Evinacumab

Evinacumab Uses, Dosage, Side Effects, Food Interaction and all others data.

Evinacumab is a recombinant human IgG4 monoclonal antibody targeted against angiopoietin-like protein 3 (ANGPTL3) and the first drug of its kind. The ANGPTL family of proteins serve a number of physiologic functions - including involvement in the regulation of lipid metabolism - which have made them desirable therapeutic targets in recent years. Loss-of-function mutations in ANGPTL3 have been noted to result in hypolipidemia and subsequent reductions in cardiovascular risk, whereas increases in function appear to be associated with cardiovascular risk, and it was these observations that provided a rationale for the development of a therapy targeted against ANGPTL3.

In February 2021, evinacumab became the first-and-only inhibitor of ANGPTL3 to receive FDA approval after it was granted approval for the adjunctive treatment of homozygous familial hypercholesterolemia (HoFH) under the brand name "Evkeeza". Evinacumab is novel in its mechanism of action compared with other lipid-lowering therapies and therefore provides a unique and synergistic therapeutic option in the treatment of HoFH.

Evinacumab exerts its hypolipidemic and antiatherogenic effects via decreasing circulating levels of triglycerides, HDL-C, and LDL-C, apolipoprotein B, and total cholesterol. It is has a relatively long duration of action that allows for its administration via intravenous injection once-monthly.

Evinacumab
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Evinacumab
Availability	Prescription only
Generic	Evinacumab
Evinacumab Other Names	Evinacumab, evinacumab-dgnb
Related Drugs	atorvastatin, simvastatin, rosuvastatin, Lipitor, Crestor, Zocor
Weight	150mg/ml
Type	Intravenous solution
Weight	146000.0 Da
Groups	Approved, Investigational
Therapeutic Class
Manufacturer
Available Country	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Evinacumab is a monoclonal antibody targeted against angiopoetin-like protein 3 (ANGPTL3) used as an adjunct with other lipid-lowering therapies for the treatment of homozygous familiar hypercholesterolemia.

Evinacumab is indicated, as an adjunct with other lipid-lowering therapies, for the treatment of familial homozygous hypercholesterolemia (HoFH) in patients 12 years of age and older.

Evinacumab is also used to associated treatment for these conditions: Homozygous Familial Hypercholesterolemia

How Evinacumab works

Angiopoetin-like proteins (ANGPTL) are a diverse group of proteins involved in a number of physiological processes, including the regulation of lipoprotein metabolism. Loss-of-function mutations in ANGPTL3 and ANGPTL4 have been shown to result in hypolipidemia and a reduced risk of coronary artery disease, while increased levels of these proteins appear to be associated with cardiovascular risk. While these observations have made ANGPTLs as a class a desirable target in the treatment of hyperlipidemic disorders, ANGPTL3 is the first to be pharmacologically targeted for the purposes of lipid-lowering therapy. ANGPTL3 is expressed primarily in the liver and acts as an endogenous inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL) which are responsible, in part, for metabolizing triglycerides (TG) and HDL-C, respectively.

Evinacumab is monoclonal antibody that binds to and inhibits ANGPTL3, with the resulting disinhibition of LPL and EL reducing the levels of circulating TG and HDL-C. While the mechanism through which evinacumab reduces LDL-C is not entirely clear, this effect is independent of LDL receptor density and is therefore most likely due to the promotion of VLDL processing and upstream clearance of LDL formation.

Toxicity

There are no data regarding overdosage with evinacumab. Symptoms of overdose are likely to be consistent with evinacumab's adverse effect profile and may therefore include significant infusion reactions or dizziness. Patients experiencing an overdose should be treated with symptomatic and supportive measures.

Food Interaction

No interactions found.

Volume of Distribution

The volume of distribution of evinacumab was estimated to be 4.8 L via population pharmacokinetic analysis.

Elimination Route

Following the recommended dosing regimen (15 mg/kg intravenously every 4 weeks), steady-state concentrations are reached after four doses. According to population pharmacokinetic modeling, the mean steady-state trough concentration is approximately 241 mg/L and the C_max at the end of infusion is approximately 689 mg/L.

Half Life

The elimination half-life of evinacumab is a function of its serum concentration and is therefore variable. This is because evinacumab is eliminated by two parallel pathways: at higher concentrations it is eliminated primarily through a non-saturable proteolytic pathway, while at lower concentrations its elimination occurs primarily via a saturable target-mediated pathway.

Elimination Route

Monoclonal antibodies are typically eliminated via uptake into cells and subsequent catabolism via lysosomal degradation. Due to their large size, they are only eliminated renally under pathologic conditions.