Galcanezumab is a humanized IgG4 monoclonal antibody produced in Chinese Hamster Ovary (CHO) cells by using recombinant DNA technology. It is composed of two identical immunoglobulin kappa light chains and two identical immunoglobulin gamma heavy chains with an overall molecular weight of approximately 147 kDa. It has been approved by the FDA for the prevention of migraine. 

Pharmacological class: Monoclonal antibody (mAb)

• Migraine 

Galcanezumab targets CGRP and blocks the binding of CGRP to the CGRP receptor. CRGP receptor is expressed mainly in the central nervous system, peripheral nervous system and cardiovascular system. CGRP is potent, and an increase in serum or plasma levels can lead to painful syndromes such as migraine headaches.

Usual Adult Dose for Migraine

240 mg loading dose administered as two consecutive injections of 120 mg each), followed by monthly doses of 120 mg. It should be administered in the abdomen, thigh, back of the upper arm, or buttocks subcutaneously.

Absorption: Galcanezumab achieves a maximum concentration in about five days following a subcutaneous dose. Injection site location did not influence the absorption of galcanezumab

Distribution (Vd): The apparent volume of distribution (V/F) of galcanezumab is 7.3 l

Metabolism: Galcanezumab is metabolised by catabolic pathways into small peptides and amino acids in the same manner as endogenous IgG

Route of elimination: It is generally not eliminated via hepatic, renal, or biliary pathways

Half-life: The mean serum half-life of galcanezumab is about 25-30 days. whereas the elimination half-life of galcanezumab is approximately 27 days

Clearance: The apparent clearance (CL/F) of galcanezumab is 0.008 L/h

• It is contraindicated in patients with severe hypersensitivity to galcanezumab or any of its excipients 

• Cytochrome P450 enzymes do not metabolize galcanezumab; therefore, interactions with concomitant medications that are inhibitors, substrates, or inducers of cytochrome P450 enzymes are unlikely.

• Common adverse effects associated with galcanezumab use include headache, nasopharyngitis, hematuria, and contact dermatitis
• Additional frequently reported adverse effects were diarrhoea, toothache, and increased alanine aminotransferase (ALT)

• It can lead to a severe hypersensitivity reaction. If hypersensitivity occurs, discontinue administration and initiate appropriate therapy
  
• Weigh the potential benefits against the potential risks before taking galcanezumab medication while breastfeeding

A Phase 3, randomized, double-blind, placebo-controlled study was conducted in patients with chronic migraine to evaluate effectiveness in patients who have failed ≥2 and ≥one prior migraine preventives for efficacy and safety reasons, and in those who never failed.

Patients were randomized to receive galcanezumab 120 mg/240 mg once monthly and placebo during a double-blind treatment period lasting three months. Outcomes such as number of monthly migraine headache days, change in number of monthly migraine headache days with acute medication use proportion of patients with ≥50% and ≥75% response (reduction in monthly migraine headache days),and change in patient functioning per Migraine-Specific Quality of Life Questionnaire Role Function Restrictive (MSQ RF-R) domain score were assessed from baseline.

Treatment with galcanezumab resulted in significant improvements in the number of monthly migraine headache days in patients with prior failures from baseline. Similar significant results were observed for reductions in acute medication use, improvements in MSQ RF-R domain score and ≥50% and ≥75% response rates. Results were statistically significant for the 120 mg group on the reduction in migraine headache days with acute medication use and the 240 mg galcanezumab group on all outcome measures.

In conclusion, galcanezumab was efficacious in reducing monthly migraine headache days and several other key outcomes in patients with chronic migraine in comparison with placebo.

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