What’s New

The newest migraine therapy to become available for general clinical use in the U.S. is zavegpant (Zavzpret), an anti-CGRP “gepant” nasal spray for the treatment of acute migraine headache that received its FDA approval in March. Zavzpret joins the triptans, Nurtec, Ubrelvy, Reynow and Trudhesa as a “designer drugs” developed specifically for acute migraine treatment, and if you have not found its predecessors to be effective, easy to tolerate, or both, Zavzpret is well worth a try. For more information regarding Zavzpret, click here and here [Spring 2023 issue/volume 18/page18].

What’s Now

Erenumab (Aimovig), the first of the once-monthly/subcutaneously self-injected anti-CGRP monoclonal antibodies (mabs) first became available in the U.S. for general clinical use in 2018, and it rapidly was joined by galcanezumab (Emgality), and fremanezumab (Ajovy). All 3 are indicated for prevention of episodic migraine or suppression of chronic migraine, and all 3 have been in widespread clinical use for up to 5 years.

If you need a prevention/suppression therapy for your migraine and you want to try a medication from this class, which of the 3 is best?

The results of a research study published in Headache, the journal of the American Headache Society, in June found that for the relevant migraine population as a whole there is no clear evidence that any one of these monoclonal antibodies may be superior to the others in effectiveness. While the side effect of constipation may be somewhat more common with Aimovig, especially at the higher of the 2 doses currently in use, all 3 medications typically are well-tolerated and effective – often rapidly so – in a majority of those patients who try one.

Analogous to the decades-long experience of migraineurs with the triptans for acute headache treatment, some patients may find that all 3 will be effective. Others may have a preference; there are reasonably good published studies suggesting that switching from one to another may yield an improved response. As the specific mechanism of action of Aimovig is somewhat different than that of Engility and Ajovy, common sense would suggest that a failure to respond to, say, Emgality, would call for a trial of Aimovig rather than a trial of Ajovy.

Still other patients may fail all 3. How can this be? If CGRP is such an important component of the biologic circuitry that generates migraine, why should treatment with a medication that disables CGRP (Emgality or Ajovy) or blocks the receptor to CGRP (Aimovig) not disable the circuitry and reduce migraine burden?

Put simply, not all migraineurs are alike, either in terms of their migraine clinically, or in terms of the underlying biology producing their migraine. For some, CGRP may be a major player. For others, maybe not so much.

What’s Coming

On the horizon are new therapies which will target other sites and chemicals in migraine’s biologic circuitry, and one of the most interesting potential targets is a protein molecule, pituitary adenylate cyclase-activating polypeptide (PACAP). It seems quite possible that migraineurs who fail to respond to anti-CGRP therapy may respond to therapies that target PACP instead.

More on this newbie, the research therapies under investigation that target PACAP and the potential for additional benefits from those therapies in our soon to be published Fall 2023 issue.