Emgality® (Galcanezumab)

Para consultar la información para prescribir completa de Emgality® (Galcanezumab) de clic en el siguiente enlace: Información para prescribir

La información es proporcionada en respuesta a su solicitud, y puede contener datos relacionados a dosis, usos, formulaciones y poblaciones diferentes a la Información para Prescribir del producto. Consulte la Información para Prescribir en la liga que aparece arriba.

What is the mechanism of action of galcanezumab in migraine prevention?

Galcanezumab is a humanized IgG4 mAb that binds CGRP and prevents its biological activity without blocking the CGRP receptor.


The information contained in this letter may not completely match the current local labeling for GALCANEZUMAB. Please see local labeling approved in your country.

Mechanism of Action of Galcanezumab

Galcanezumab is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody (mAb) that

  • binds calcitonin gene-related peptide (CGRP), and
  • prevents its biological activity without blocking the CGRP receptor.1,2

Galcanezumab targets CGRP and binds with high

  • affinity (dissociation constant [KD] 31 pM), and3,4
  • specificity (>10,000-fold vs related peptides adrenomedullin, amylin, calcitonin, and intermedin).1,4

When galcanezumab is administered, the premise is that

  • CGRP will bind to galcanezumab, and
  • the amount of free CGRP that is available to interact with the CGRP receptors will be reduced.1

Galcanezumab-bound CGRP is expected to take on the disposition characteristics of galcanezumab resulting in

  • a lower clearance than free CGRP, and
  • an increase in total CGRP concentration upon galcanezumab administration.1

In the phase 3, double-blind, placebo-controlled migraine prevention studies,5-7 total CGRP concentrations increased after galcanezumab administration compared to placebo. This indicated that the antibody was

  • binding to CGRP, and
  • slowing the clearance of the CGRP that was bound to the antibody.1,2

The binding of galcanezumab to CGRP is slowly reversible based on the off-rate for the CGRP/galcanezumab interaction determined experimentally. However, any released CGRP is likely to be quickly bound to the same or a different antibody based on the rapid on-rate for binding.4

Being a macromolecule, galcanezumab does not appreciably cross the blood-brain barrier. Therefore, it is thought that galcanezumab acts peripherally in structures involved in migraine pathogenesis, including the trigeminal ganglia.8-10

See Galcanezumab Mechanism of Action Video: https://www.kaltura.com/tiny/mze6e  for a video illustrating the mechanism of action of galcanezumab.

Galcanezumab Mechanism of Action Video: https://www.kaltura.com/tiny/mze6e 

The Role of Calcitonin Gene-Related Peptide in Migraine


  • a 37-amino acid peptide commonly found in the peripheral and central nervous systems, and
  • considered a potent vasodilator in both the peripheral and cerebral vasculature.11,12

It has a potency approximately

  • 10 times higher than the most potent prostaglandins, and
  • 10 to 100 times greater than acetylcholine and neuropeptide substance P.11

The CGRP neuropeptide has a wide range of physiological actions including cardiovascular regulatory processes and other conditions including but not limited to neurogenic inflammation, pain, and migraine. Migraine pathogenesis is thought to be associated with the activation of the trigeminovascular system. CGRP is distributed throughout the trigeminovascular system and is released from trigeminal ganglia nerves upon activation.11

The role of CGRP in migraine has been underscored by several experimental and clinical findings including

  • an increase of jugular CGRP venous blood concentration during spontaneous migraine attacks
  • intravenous (IV) infusion of recombinant human CGRP triggered a migraine attack in migraine sufferers
  • elevated CGRP serum concentrations were inhibited by triptan treatment, and
  • small-molecule CGRP receptor antagonists were effective in relieving acute migraine headache in double-blind, randomized, placebo-controlled trials.3,12,13

The CGRP neuropeptide exists as α-CGRP and β-CGRP. The α-CGRP form is primarily associated with sensory neurons and is thought to have a major role in the pathogenesis of migraine headache.8,11,14

See The Role of CGRP in Migraine: https://www.kaltura.com/tiny/u8dls for a video explaining the role of CGRP in migraine.

The Role of CGRP in Migraine: https://www.kaltura.com/tiny/u8dls