Promising Results for mAb Migraine Treatment Targeting PACAP Reported in NEJM

A single intravenous infusion of Lu AG09222 (Lundbeck, Deerfield, IL), a humanized monoclonal antibody (mAb) that targets the pituitary adenylate cyclase-activating polypeptide (PACAP) ligand, was found to be superior to placebo in reducing migraine frequency over 4 weeks. The results of a phase 2 proof-of-concept clinical study (NCT05133323) were published in The New England Journal of Medicine, highlighting a potentially effective new mechanism of action for therapies developed to treat people with migraine.

The double-blind, randomized, placebo-controlled trial included 237 adult participants aged 18 to 65 years with migraine, who experienced failure of benefit with ≥2 previous preventive treatments for migraine. There was a 4-week treatment period with 8 weeks of follow up, and participants were randomly assigned 2:1:2 to receive:

• A single infusion of Lu AG09222 at 100 mg (n=46)
• A single infusion of Lu AG09222 at 750 mg (n=97)
• Placebo (n=94)

The primary outcomes were the percentage of participants with ≥50% reduction from baseline in monthly migraine days (MMDs) and change from baseline in the number of monthly headache days (MHDs).

• In the overall population, the mean number of MMDs was 16.7, the mean number of MHDs was 17.4, and medications for treating headache were used a mean of 13.1 days per month.
• 32% of participants who received Lu AG0922 at 750 mg reached a ≥50% reduction in MMDs compared with 27% of those who received placebo.
• Participants who received Lu AG09222 at 750 mg showed a change from baseline in MMDs of -6.2 days vs -4.2 days in the placebo group (difference, -2.0 days; 95% CI, -3.8 to -0.3; P=.02).

Adverse events (AEs) were mild, and AEs with a higher incidence in the LU AG09222 group compared with those taking placebo included COVID-19, nasopharyngitis, and fatigue. The trial was completed with funding from Lundbeck.