Evinacumab - a new drug in the treatment of homozygous familial hypercholesterolaemia

Abstract

Evinacumab, being a fully humanized anti-ANGPTL3 monoclonal antibody, February, 11th, 2021, as Evkeeza® preparation, has been registered by the U.S. Food & Drug Administration for the treatment of homozygous familial hypercholesterolaemia (HoHF).Angiopoietin-like proteins (ANGPTL) include the compounds ANGPTL1 through ANGPTL8 and belong to the vascular endothelial growth factor (VEGF) family. ANGPTL3, ANGPTL4 and ANGPTL8 play an important role in terms of cardiovascular physiology and lipid metabolism. These proteins regulate the metabolism of triglyceride-rich lipoproteins [1,2]. The main source of ANGPTL3 is liver, ANGPTL4 is liver, adipose tissue, skeletal muscle, gut, heart and brain, and ANGPTL8 is liver and adipose tissue. These proteins form a ANGPTL3-4-8 system that controls the availability of triglycerides depending on the current nutritional status of the body, temperature and physical activity (Figure 1) [1,2].

Evinacumab – The new kid on the block. Is it important for cardiovascular prevention?

“…Angiopoietin-like proteins (ANGPTL) include the compounds ANGPTL1 through ANGPTL8 and belong to the vascular endothelial growth factor (VEGF) family [ [1] , [2] , [3] ].…”

“…The main source of ANGPTL3 is liver, ANGPTL4 is from liver, adipose tissue, skeletal muscle, gut, heart and brain, and ANGPTL8 is from liver and adipose tissue. These proteins form a ANGPTL3-4-8 system that controls the availability of triglycerides depending on nutritional status, temperature, and physical activity [ [1] , [2] , [3] , 5 ].…”

“…In the heart, skeletal muscle, and brown adipose tissue, the activity of LPL after a meal is reduced by ANGPTL3 and ANGPTL8 (after a meal, the expression of ANGPTL8 is particularly increased, while the expression of ANGPTL3 is not dependent on the nutritional status) forming a heterodimer (ANGPTL8 is an activator of ANGPTL3). Thus, the ANGPTL3-4-8 system plays an important role in regulating triglyceride metabolism [ [1] , [2] , [3] , 5 ].…”

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Fig. 1 ANGPTL3-4-8 system mechanism of action in the regulation of triglyceride-rich lipoprotein metabolism [ [1] , [2] , [3] , 5 ]. ANGPTL3 – angiopoetin-like protein 3; ANGPTL4 - angiopoetin-like protein 4; ANGPTL8 - angiopoetin-like protein 8; TLR - triglyceride-rich lipoprotein.

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Editorial comments to the articles published in Volume 8

“…Other review articles (i.e. Mini-Reviews) summarized: 1) the role of probiotics and prebiotics in preventing colorectal carcinogenesis [4]; 2) the potential application of phytotherapy against cancer [5]; 3) the efficacy of evinacumab, an anti-ANGPTL3 monoclonal antibody, against homozygous familial hypercholesterolemia [6]; and 4) the potential role of exosomes, particularly as a therapeutic target, in human malignancies [7].…”