A recent phase 2 study was undertaken to investigate the safety and efficacy of a monoclonal antibody (Lu AGO9222) to pituitary adenylate cyclase-activating polypeptide (PACAP) for prevention of migraine. PACAP is a widely distributed vasodilating polypeptide, it binds to receptors in areas of the central and peripheral nervous system known to be important in the pathophysiology of migraine.

Trial participants had a substantial headache burden with a mean of 16.7 migraine days per month documented during a 4 week run in period. 2-4 previous preventative treatments had failed to provide a benefit. An infusion of the antibody, given over a period of 30 minutes, reduced the number of monthly migraine days by 6.2 days, as compared to a reduction of 4.2 days in the placebo group. Adverse events were described as mild and included nasopharyngitis and fatigue. Whilst 2 fewer days a month may be less than what was hoped, this does add up over a year to a benefit of almost one month of migraine free days from the medication.

It is always good news to have another potential treatment option for migraine. Not all patients respond to the currently available therapies, and this probably reflects the diversity of the underlying causes of migraine. This trial offers hope that future options may be of benefit to patients who are yet to find a positive response to currently available treatments.

Further trials will evaluate subcutaneous formations of the PACAP antibody, and we await their outcome with great interest.

Reference: Ashina M et al, A Monoclonal Antibody to PACAP for Migraine Prevention, N Engl J Med 2024; 391(9):855-857