For the primary end point, the 3 dose options atogepant (AbbVie) were associated with a reduction ranging from 3.9 to 4.2 days in the mean number of headache days per month for those with episodic migraine.
With a regulatory decision expected to come late in the third quarter of 2021, AbbVie has released full results of the phase 3 ADVANCE study (NCT02848326) in the New England Journal of Medicine, reinforcing atogepant as a potential option for the preventive treatment of episodic migraine.1,2
A total of 873 patients with episodic migraine were included in the efficacy analysis and were randomized 1:1:1:1 to receive a once-daily dose of oral atogepant (10 mg, 30 mg, or 60 mg) or placebo for 12 weeks. Investigators used change from baseline in the mean number of migraine days per month as the primary end point, and headache days per month, 50% reductions in 3-month average of migraine days per month, quality of life, and scores on the Activity Impairment in Migraine-Diary (AIM-D) as key secondary end points.
Topline results previously announced in July 2020 showed that treatment with the agent met primary end point, with decreases in mean monthly headache days of 3.7, 3.9, and 4.2 days, respectively, in the 10 mg (n = 214), 30 mg (n = 223) and 60 mg (n = 222) atogepant groups compared with a 2.5-day decline in the placebo arm.3
"Too many people around the world face the incapacitating challenges of migraine, which place undue burden on patients, care partners, and health systems," Michael Gold, MD, vice president, Neuroscience Development, AbbVie, said in a statement.1 "At AbbVie, we are resolutely committed to advancing new treatment options across the migraine continuum. These data reinforce our confidence in atogepant as a potential option for the preventive treatment of migraine."
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Atogepant, a calcitonin gene-related peptide (CGRP) antagonist, demonstrated an ability to improve several prespecified, multiplicity-controlled secondary end points across the 12-week period. Those in the atogepant 10-, 30-, and 60-mg dose groups experienced decreases in mean monthly headache days of 3.9 (baseline, 8.4), 4.0 (baseline, 8.8), and 4.2 (baseline, 9.0) days vs a 2.5-day (baseline, 8.4) decline in the placebo arm (P <.0001 for all doses).
From baseline, there was a change of –3.7, –3.7, and –3.9 in the mean number of days of use of medication to treat migraine attacks per month across all 3 treatment groups, compared with –2.4 for placebo (P <.001 for all comparisons with placebo). An at least 50% reduction in the 3-month average of migraine days occurred for 55.6% of participants in the 10-mg atogepant group, 58.7% of those in the 30-mg group, 60.8% of those in the 60-mg atogepant group, and 29% for those in the placebo group (P <.001 for all comparisons with placebo).
For both the 30-mg and 60-mg dose groups, investigators observed significant greater score improvements of –2.5 points (P = .0005) and –3.3 points (P <.0001) in the mean monthly AIM-D Performance of Daily Activities domain. Similarly, patients in these dose groups also showed statistically greater improvement in the Physical Impairment domain in the AIM-D score (30-mg atogepant, –2.0 [P = .0021]; 60-mg atogepant, –2.5 [P = .0002]). On the other hand, those in the 10-mg atogepant group did not have significant differences on the Performances of Daily Activities domain of the AIM-D (difference, –1.2 [95% CI, –2.6 to 0.2]) and the score on the Physical Impairment domain of the AIM-D (difference, –1.1 [95% CI, –2.3 to 0.1).
"Migraine symptoms can vary in frequency and severity from person to person and from attack to attack, which is why they can impact people's daily lives in so many different ways," Peter J. Goadsby, MD, PhD, neurologist, University of California–Los Angeles, and study author, said in a statement.1 "The novel AIM-D functional scale administered in the ADVANCE study and the Migraine-Specific Quality of Life Questionnaire helped us monitor the effects of migraine on ability to perform daily activities and functions. These data, along with the primary endpoint and other secondary endpoints, help further our understanding of atogepant as a potential treatment option for people living with migraine."
A total of 53.9% of participants reported an adverse event (AE), with similar frequency between placebo and treatment groups. The most commonly reported AEs for those in the atogepant group were constipation (6.9%-7.7% across doses), nausea (4.4%-6.1% across doses) and upper respiratory tract infection (1.4%-3.9% across doses).
The FDA announced it had accepted AbbVie’s new drug application (NDA) for atogepant in March, with a regulatory decision expected to come late in the third quarter of this year.4 The NDA was supported by a clinical program that included nearly 2500 patients and spanned across the ADVANCE study, the pivotal phase 2b/3 study (NCT0284832), and the phase 3 long-term safety study (NCT03777059).
At the 2021 American Academy of Neurology (AAN) Annual Meeting, April 17-22, investigators presented results from ADVANCE, which included data on patient-reported outcomes, long-term safety and tolerability, and migraine-specific quality of life measures. Click below to watch Lawrence Severt, MD, PhD, director, AbbVie, discuss the robust findings and their clinical significance.