Evinacumab — an ANGPTL3 inhibitor; a new drug in the treatment of lipid disorders. Review on the literature and clinical studies
open access
Abstract
Angiopoietin-like proteins (ANGPTL) are a family of several proteins, of which ANGPTL3, 4 and 8 are involved in lipid metabolism. These proteins, discovered relatively recently, regulate the availability of triglycerides for the heart, skeletal muscles and white and brown adipose tissue depending on the nutritional status of the body, thus contributing to the maintenance of energy homeostasis. ANGPTL3, 4 and 8 gene mutations are associated with a significant reduction in plasma lipid levels, which translates to a reduction in the risk of ischaemic heart disease and diabetes type 2. It was shown that blood levels of ANGPTL3, 4, 5 and 8 may change in various disease states, such as obesity or diabetes type 2, and thus may constitute biomarkers of the cardiovascular risk. Evinacumab, being a fully humanized anti-ANGPTL3 antibody, February, 11th, 2021, as Evkeeza® preparation, has been registered by the US Food and Drug Administration for the treatment of homozygous familial hypercholesterolaemia. In clinical trials, evinacumab was characterized by a high lipid-lowering efficacy in patients with homozygous and heterozygous familial hypercholesterolaemia, as well as treatment-resistant hypercholesterolaemia and hypertriglyceridaemia. Another drug that reduces ANGPTL3 activity are antisense oligonucleotides targeting Angptl3 mRNA (ANGPTL3 ASO) which were also characterized by lipid lowering properties in clinical trials.
Abstract
Angiopoietin-like proteins (ANGPTL) are a family of several proteins, of which ANGPTL3, 4 and 8 are involved in lipid metabolism. These proteins, discovered relatively recently, regulate the availability of triglycerides for the heart, skeletal muscles and white and brown adipose tissue depending on the nutritional status of the body, thus contributing to the maintenance of energy homeostasis. ANGPTL3, 4 and 8 gene mutations are associated with a significant reduction in plasma lipid levels, which translates to a reduction in the risk of ischaemic heart disease and diabetes type 2. It was shown that blood levels of ANGPTL3, 4, 5 and 8 may change in various disease states, such as obesity or diabetes type 2, and thus may constitute biomarkers of the cardiovascular risk. Evinacumab, being a fully humanized anti-ANGPTL3 antibody, February, 11th, 2021, as Evkeeza® preparation, has been registered by the US Food and Drug Administration for the treatment of homozygous familial hypercholesterolaemia. In clinical trials, evinacumab was characterized by a high lipid-lowering efficacy in patients with homozygous and heterozygous familial hypercholesterolaemia, as well as treatment-resistant hypercholesterolaemia and hypertriglyceridaemia. Another drug that reduces ANGPTL3 activity are antisense oligonucleotides targeting Angptl3 mRNA (ANGPTL3 ASO) which were also characterized by lipid lowering properties in clinical trials.
Keywords
ANGPTL3, ANGPTL4, ANGPTL8, evinacumab, ANGPTL3 ASO, treatment of lipid disorders
About this articleTitle
Evinacumab — an ANGPTL3 inhibitor; a new drug in the treatment of lipid disorders. Review on the literature and clinical studies
Journal
Issue
Article type
Review paper
Pages
30-39
DOI
10.5603/FC.2021.0005
Bibliographic record
Folia Cardiologica 2021;16(1):30-39.
Keywords
ANGPTL3
ANGPTL4
ANGPTL8
evinacumab
ANGPTL3 ASO
treatment of lipid disorders
Authors
Stanisław Surma
Monika Romańczyk
Krzysztof J. Filipiak