86%), ezetimibe (93%), LDL apheresis (50%), and lomitapide (14%). 

Patients received evinacumab 15mg/kg intravenously every 4 weeks in addition to lipid-lowering therapies for 24 weeks. The primary endpoint was the change in LDL-C from baseline to week 24. Key secondary endpoints included the effect of evinacumab on other lipid parameters.

Results showed evinacumab met the primary endpoint demonstrating a mean reduction in LDL-C of 48% at week 24. Treatment with evinacumab reduced LDL-C by at least half in 79% of patients and was associated with an absolute mean reduction in LDL-C of 132mg/dL.

Reductions were also observed in levels of all lipid endpoint parameters (apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein(a), and total cholesterol), generally within the first 8 weeks of treatment.

A long-term safety analysis (mean exposure: 52 weeks) showed the most common adverse reactions were COVID-19, pyrexia, headache, oropharyngeal pain, upper abdominal pain, diarrhea, vomiting, fatigue, nasopharyngitis, rhinitis and cough. None of these adverse events led to drug discontinuation.

Evinacumab is currently marketed under the brand name Evkeeza® as an adjunct to other LDL-C lowering therapies for the treatment of patients 12 years of age and older with HoFH.

This article originally appeared on MPR


Evkeeza® (evinacumab-dgnb) sBLA for children with ultra-rare inherited form of high cholesterol accepted for FDA Priority Review. News release. Regeneron Pharmaceuticals, Inc. Accessed November 30, 2022. https://www.prnewswire.com/news-releases/evkeeza-evinacumab-dgnb-sbla-for-children-with-ultra-rare-inherited-form-of-high-cholesterol-accepted-for-fda-priority-review-301690183.html