evinacumab   

GtoPdb Ligand ID: 8717

Synonyms: REGN1500
Compound class: Antibody
Comment: Evinacumab is a fully human investigational monoclonal antibody targeting angiopoietin-like 3 (ANGPTL3). Due to its role in lipid metabolism, ANGPTL3 is being investigated as a potential molecular target for the treatment of hypertriglyceridemia in cardiovascular disease.
Peptide sequence and structural information for this antibody are available from its IMGT/mAb-db record.
A BLAST search of patented peptide sequences reveals that the heavy chain variable domain of evinacumab is identical to SEQ ID: NO 66 from patent US9018356 B2 [3], and the light chain variable region is identical to SEQ ID: NO 74 from the same patent (this heavy/light chain combination corresponds to antibody identifier H4H1276S).
No information available.
Summary of Clinical Use
Evinacumab has reached Phase II clinical trial for its potential to treat homozygous familial hypercholesterolemia (HoFH). Click here to view ClinicalTrials.gov's full list of evinacumab trials.
Mechanism Of Action and Pharmacodynamic Effects
ANGPTL3 inhibits lipoprotein lipase (LPL) activity leading to increased level of lipids [1], and subsequently regulates very low density lipoprotein (VLDL) triglyceride levels [2]. The N-terminal coiled-coil region of ANGPTL3 inhibits LPL when expressed without the C-terminal fibrinogen region and therefore appears to confer its inhibitory function. The H4H1276S antibody clone in patent US9018356 B2, presumed to be evinacumab, inhibits the ANGPTL3-induced decrease in LPL activity in vitro [3], but does not block ANGPTL4-induced decrease in LPL activity. H4H1276S shows cross-species activity, inhibiting mouse and monkey ANGPTL3 at comparable levels to the human protein [3].