AbbVie announced results from the phase 3 ADVANCE trial evaluating oral atogepant versus placebo for the prevention of migraine. The trial met the primary endpoint of statistically significantly greater reduction in mean monthly migraine days, compared to placebo, for all doses across the 12-week treatment period. With these results, combined with prior positive Phase 2/3 trial results, AbbVie plans to move forward with regulatory submissions in the United States and other countries. Full data results will be presented at an upcoming medical congress and/or published in a peer-reviewed journal.
ADVANCE was a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial designed to evaluate the efficacy, safety, and tolerability of oral atogepant for the prevention of migraine in those with 4 to 14 migraine days per month. A total of 910 patients were randomized to one of four treatment groups evaluating 10 mg, 30 mg, or 60 mg of atogepant once daily, or placebo. Efficacy analyses were based on the modified intent-to-treat (mITT) population of 873 patients.
The primary endpoint was change from baseline in mean monthly migraine days across the 12-week treatment period. All atogepant dose groups met the primary endpoint and demonstrated statistically significantly greater decreases in mean monthly migraine days compared to placebo. Patients treated in the 10 mg/30 mg/60 mg atogepant arms experienced a decrease of 3.69/3.86/4.2 days, respectively, all compared to patients in the placebo arm, who experienced a decrease of 2.48 days.
A key secondary endpoint measured the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days across the 12-week treatment period. The trial demonstrated that 55.6%/58.7%/60.8% of patients in the 10 mg/30 mg/60 mg atogepant arms, respectively, achieved at least a 50% reduction, compared to 29.0% of patients in the placebo arm.
The most common adverse events reported with a frequency ≥ 5% in at least one atogepant treatment arm, and greater than placebo, were constipation, nausea and upper respiratory tract infection. The majority of these cases were mild or moderate in severity and did not lead to discontinuation. There were no hepatic safety issues identified in this trial.
Atogepant is an orally administered, CGRP receptor antagonist (gepant) specifically developed for the preventive treatment of migraine. CGRP and its receptors are expressed in regions of the nervous system associated with migraine pathophysiology. Studies have shown that CGRP levels are elevated during migraine attacks and selective CGRP receptor antagonists confer clinical benefit in migraine.
Migraine is a complex, chronic disease with episodic attacks that are often incapacitating and characterized by headache pain as well as neurologic and autonomic symptoms. It is highly prevalent, affecting more than one billion people worldwide, and is the highest cause of disability worldwide for people under 50 years of age.