Monoclonal antibody superior to placebo in reducing migraine frequency

Key takeaways:

• 32% in the treatment group saw at least a 50% reduction in migraine days per month vs. 27% in the placebo group.
• The treatment group had 5.8 fewer headache days per month vs. 4.1 fewer days for placebo.

In patients with difficult-to-treat migraine, IV infusion of a novel monoclonal antibody provided superior migraine frequency relief compared with placebo in as early as 4 weeks, data show.

Traditional medications for migraine prevention like propranolol and topiramate “are often discontinued owing to an inadequate response or unacceptable side effects,” Messoud Ashina, MD, professor of neurology in the faculty of health and medical sciences at the University of Copenhagen, and colleagues wrote in The New England Journal of Medicine.

“More recently developed therapeutics include monoclonal antibodies and small-molecule receptor antagonists that target the signaling molecule calcitonin gene-related peptide,” they added. “However, 40% to 70% of persons with migraine do not have a sufficient benefit from the CGRP-targeted medications, which underscores the pressing need for new mechanism-based therapeutic agents.”

Prior evidence suggests that targeting pituitary adenylate cyclase-activating polypeptide (PACAP) may be a promising method for migraine treatment, according to the researchers. So, they sought to examine safety and efficacy of Lu AG09222, a humanized monoclonal antibody and IV therapy that targets the PACAP ligand, in a phase 2a, double-blind, randomized, placebo-controlled trial.

The HOPE study was conducted across 25 centers in Europe and North America and included 237 adults (100% white, 88% women) with migraine for whom two to four prior preventive treatments failed. Patients were randomly assigned 2:1:2 to receive a single-dose baseline infusion of 750 mg of Lu AG09222, 100 mg of Lu AG09222 or placebo. The trial, which required all participants to keep a daily electronic headache diary, included a 4-week treatment period and an 8-week follow-up interval.

The primary endpoint was mean change from baseline in the number of migraine days per month during weeks 1 through 4 between the 750 mg treatment cohort compared with those given placebo. Exploratory endpoints included the mean change in total number of monthly migraine attacks and mean change from baseline in number of days requiring medicinal intervention from weeks 1 to 4 in the 750 mg group compared with placebo, along with similar assessments in the 100 mg treatment group.

Results showed that the mean change from baseline in the number of migraine days over weeks 1 through 4 was 6.2 days in the 750 mg treatment group compared with 4.2 days in the placebo group (95% CI, 3.8 to 0.3).

The researchers wrote that the percentage of participants who logged at least a 50% reduction from baseline in migraine days per month was 32% for the 750 mg group and 27% in the placebo group. Additionally, the mean change in the number of headache days per month from weeks 1 to 4 was 5.8 days in the high-dose treatment group and 4.1 days in the placebo group.

Adverse events were classified as mild, with the most common being COVID-19, nasopharyngitis and fatigue, according to the researchers. Only one serious adverse event was recorded in the treatment group 1 month following infusion, but it was deemed unrelated to the treatment.

“These findings affirm the proof of concept, showing that inhibition of PACAP signaling by Lu AG09222 represents a new and potentially effective mechanism for migraine prevention,” Ashina and colleagues wrote.