AAN 2026 | PACAP in migraine pathophysiology and emerging therapeutic agents targeting this peptide
Peter Goadsby, MD, PhD, DSc, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia, discusses the role of pituitary adenylate cyclase activating polypeptide (PACAP) as an emerging therapeutic target in migraine. He highlights clinical findings with bocunebart, a PACAP-targeting antibody that reduced monthly migraine days in Phase II studies, and reviews ongoing efforts to develop new PACAP-based migraine therapies. This interview took place at the 78th American Academy of Neurology (AAN) Annual Meeting in Chicago, IL.
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Transcript
Pituitary adenylate cyclase activating polypeptide or PACAP to its friends is a 38 amino acid, at least in mammals, polypeptide that has a role in migraine as evidenced by the fact that you can trigger a migraine attack with its infusion, that its levels are elevated during migraine in humans, and that this can be normalized with a triptan. This led investigators to pursue targets at the PACAP receptors or PACAP, the peptide itself, as treatments for migraine...
Pituitary adenylate cyclase activating polypeptide or PACAP to its friends is a 38 amino acid, at least in mammals, polypeptide that has a role in migraine as evidenced by the fact that you can trigger a migraine attack with its infusion, that its levels are elevated during migraine in humans, and that this can be normalized with a triptan. This led investigators to pursue targets at the PACAP receptors or PACAP, the peptide itself, as treatments for migraine. The most advanced of the therapies is a peptide called bocunebart. If you haven’t heard the name, it is a new naming system that the WHO has introduced. And there were two studies with bocunebart, which is a pituitary adenylate cyclase activating polypeptide PACAP antibody. So it binds to the peptide itself. First one was published in the New England Journal of Medicine about two years ago and showed in a Phase IIa study that bocunebart was able to reduce the frequency of migraines, a mixed group of episodic and chronic migraine with a baseline at about 17 days, and were able to reduce the number of attacks by 6.2 days at the 750 milligram dose. So it was effective against placebo. The second study has been reported, it’s called PROCEED, and it’s been reported only in press release to be positive at its primary endpoint of reducing monthly migraine days over the 12 weeks for the intravenous formulation. So for PACAP, it’s watch this space. We’ll see more studies. We may see people develop or companies develop approaches, treatments, or even small molecules to the individual receptors. There are four receptors, probably worth saying. The PAC1 receptor, which only PACAP is active at, and the two VPAC receptors, VPAC1 and VPAC2, which are shared with VIP and another receptor shared with VIP called MRGPRX2. We don’t have any immediately available therapeutic targets for those. Pretty exciting. PACAP is probably the next big thing.
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