A Monoclonal Antibody to PACAP for Migraine Prevention

This phase 2, double blind, randomized, placebo-controlled trial evaluated the efficacy and safety of Lu AG09222, a humanized monoclonal antibody targeting pituitary adenylate cyclase activating polypeptide (PACAP), for migraine prevention. Participants (18–65 years) with a history of 2–4 failed preventive treatments received a single intravenous infusion of 750 mg Lu AG09222, 100 mg Lu AG09222, or placebo. The primary endpoint was the mean change in migraine days per month over weeks 1–4. Results showed a significant reduction in migraine days with the 750-mg dose (−6.2 days) compared to placebo (−4.2 days; difference −2.0 days, 95% CI −3.8 to −0.3; P=0.02). Adverse events included COVID-19, nasopharyngitis, and fatigue. The study supports PACAP inhibition as a novel mechanism for migraine prevention, warranting further investigation.

This phase 2, double blind, randomized, placebo-controlled trial evaluated the efficacy and safety of Lu AG09222, a humanized monoclonal antibody targeting pituitary adenylate cyclase activating polypeptide (PACAP), for migraine prevention. Participants (18–65 years) with a history of 2–4 failed preventive treatments received a single intravenous infusion of 750 mg Lu AG09222, 100 mg Lu AG09222, or placebo. The primary endpoint was the mean change in migraine days per month over weeks 1–4. Results showed a significant reduction in migraine days with the 750-mg dose (−6.2 days) compared to placebo (−4.2 days; difference −2.0 days, 95% CI −3.8 to −0.3; P=0.02). Adverse events included COVID-19, nasopharyngitis, and fatigue. The study supports PACAP inhibition as a novel mechanism for migraine prevention, warranting further investigation.