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Emgality ® (galcanezumab-gnlm) injection100 mg/mL, 120 mg/mL
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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.
Mechanism of Action of Galcanezumab
Galcanezumab is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody (mAb) that
Galcanezumab targets CGRP and binds with high
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
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