Galcanezumab API Manufacturers

General Description:

Galcanezumab, identified by CAS number 1578199-75-3, is a notable compound with significant therapeutic applications. Galcanezumab is a humanized monoclonal antibody developed by Eli Lilly and Company against human calcitonin gene-related peptide (CGRP). Although several small-molecule CGRP receptor antagonists have been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to selectively bind to CGRP entities with high potency. Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability. Galcanezumab was approved by the FDA in September 2018, and is indicated for the preventive treatment of migraine and the treatment of episodic cluster headache. It is unknown if galcanezumab has an effect on pregnancy outcomes. A pregnancy exposure registry has been established to evaluate the safety of this drug in pregnant women.

Indications:

This drug is primarily indicated for: Galcanezumab is indicated in adults for the preventive treatment of migraine and the treatment of episodic cluster headache. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Galcanezumab undergoes metabolic processing primarily in: After administration, galcanezumab is expected to be degraded into small peptides and amino acids by proteolysis, in a process similar to the one followed by endogenous immunoglobulins. Galcanezumab is not believed to be metabolized by liver enzymes, making drug-drug interactions relatively unlikely. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Galcanezumab are crucial for its therapeutic efficacy: Galcanezumab follows a linear pharmacokinetic profile, with a Cmax and AUC_0-∞ considered to be dose-proportional between 1 and 600 mg. After a single dose of galcanezumab-gnlm administered subcutaneously, the time to maximum concentration was 5 days. In a group of healthy subjects (n=7) given four biweekly doses of galcanezumab, T_max was 3 days, C_max was 37,210 ng/mL and the AUC was 1,959,000 ng⋅day/mL. The injection site location does not appear to significantly influence the absorption of this drug. Galcanezumab is expected to have a subcutaneous bioavailability between 50% and 100%, similar to other monoclonal antibodies. Renal and hepatic impairment are not expected to have an effect on the pharmacokinetics of galcanezumab. A population analysis has shown that pharmacokinetic parameters are not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), while body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Galcanezumab is an important consideration for its dosing schedule: Between 1 and 600 mg of galcanezumab, the mean serum half-life ranged from 25 to 30 days. On average, the elimination half-life of galcanezumab was approximately 27 days. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Galcanezumab exhibits a strong affinity for binding with plasma proteins: Readily accessible data regarding the protein binding of galcanezumab is not available. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Galcanezumab from the body primarily occurs through: Monoclonal antibody agents like galcanezumab are generally eliminated via intracellular catabolism, followed by fluid-phase or receptor-mediated endocytosis. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Galcanezumab is distributed throughout the body with a volume of distribution of: The apparent volume of distribution of galcanezumab is 7.3 L, with 34% inter-individual variability. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Galcanezumab is a critical factor in determining its safe and effective dosage: The apparent clearance of galcanezumab is 0.008 L/h. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Galcanezumab exerts its therapeutic effects through: Galcanezumab is administered as a subcutaneous injection. During clinical trials, it was noted that galcanezumab therapy significantly reduced the mean number of migraine headache days and a good tolerability profile. Additionally, post hoc efficacy analyses showed that 32% of patients given galcanezumab responded to treatment, compared to 18% in the placebo group. Hypersensitivity reactions, including dyspnea, urticaria, and rash, have been reported in patients using galcanezumab. Cases of anaphylaxis and angioedema have also been reported in the postmarketing setting. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Galcanezumab functions by: Galcanezumab is a humanized monoclonal antibody that targets and binds calcitonin gene-related peptide (CGRP). Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy. Also, research has shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients. For these reasons, binding to CGRP to interfere with its activity was specifically designed as the mechanism of action for galcanezumab, in order to reverse the migraine-inducing activity of natural CGRP. By binding to natural endogenous CGRP, galcanezumab interferes with its activities by making it unable to bind to CGRP receptors. Moreover, studies have shown that humanized monoclonal antibodies against CGRP have successfully reduced the frequency of migraine headaches in early clinical trials as a preventative therapeutic. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Galcanezumab 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:

Galcanezumab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Analgesics, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, 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 Galcanezumab include:

• Molecular Weight: 147000.0