Phase 2 Data results promising: Monoclonal Antibody Lu AG09222 Reduces Migraine Days Significantly Over Placebo

"A single intravenous infusion of 750 mg of Lu AG09222 demonstrated a significant reduction in migraine frequency compared to placebo over the following four weeks," the researchers wrote in the New England Journal of Medicine.

Migraine sufferers often face debilitating symptoms, including intense headaches, nausea, and sensitivity to light and sound. Current treatments offer varying degrees of relief, but many patients continue to experience frequent and severe attacks. The introduction of new preventive therapies is, therefore, a crucial area of research.

Targeting pituitary adenylate cyclase-activating polypeptide represents a novel approach to migraine treatment. Therefore, Messoud Ashina, University of Copenhagen (M.A.), Copenhagen, Denmark, and colleagues aimed to determine the safety and efficacy of intravenous Lu AG09222, a humanized monoclonal antibody directed against the PACAP ligand, for migraine prevention.

For this purpose, the researchers conducted a Phase 2, double-blind, randomized, placebo-controlled trial involving adult participants aged 18 to 65 who had experienced insufficient benefit from two to four prior preventive migraine treatments. The trial featured a 4-week treatment period followed by an 8-week follow-up.

Participants were randomly assigned in a 2:1:2 ratio to receive either a single intravenous infusion of 750 mg of Lu AG09222, 100 mg of Lu AG09222, or a placebo. The primary endpoint was the mean change from baseline in the number of migraine days per month during the first four weeks, specifically comparing the 750-mg Lu AG09222 group with the placebo group.

The researchers reported the following findings:

• Of 237 participants enrolled, 97 received 750 mg of Lu AG09222, 46 received 100 mg of Lu AG09222, and 94 received placebo.
• The mean number of baseline migraine days per month was 16.7 in the overall population, and the mean change from baseline over weeks 1 through 4 was −6.2 days in the Lu AG09222 750-mg group, compared with −4.2 days in the placebo group.
• Adverse events with a higher incidence in the Lu AG09222 750-mg group than in the placebo group during the 12-week observation period included coronavirus disease 2019 (7% versus 3%), nasopharyngitis (7% versus 4%), and fatigue (5% versus 1%).

"If successful, Lu AG09222 could represent a significant advancement in migraine therapy, offering hope for those seeking more effective solutions to manage their condition," the researchers concluded.

Reference:

DOI: 10.1056/NEJMoa2314577