Emerging experimental drugs in clinical trials for migraine: observations and key talking points

INTRODUCTION: There have been significant advances in the treatment of migraine. In response to the clinical success of monoclonal antibodies targeting calcitonin gene-related peptide, there is interest in the clinical trial outcomes of alternative emerging drugs that act on novel targets associated with migraine pathophysiology. As approximately 50% of patients do not respond to CGRP therapies, there is significant value in future drug innovation. Emerging drugs in clinical trials for the treatment of migraine aim to fill this need. AREAS COVERED: The emerging drugs that will be discussed in this review include zavegepant, lasmiditan, delta opioid receptor agonists, neuronal nitric oxide synthase inhibitors, monoclonal antibodies targeting pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor, dual orexin receptor antagonists, metabotropic glutamate receptor 5 antagonists, and inducers of ketosis. EXPERT OPINION: When considering the preclinical and clinical research related to the emerging drug classes discussed in this review, most therapies are derived from highly supported targets of migraine pathogenesis. Although the individual drugs discussed in this review may be of dubious clinical value, the importance of the therapeutic targets on which they act cannot be understated. Future research is necessary to appropriately target the pathways elucidated by preclinical studies.