Atogepant reduces migraine frequency in phase 3 trial

Various doses of the investigational agent atogepant, an orally administered calcitonin gene-related peptide receptor antagonist, significantly reduced mean monthly migraine days compared with placebo during a 12-week treatment period, according to phase 3 data from the ADVANCE trial released by the manufacturer.

The randomized, double-blind trial compared the safety, efficacy and tolerability of 10 mg, 30 mg and 60 mg of atogepant (AbbVie) with placebo. More than 900 patients with 4 to 14 migraine days per month were randomly assigned to one of the four treatment groups. The primary endpoint was the difference in mean monthly migraine days from baseline to the end of the 12-week treatment period.

All three doses of atogepant were associated with significant reductions in mean monthly migraine days compared with placebo, according to a press release. On average, patients experienced a decrease of 3.69 migraine days per month with the 10 mg dose, 3.86 migraine days per month with the 30 mg dose, and 4.2 migraine days per month with the 60 mg dose. In contrast, patients who received placebo experienced an average decrease of 2.48 migraine days per month.

A secondary endpoint was the proportion of patients who achieved at least a 50% reduction in mean monthly migraine days. Overall, 55.6% of patients who received 10 mg, 58.7% of patients who received 30 mg, and 60.8% of patients who received 60 mg of atogepant achieved at least a 50% reduction vs. 29% of patients who received placebo.

Serious adverse events occurred in 0.9% of patients in the 10 mg dose group and the placebo group, according to the release. The most common adverse events that occurred among patients in any atogepant treatment arm included constipation (6.9% to 7.7% vs. 0.5% for placebo), nausea (4.4% to 6.1% vs. 1.8% for placebo), and upper respiratory tract infection (3.9% to 5.7% vs. 4.5% for placebo). Most of these adverse events were mild or moderate in severity and did not result in discontinuation, the release said. No hepatic safety issues were reported.

In light of these results and previous data from a phase 2/3 trial, AbbVie said the company plans on moving forward with regulatory submissions for atogepant in the United States and other countries.

“With the results from these trials, we aim to provide a safe and effective preventive treatment that offers patients and healthcare providers a simple, once daily oral treatment that works specifically by blocking CGRP receptors and preventing migraine,” Thomas J. Hudson, MD, senior vice president of research and development and chief scientific officer of AbbVie, said in a press release.