Monoclonal CGRP antibodies in migraine therapy

 

By Dr Thomas N. Ward

 

Image Credit: Neurons by geralt. CC0 Public Domain via Pixabay

 

On May 17, the FDA approved the first antibody therapy for the prevention of migraine, Aimovig (also called Erenumab), which targets the CGRP receptor. Produced in both peripheral and central neurons, CGRP is a peptide that typically spikes during a migraine, and stymying its efficacy has proven to shut down migraine headaches. This is the first such treatment for migraine headaches, from which millions of people suffer each year, and it’s uniquely effective compared to resources that have existed in the past.


The newly-approved Aimovig is one of four agents that are monoclonal CGRP antibodies; the other three are currently under study and awaiting possible approval. Unlike Aimovig, these other three agents target CGRP itself rather than the receptor to which it binds. Two of the three are injected subcutaneously, and one (eptinezumab) is given intravenously. It is unclear whether there is an advantage to blocking the receptor or targeting CGRP itself, but the studies on these drugs will give patients and clinicians a more nuanced look at migraines’ causes and treatment.

As they appear to be effective preventive therapies for migraine and cluster headache, it’s likely they will be studied for other types of disabling headache as well. Erenumab is a once monthly injection that will cost approximately $575 per month. It is given by an “auto-injector,” which means patients will be able to self-administer in the thigh, upper arm, or abdomen. Patients with frequent migraine have approximately a 1 in 2 chance of a 50% reduction in their headache frequency, and a 1 in 3 chance of a 75% or greater reduction. So far, the drug appears to be very well tolerated with few side effects – an undoubted benefit for those patients who experience persistent headache. Common side effects seen with other preventive agents, such as cognitive problems or weight gain, are also not likely to occur. However the long term safety is not yet known.

CGRP has been known to be an important molecule in the pathogenesis of migraine and cluster headache for many years.  Unlike older agents for headache treatment, which sometimes constrict blood vessels, agents which block the effects of CGRP do not cause vasoconstriction. These newer agents appear to be safe even in patients with vascular diseases such as peripheral vascular disease and angina. (Read more about CGRP and its relevence in migraine treatment with this freely available chapter.)

No one treatment is a “magic bullet” for headache. There is nothing that is effective for every patient. However, for patients with frequent and disabling migraines, monoclonal CGRP antibodies provide another promising option without the need to take medication every day. The last major breakthrough for patients with “chronic migraine” occurring 15 or more days per month was Botox® which was approved in November 2010, nearly a decade ago. Interestingly, one mechanism by which Botox ® may work is by lowering systemic CGRP levels. It is clear that the ongoing research into innovative therapies for refractory headache could provide renewed hope for the millions of patients who suffer.

 


Thomas N. Ward, MD, is an Active Emeritus Professor of Neurology at the Geisel School of Medicine at Dartmouth and the editor-in-chief of the journal Headache: The Journal of Head and Face Pain. He is also the president of the Headache Cooperative of New England.

He is the co-author of Understanding Your Migraines: A Guide for Patients and Families (OUP, 2017)
 

 

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