full results from a phase 3 trial suggest.
AbbVie, the company developing the oral therapy, announced topline results of the ADVANCE trial of atogepant last year. Safety results were presented in April at the 2021 annual meeting of the American Academy of Neurology.
The full results were published online Aug. 19 in the New England Journal of Medicine ahead of the upcoming target action date of the U.S. Food and Drug Administration.
The multicenter study included nearly 900 patients who were randomly assigned to receive either placebo or one of three doses of atogepant for 12 weeks. The mean number of monthly migraine days decreased by about 4 for all three doses of the active treatment, compared with a reduction of 2.5 days with placebo.
Dr. Jessica Ailani
“Overall, this study showed us that atogepant was safe and surprisingly seems to be pretty effective regardless of the dose,” said lead author Jessica Ailani, MD, director of MedStar Georgetown Headache Center and associate professor of neurology at Georgetown University, Washington.
All doses effective
The study included 873 patients with episodic migraine with or without aura. Patients who were not assigned to the placebo control group received either 10 mg, 30 mg, or 60 mg of atogepant once daily.
After a 4-week screening period, all patients received treatment for 12 weeks and then entered a 4-week safety follow-up period. In total, the participants completed eight scheduled clinical visits.
The mean reduction from baseline in the mean number of migraine days per month was 3.7 with the 10-mg dose of atogepant, 3.9 with the 30-mg dose, 4.2 with the 60-mg dose, and 2.5 with placebo. The differences between each active dose and placebo was statistically significant (P < .001).
Treatment with the CGRP inhibitor was also associated with a reduction in the mean number of headache days per month. The mean reduction from baseline was 3.9 days for the 10-mg dose, 4.0 days for the 30-mg dose, 4.2 days for the 60-mg dose, and 2.5 days for placebo (P < .001 for all comparisons with placebo).
In addition, for 55.6% of the 10-mg group, 58.7% of the 30-mg group, 60.8% of the 60-mg group, and 29.0% of the control group, there was a reduction of at least 50% in the 3-month average number of migraine days per month (P < .001 for each vs. placebo).
The most commonly reported adverse events (AEs) among patients who received atogepant were constipation (6.9%-7.7% across doses), nausea (4.4%-6.1%), and upper respiratory tract infection (1.4%-3.9%). Frequency of AEs did not differ between the active-treatment groups and the control group, and no relationships between AEs and atogepant dose were observed.
Multidose flexibility
“Side effects were pretty even across the board,” said Dr. Ailani. She noted that the reported AEs were expected because of atogepant’s mechanism of action. In addition, the rate of discontinuation in the study was low.
The proportion of participants who experienced a reduction in monthly migraine days of at least 50% grew as time passed. “By the end of this study, your chance of having a greater than 50% response is about 75%,” Dr. Ailani said.
“Imagine telling your patient, ‘You stick on this drug for 3 months, and I can almost guarantee you that you’re going to get better,’” she added.
Although the treatment has no drug-drug contraindications, drug-drug interactions may occur. “The availability of various doses would allow clinicians to adjust treatment to avoid potential drug-drug interactions,” said Dr. Ailani. “That multidose flexibility is very important.”
An FDA decision on atogepant could be made in the coming months. “I’m hopeful, as a clinician, that it is positive news, because we really have waited a long time for something like this,” Dr. Ailani said.
“You can easily identify patients who would do well on this medication,” she added.
In a different study of atogepant among patients with chronic migraine, there were recruitment delays because of the pandemic. That study is now almost complete, Dr. Ailani reported.