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Review
. 2022 Dec 25;12(1):168.
doi: 10.3390/jcm12010168.

Evinacumab, an ANGPTL3 Inhibitor, in the Treatment of Dyslipidemia

Bożena Sosnowska  1 , Weronika Adach  1 , Stanisław Surma  2 , Robert S Rosenson  3 , Maciej Banach  1   4   5
Affiliations
Review

Evinacumab, an ANGPTL3 Inhibitor, in the Treatment of Dyslipidemia

Bożena Sosnowska et al. J Clin Med. .

Abstract

Familial hypercholesterolemia (FH) is an inherited disorder. The level of low-density lipoprotein cholesterol (LDL-C) in patients with homozygous FH can be twice as high as that in patients with heterozygous FH. The inhibition of ANGPTL3 shows an important therapeutic approach in reducing LDL-C and triglycerides (TG) levels and, thus, is a potentially effective strategy in the treatment of FH. Evinacumab is a monoclonal antibody inhibiting circulating ANGPTL3, available under the trade name Evkeeza® for the treatment of homozygous FH. It was reported that evinacumab is effective and safe in patients with homozygous and heterozygous FH, as well as resistant hypercholesterolemia and hypertriglyceridemia. This paper summarizes existing knowledge on the role of ANGPTL3, 4, and 8 proteins in lipoprotein metabolism, the findings from clinical trials with evinacumab, a fully human ANGPTL3 mAb, and the place for this new agent in lipid-lowering therapy.

Keywords: ANGPTL3 inhibitors; LDL cholesterol; evinacumab; familial hypercholesterolemia.

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Conflict of interest statement

B.S., W.A., S.S.—no conflict of interest; R.S.R.—receives research grants to his institution from Amgen, Arrowhead, Eli Lilly, Novartis, and Regeneron; consulting fees from Amgen, Arrowhead, CRISPR Therapeutics, Eli Lilly, Precision BioSciences, Regeneron, and Ultragenyx; and royalties from Wolters Kluwer (UpToDate) and has stock holdings in MediMergent, LLC; M.B.—speakers bureau: Amgen, Herbapol, Kogen, KRKA, Polpharma, Mylan/Viatris, Novartis, Novo-Nordisk, Sanofi-Aventis, Teva, and Zentiva; consultant to Abbott Vascular, Amgen, Daichii Sankyo, Esperion, Freia Pharmaceuticals, NewAmsterdam, Novartis, Polfarmex, and Sanofi-Aventis; grants from Amgen, Mylan/Viatris, Sanofi, and Valeant; and CMO at the Nomi Biotech Corporation.

Figures

Figure 1
Figure 1
Regulation of triglyceride metabolism in heart, muscle, brown adipose tissue, and white adipose tissue by ANGPTL3, ANGPTL4, and ANGPTL8. Abbreviations: TG—triglyceride; TLR—triglyceride-rich lipoprotein; LPL—lipoprotein lipase; ANGPTL3—angiopoietin-like protein 3; ANGPTL4—angiopoietin-like protein 4; ANGPTL8—angiopoietin-like protein 8. The following was used in the preparation of the figure: https://smart.servier.com (free-access; 20 October 2022).
Figure 2
Figure 2
Evinacumab—mechanism of action. Abbreviations: ANGPTL3—angiopoietin-like protein 3; EL—endothelial lipase; IDL—intermediate-density lipoprotein (VLDL remnants); IDL-R—intermediate-density lipoprotein receptor (VLDL remnant receptor); LDL—low-density lipoprotein; LDL-C—low-density lipoprotein; LDL-R—low-density lipoprotein receptor; LPL—lipoprotein lipase; VLDL—very-low-density lipoprotein. The following was used in the preparation of the figure: https://smart.servier.com (free-access; 20 October 2022).
See this image and copyright information in PMC

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