New England Journal of Medicine Publishes 12-Week Results from Study Evaluating Atogepant for the Preventive Treatment of Migraine
- Study also found the majority of atogepant-treated participants achieved at least a 50% reduction in mean monthly migraine days for all doses compared to placebo as a secondary endpoint¹
- Atogepant 30 mg and 60 mg doses demonstrated statistically significant improvements in all six prespecified, multiplicity-controlled secondary endpoints, including reduction in acute medication use and function impairment measures, compared to placebo¹
- Atogepant is currently under review by the U.S. Food and Drug Administration with a regulatory decision anticipated in late Q3 2021 AbbVie (NYSE: ABBV) today announced that the New England Journal of Medicine (NEJM) has published 12-week results from the Phase 3 ADVANCE trial evaluating atogepant for the preventive treatment of migraine in adults who meet criteria for episodic migraine. The study, which enrolled adult participants experiencing 4 to 14 migraine days per month, found that all active treatment arms of atogepant – 10 mg, 30 mg, and 60 mg once-daily doses – met their primary endpoint of a statistically significant reduction in mean monthly migraine days across the 12-week treatment period compared to placebo.2 The study also found that a greater proportion of atogepant-treated participants achieved at least a 50% reduction in mean monthly migraine days for all doses compared to placebo and met other key secondary endpoints.2
The full NEJM article is available at nejm.org.
Atogepant, which is currently under review by the U.S. Food and Drug Administration (FDA), is an investigational orally administered calcitonin gene-related peptide (CGRP) receptor antagonist (gepant), which, if approved, will be the first and only oral gepant specifically developed for the preventive treatment of episodic migraine.3
"Too many people around the world face the incapacitating challenges of migraine, which place undue burden on patients, care partners, and health systems," said Michael Gold, M.D., vice president, neuroscience development, AbbVie. "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."
The primary endpoint for the ADVANCE trial was change from baseline in mean monthly migraine days across the 12-week treatment period.1 All atogepant dose groups met the primary endpoint and demonstrated statistically significant reductions in mean monthly migraine days compared to placebo.1 Patients treated in the 10 mg, 30 mg, and 60 mg atogepant arms experienced a decrease of 3.7, 3.9, and 4.2 days respectively compared to patients in the placebo arm, who experienced a decrease of 2.5 days (all dose groups versus placebo, p<0.0001).1
Efficacy results for prespecified, multiplicity-controlled secondary endpoints in the ADVANCE trial across the 12-week treatment period include1:
- Patients treated with 10 mg, 30 mg, and 60 mg doses of atogepant experienced a decrease in mean monthly headache days of 3.9 (baseline 8.4), 4.0 (baseline 8.8), and 4.2 (baseline 9.0) days respectively versus a 2.5-day (baseline 8.4) decline in the placebo arm (p<0.0001 for all doses).
- A significantly greater reduction from baseline in acute medication use days was seen with all doses of atogepant compared to placebo, with a decrease of 3.7, 3.7, and 3.9 days for the 10 mg, 30 mg, and 60 mg doses respectively compared to a 2.4-day decrease with placebo (p<0.0001 for all doses).
- Across the 12-week treatment period, the trial demonstrated that 55.6%, 58.7%, and 60.8% of patients in the 10 mg, 30 mg, and 60 mg atogepant arms respectively achieved a 50% or greater reduction in monthly migraine days, compared to 29.0% of patients in the placebo arm (all dose groups versus placebo, p<0.0001).
- Improvements in the Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ v2.1) Role Function-Restrictive domain score were significantly greater with atogepant at all doses (9.9, 10.1, and 10.8 point improvements, p<0.0001 for all doses) compared to placebo at week 12.*
- Significant greater improvements in the mean monthly AIM-D** Performance of Daily Activities domain score compared to placebo were observed for the 30 mg and 60 mg doses, -2.5 points for the 30 mg dose (p=0.0005), and -3.3 points for the 60 mg dose (p<0.0001).***
- Similar to the Performance of Daily Activities domain, the Physical Impairment domain in the AIM-D score showed statistically greater improvement for the 30 mg and 60 mg doses of atogepant compared to placebo, -2.0 for the 30 mg dose (p=0.0021) and -2.5 for the 60 mg dose (p=0.0002).***
"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," said Peter Goadsby, M.D., neurologist and professor at University of California (Los Angeles) and King's College, London, and an author of the atogepant ADVANCE study NEJM article. "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."
All doses were well tolerated. The most common adverse events reported with a frequency ≥ 5% in at least one atogepant treatment arm, and greater than placebo, were constipation (6.9-7.7% across all doses versus 0.5% for placebo), nausea (4.4-6.1% across all doses versus 1.8% for placebo), and upper respiratory tract infection (3.9-5.7% across all doses versus 4.5% for placebo). The majority of cases of constipation, nausea, and upper respiratory tract infection were mild or moderate in severity and did not lead to discontinuation.1
About the Phase 3 ADVANCE Study
The pivotal Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the efficacy, safety, and tolerability of oral atogepant for the preventive treatment 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, and 60 mg of atogepant once daily, or placebo. Efficacy analyses were based on the modified intent-to-treat (mITT) population of 873 patients.
The study results were previously announced in a July 2020 press release and first presented at the 2020 Virtual Migraine Trust International Symposium and most recently during the Clinical Trials Plenary Session of the 2021 American Academy of Neurology Annual Meeting.
*MSQ v2.1 measures health-related quality of life impairments attributed to migraine for three domains: Role Function-Restrictive, Role Function-Preventive, and Emotional Function domain. A higher score indicates a lesser impact of migraine on daily activities.
**The Activity Impairment in Migraine-Diary (AIM-D) is an 11-item daily diary measure that assesses the impact of migraine on the Performance of Daily Activities and Physical Impairment. The AIM-D domain scores range between 0 to 100; higher scores indicate greater impact of migraine, and score reductions from baseline indicate improvement.
***The 10 mg dose improvements were not statistically significant.
Migraine is a complex, chronic disease with recurrent attacks that are often incapacitating and characterized by headache pain as well as neurologic and autonomic symptoms.4 It is highly prevalent, affecting more than 1 billion people worldwide, including 39 million people in the U.S. alone,5 and is the highest cause of disability worldwide for people under 50 years of age.6,7 Due to the unpredictability and fluctuation of attack frequency and severity, migraine substantially impacts many aspects of an individual's life both during and between attacks. Daily activities, work, school, and personal relationships can be negatively affected, leading to a significant burden on the person with migraine, their family, friends, employers, and healthcare systems.
Atogepant is an investigational 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. Atogepant is currently under review by the U.S. FDA.
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