Erenumab API Manufacturers

General Description:

Erenumab, identified by CAS number 1582205-90-0, is a notable compound with significant therapeutic applications. Erenumab (AMG-334) (INN; trade name Aimovig) is a human monoclonal antibody designed specifically to bind and antagonize the calcitonin gene-related peptide receptor (CGRPR) as a means to prevent migraines. Aimovig, as released and marketed by Novartis and Amgen, is in fact a novel therapeutic approach as the first and only FDA approved treatment specifically developed to prevent migraine by blocking the CGRP receptor, which is believed to play a critical role in migraine . In particular, erenumab-aooe is a human immunoglobulin G2 monoclonal antibody that has high affinity binding to the CGRP receptor . The antibody is produced utlilizing recombinant DNA technology in Chinese hamster ovary cells . It is composed of 2 heavy chains, each containing 456 amino acids, and 2 light chains of the lambda subclass, each containing 216 amino acids, with an approximate molecular weight of 150 kDa .

Indications:

This drug is primarily indicated for: Erenumab is indicated for the preventative treatment of migraine in adults . Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Erenumab undergoes metabolic processing primarily in: Erenumab CGRP antibodies demonstrate a low risk for drug-drug interactions and hepatotoxicity since they are predominantly metabolized by degradation into peptides and single amino acids . This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Erenumab are crucial for its therapeutic efficacy: Following a single subcutaneous dose of 70 mg or 140 mg erenumab administered to healthy adults, the median peak serum concentrations were attained in about 6 days, and the estimated absolute bioavailability was approximately 82% . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Erenumab is an important consideration for its dosing schedule: Erenumab exhibits non-linear kinetics as a result of binding to the CGRP receptor . Lower than 2-fold accumulation was recorded in trough serum concentrations (Cmin) for episodic and chronic migraine patients following subcutaneous administration of 70 mg once-monthly and 140 mg once-monthly doses . Serum trough concentrations approached steady state by 3 months of dosing . The effective half-life of erenumab was observed to be 28 days . This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Erenumab exhibits a strong affinity for binding with plasma proteins: Readily accessible data regarding the protein binding of erenumab is not available, although it is reported that erenumab is capable of 50% to 99% total inhibition of calcitonin gene-related peptide receptors with dosages of 255 ng/mL and 1134 ng/mL, respectively . This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Erenumab from the body primarily occurs through: Two elimination phases are observed for erenumab. At low concentrations, the elimination is mainly through saturable binding to target (CGRP receptor), while at higher concentrations the elimination of erenumab is primarily through a non-specific, non-saturable proteolytic pathway . These phases correspond to studies that demonstrated two parallel elimination pathways: (a) a slow non-specific elimination pathway through the hepatic reticuloendothelial system, and (b) a rapid saturable elimination pathway mediated by degradation or internalization of the erenumab-receptor complex . Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Erenumab is distributed throughout the body with a volume of distribution of: After a single 140 mg intravenous dose, the mean (SD) volume of distribution during the terminal phase (Vz) was estimated to be approximately 3.86 (0.77) L . This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Erenumab is a critical factor in determining its safe and effective dosage: Certain studies show that the population estimate of linear clearance is independent of erenumab concentrations and stays approximately constant at 0.214 L/day (95% CI: 0.191–0.243) . In contrast, the nonlinear clearance is dependent on the target receptor density and the amount of erenumab bound to the receptors . Nevertheless, the maximal nonlinear clearance was observed to be about 1.84L/day . It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Erenumab exerts its therapeutic effects through: As a human monoclonal antibody designed to specifically bind with and antagonize the calcitonin gene-related peptide (CGRP) receptor, there is the possibility that erenumab could interfere with natural activities of CGRP that may not be immediately or directly associated with migraines. For example, at peripheral synapses, CGRP released from trigeminal terminals results in vasodilation by way of CGRP receptor on smooth muscle cells of meningeal and cerebral blood vessels, making CGRP a potent general arterial vasodilator . Antagonism of CGRP receptors responsible for such vasodilation could theoretically result in vasoconstriction and raises in blood pressure. In a randomised, double-blind, placebo-controlled study in healthy volunteers, concomitant administration of erenumab (140 mg intravenous, single dose) with sumatriptan (12 mg subcutaneous, given as two 6 mg doses separated by one hour) had no effect on resting blood pressure compared with sumatriptan alone, however . Please note that erenumab is indicated for subcutaneous use only, though . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Erenumab functions by: Erenumab is a human monoclonal antibody that has been designed to bind specifically to the calcitonin gene-related peptide (CGRP) receptor and antagonize the CGRP receptor function . Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy . Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients . For all these reasons, the binding and antagonism of CGRP receptors was designed to be mechanism of action for erenumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. CGRP and its receptor are expressed in both the peripheral and the central nervous system . In addition to playing a role in cranial nociception, CGRP is also a potent general arterial vasodilator . At peripheral synapses, CGRP released from trigeminal terminals results in vasodilation via CGRP receptors on the smooth muscle cells of meningeal and cerebral blood vessels . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Erenumab 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:

Erenumab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Analgesics, Antibodies, Antibodies, Monoclonal, Antimigraine Preparations, Blood Proteins, Calcitonin Gene-Related Peptide (CGRP) Antagonists, Calcitonin Gene-Related Peptide Receptor Antagonists, Central Nervous System Agents, Globulins, Immunoglobulins, Immunoproteins, Nervous System, Peripheral Nervous System Agents, Proteins, Sensory System Agents, Serum Globulins. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Erenumab include:

• Molecular Formula: C6472H9964N1728O2018S50