Evinacumab Gets Priority Review for Homozygous Familial Hypercholesterolemia

Pexidartinib is an oral small molecule that is believed to work by inhibiting colony stimulating factor-1 receptor (CSF1R).
Evinacumab is an investigational fully-human monoclonal antibody that binds to and blocks the function of angiopoietin-like 3 (ANGPTL3).

The Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) for evinacumab (Regeneron) as an adjunct to other lipid-lowering therapies in patients with homozygous familial hypercholesterolemia (HoFH).

Evinacumab is an investigational fully-human monoclonal antibody that binds to and blocks the function of angiopoietin-like 3 (ANGPTL3) using the Company’s proprietary VelocImmune® technology. ANGPTL3 acts as an inhibitor of lipoprotein lipase and endothelial lipase, and appears to play a central role in lipoprotein metabolism.

The BLA submission is supported by data from the double-blind, placebo-controlled phase 3 ELIPSE HoFH trial that evaluated the efficacy and safety of evinacumab in 65 patients aged ≥12 years with HoFH. Patients were randomized 2:1 to receive either evinacumab 15mg/kg intravenously every 4 weeks or placebo. In the evinacumab treatment arm, patients were on the following lipid-lowering therapies: statins (98%), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (81%), ezetimibe (75%), LDL apheresis (33%), lomitapide (26%). The primary end point was the reduction of low-density lipoprotein cholesterol (LDL-C) from baseline to week 24.

Results showed that at week 24, patients treated with evinacumab had a 47% reduction in LDL-C compared with a 2% increase for patients treated with placebo (absolute change in LDL-C from baseline was 132mg/dL; P <.0001). Moreover, 47% of patients in the evinacumab arm achieved LDL-C levels of <100mg/dL (average baseline LDL-C level was 260mg/dL) compared with 23% in the placebo arm (nominal P =.0203).

In addition, the study met key secondary end points with 84% and 56% of patients in the evinacumab arm achieving at least 30% and 50% reductions, respectively, in LDL-C levels compared with 19% and 5% for placebo, respectively (P <.0001 and P =.0003). Evinacumab was also associated with statistically significant reductions in levels of apolipoprotein B, non-high-density lipoprotein cholesterol, total cholesterol and triglycerides, compared with placebo (P <.0001 for all).

As for safety, evinacumab was generally well tolerated with the most common adverse events being influenza-like illness (11% evinacumab vs 0% placebo) and rhinorrhea (7% evinacumab vs 0% placebo).

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A Prescription Drug User Fee Act (PDUFA) target date of February 11, 2021 has been assigned to this application.

For more information visit regeneron.com.


  1. FDA accepts evinacumab Biologics License Application for Priority Review as a treatment for patients with HoFH, an ultra-rare inherited form of high cholesterol. https://www.prnewswire.com/news-releases/fda-accepts-evinacumab-biologics-license-application-for-priority-review-as-a-treatment-for-patients-with-hofh-an-ultra-rare-inherited-form-of-high-cholesterol-301110441.html. Accessed August 12, 2020. 
  2. Regeneron announces American College of Cardiology presentation of positive phase 3 evinacumab results in patients with severe inherited form of high cholesterol. https://investor.regeneron.com/index.php/news-releases/news-release-details/regeneron-announces-american-college-cardiology-presentation. Accessed August 12, 2020.