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  1. Medical Information Right
  2. Neuroscience Right
  3. Emgality (galcanezumab-gnlm) injection Right
  4. What is the mechanism of action of Emgality® (galcanezumab-gnlm) in migraine prevention?
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Emgality ® (galcanezumab-gnlm) injection

100 mg/mL, 120 mg/mL

Full Prescribing Information

This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.

What is the mechanism of action of Emgality® (galcanezumab-gnlm) in migraine prevention?

Emgality (galcanezumab) is a humanized IgG4 mAb that binds CGRP and prevents its biological activity without blocking the CGRP receptor.

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US_cFAQ_GLC004_MOA_MIGRAINE
en-US

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).4,5

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.5

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.5

In the phase 3, double-blind, placebo-controlled migraine prevention studies,6-8 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.2,5

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.9-11

See Galcanezumab Mechanism of Action Video: http://www.kaltura.com/tiny/0f8le  for a video illustrating the mechanism of action of galcanezumab.

Galcanezumab Mechanism of Action Video: http://www.kaltura.com/tiny/0f8le