evinacumab   Click here for help

GtoPdb Ligand ID: 8717

Synonyms: evinacumab-dgnb | Evkeeza® | REGN1500
Approved drug
evinacumab is an approved drug (EMA & FDA (2021))
Compound class: Antibody
Comment: Evinacumab is a fully human 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.
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).

Evinacumab utilises a different molecular mechanism compared to Regeneron's already approved anti-hyperlipidemic drug alirocumab (targets proprotein convertase subtilisin/kexin type 9).
No information available.
Summary of Clinical Use Click here for help
Evinacumab was advanced to clinical trial for its potential to treat homozygous familial hypercholesterolemia (HoFH), which is an ultra-rare genetic disease. HoFH is a difficult to treat disease, with patients struggling to control their cholesterol levels. The FDA granted evicanumab priority review in August 2020, as an adjunct to other lipid-lowering therapies in patients with HoFH. FDA's decision to approve evinacumab for this indication was announced in February 2021. EMA approval followed in July of the same year.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
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].