PACAP and PAC1R monoclonal antibodies show mixed efficacy in early-phase migraine prophylaxis trials

Despite significant advancements in migraine prophylaxis with CGRP-targeting monoclonal antibodies and gepants, a substantial unmet need persists for patients unresponsive to current therapies. Pituitary adenylate cyclase-activating polypeptide (PACAP) and its PAC1 receptor are crucial in migraine pathophysiology, mediating neurogenic inflammation and vasodilation, making them attractive alternative targets for novel prophylactic treatments. Exploring these pathways could offer new options for patients who do not benefit from existing CGRP-based drugs, addressing a critical gap in treatment options.

This study conducted a literature review based on a PubMed search to evaluate the efficacy of monoclonal antibodies (mAbs) targeting PACAP or its PAC1 receptor as potential prophylactic treatments for migraine. The review synthesized findings from several early-phase randomized clinical trials, assessing their impact on primary endpoints such as the reduction in monthly migraine days (MMDs) compared to placebo arms. Specific trial designs, doses, and routes of administration for each mAb were extracted and summarized from the identified studies.