People with migraine who took atogepant, an orally administered calcitonin gene-related peptide (CGRP) receptor antagonist, had an average of three to four fewer migraines each month, according to findings from a phase 3, double-blind trial presented during the 2021 virtual AAN Annual Meeting.
“Atogepant is an investigational drug that is meant to reduce the frequency of migraine," said Jessica Ailani, MD, FAAN, director of MedStar Georgetown Headache Center and professor of clinical neurology in the department of neurology at Medstar Georgetown University in Washington, DC.
The agent, which is not yet available or approved by the US Food and Drug Administration, seemed to work very quickly with limited adverse events, Dr. Ailani added.
“Atogepant adds to the current available migraine preventive landscape. It allows an oral option with few side effects that can start working within weeks. This may be beneficial to many people with migraine," she told Neurology Today At the Meetings.
For 12 weeks, 910 patients received 10 mg of atogepant, 30 mg of atogepant, and 60 mg of atogepant. The cohort consisted of adults who had four to 14 migraine days each month.
Individuals who took the 10 mg dose had nearly 3.69 fewer migraine days, with the 30 mg 3.86 fewer days, and with the 60 mg dose 4.20 fewer days. Those taking placebo had 2.48 fewer migraine days.
Fifty-six percent of the cohort taking the 10 mg dose of atogepant had a greater than 50 percent decline in their three-month average of monthly migraine days; 59 percent did with 30 mg of atogepant, and 61 percent with 60 mg of atogepant compared with 29 percent for patients receiving placebo (p<0.0001 all doses).
Notably, adverse events were reported in 57 percent of participants in the placebo cohort compared with 52 to 54 percent of participants across atogepant groups. Nausea and constipation were the most commonly reported adverse events. Although none of the adverse events were serious, 3 percent of participants in the placebo group and 2 to 4 percent in the atogepant cohorts discontinued therapy as a result of adverse events.
Atogepant is similar to another CGRP antagonist, rimegepant, said Robert Cowan, MD, FAAN, professor of neurology and chief of the division of headache medicine at Stanford University, who was not involved with the study. The findings suggest “the benefits to patients with high frequency episodic migraine are likely a class effect rather than unique to any one congener," he added.
“Atogepant is still investigational, but it is encouraging to see a side effect profile and efficacy similar to rimegepant," Dr. Cowan said. “It remains too early to comment on the clinical implications as these are novel molecules that disrupt a chemical pathway whose role in health and illness is still poorly understood."
“I am intrigued by the notion that a class of drugs that has been shown effective in acute treatment does not appear to induce medication overuse when given with increased frequency. Once this is better understood, it may lend insight into the mechanisms involved in chronification of migraine," he continued.
Real-world trials are needed with more focus on genetics and phenotyping of the study cohort and head-to-head trials with standardized endpoints, he said. “Only then will clinicians be able to make informed decisions in treatment strategies."
Dr. Ailani disclosed consulting for Amgen, Abbvie, Biohaven, Eli Lilly and Company, GlaxoSmithKline, Lundbeck, Teva, Impel, Satsuma, Axsome, Vorso, Aeon, Theranica, and Medscape; providing editorial services for Current Pain and Headache Reports, Unusual Headache Syndromes, NeurologyLive, Infomedica, and SELF; receiving clinical trial grants from American Migraine Foundation, Allergan/Abbvie, Biohaven, Eli Lilly and Company, Satsuma, and Zosano; doing promotional speaking for Allergan/Abbvie, Amgen, Biohaven, Eli Lilly and Company, Lundbeck, Teva, and owning stocks for CtrM. Dr. Cowan reported consulting and serving on scientific advisory boards for Biohaven, Lilly, Amgen, Teva, and Lundbeck.
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AAN Abstract: Ailani J, Lipton R, Goadsby P, et al. Atogepant significantly reduces mean monthly migraine days in the phase 3 trial (ADVANCE) for the preventive treatment of migraine.
Neurology Today Video. Atogepant Reduces Number of Mean Monthly Migraines.