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Advances in CGRP therapeutic targets for migraine: where do we stand 5 years later?
Journal article   Peer reviewed

Advances in CGRP therapeutic targets for migraine: where do we stand 5 years later?

Adriana Della Pietra and Andrew F Russo
Expert opinion on therapeutic targets, Vol.30(5), pp.437-450
05/04/2026
DOI: 10.1080/14728222.2026.2671693
PMID: 42096294

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Abstract

The past five years of success with calcitonin gene-related peptide (CGRP) based drugs has transformed migraine into a relatively treatable neurological disorder. There are now eight monoclonal antibodies and small-molecule receptor antagonists available for the acute and preventive treatment of migraine. However, while the drugs have been remarkably effective and safe so far, they do not work for everyone, and some adverse effects have become apparent. We describe key developments with the CGRP therapeutics regarding real-world effectiveness and safety. Emerging evidence supporting combinatorial treatment strategies within the CGRP drugs and with onabotulinumtoxinA will be discussed. The future of peptides is bright for migraine therapeutics. A monoclonal antibody against pituitary adenylate cyclase - activating polypeptide (PACAP) has shown promise in a clinical trial and evidence suggests that CGRP and PACAP therapeutics may be complementary. A second CGRP receptor, AMY , which is also activated by another peptide, amylin, is a new therapeutic target validated by clinical and preclinical data. Building on the CGRP story, centrally acting CGRP antagonists are an untapped area that should be explored. We close with a brief speculation on possible future applications of CGRP drugs for other disorders.
 Hypertension gepant migraine PACAP cluster headache amylin monoclonal antibody CGRP onabotulinumtoxina

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