Evinacumab API Manufacturers

General Description:

Evinacumab, identified by CAS number 1446419-85-7, is a notable compound with significant therapeutic applications. 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.

Indications:

This drug is primarily indicated for: 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. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Evinacumab undergoes metabolic processing primarily in: The biotransformation of evinacumab has not been characterized. Monoclonal antibodies as a class are typically degraded via catabolic pathways into smaller peptides and amino acids. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Evinacumab are crucial for its therapeutic efficacy: 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. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Evinacumab is an important consideration for its dosing schedule: 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. This determines the duration of action and helps in formulating effective dosing regimens.

Route of Elimination:

The elimination of Evinacumab from the body primarily occurs through: 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. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Evinacumab is distributed throughout the body with a volume of distribution of: The volume of distribution of evinacumab was estimated to be 4.8 L via population pharmacokinetic analysis. This metric indicates how extensively the drug permeates into body tissues.

Pharmacodynamics:

Evinacumab exerts its therapeutic effects through: 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. Animal studies have demonstrated embryo-fetal toxicity - administration to pregnant rabbits during organogenesis resulted in increases in fetal malformations at concentrations lower than those used in humans. For this reason, patients receiving therapy with evinacumab should obtain a pregnancy test prior to beginning therapy and use effective contraception throughout the duration of therapy and for 5 months following the administration of the last dose. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Evinacumab functions by: 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. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Evinacumab belongs to the None, classified under the direct parent group Peptides. This compound is a part of the Organic Compounds, falling under the Organic Acids superclass, and categorized within the Carboxylic Acids and Derivatives class, specifically within the Amino Acids, Peptides, and Analogues subclass.

Categories:

Evinacumab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Angiopoietin-like 3 Inhibitor, Angiopoietin-like 3 Inhibitors, Antibodies, Globulins, Hypolipidemic Agents, Immunoproteins, Lipid Modifying Agents, Lipid Modifying Agents, Plain, Lipid Regulating Agents, Proteins. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Evinacumab include:

• Molecular Weight: 146000.0