New England Journal of Medicine Publishes 12-Week Results from Study Evaluating Atogepant for the Preventive Treatment of Migraine

- In the atogepant Phase 3 ADVANCE trial, participants experienced a significant reduction in migraine and headache days across 12 weeks of treatment¹

- 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

News provided by

AbbVie

Aug 18, 2021, 17:28 ET

NORTH CHICAGO, Ill., Aug. 18, 2021 /PRNewswire/ -- 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.

About Migraine
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.⁴It is highly prevalent, affecting more than 1 billion people worldwide, including 39 million people in the U.S. alone,⁵and is the highest cause of disability worldwide for people under 50 years of age.^6,7Due 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.

About Atogepant
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.

About AbbVie
AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health, and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, LinkedIn or Instagram.

Forward-Looking Statements
Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, failure to realize the expected benefits from AbbVie's acquisition of Allergan plc ("Allergan"), failure to promptly and effectively integrate Allergan's businesses, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable to our industry and the impact of public health outbreaks, epidemics or pandemics, such as COVID-19. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2020 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

References:
1. Ailani J, et al. Atogepant for the Preventive Treatment of Migraine. New England Journal of Medicine. 2021 August 19; Vol. 385, No. 8:695-706. DOI: 10.1056/NEJMoa2035908.
2. AbbVie. (2020, July 29). AbbVie Announces Positive Phase 3 Data for Atogepant in Migraine Prevention. https://news.abbvie.com/news/press-releases/abbvie-announces-positive-phase-3-data-for-atogepant-in-migraine-prevention.htm
3. AbbVie. (2021, March 30). U.S. FDA Accepts AbbVie's New Drug Application for Atogepant for the Preventive Treatment of Migraine. https://news.abbvie.com/news/press-releases/us-fda-accepts-abbvies-new-drug-application-for-atogepant-for-preventive-treatment-migraine.htm
4. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38:1-211.
5. Migraine Research Foundation. Migraine Facts. https://migraineresearchfoundation.org/about-migraine/migraine-facts/#:~:text=Migraine%20is%20an%20extraordinarily%20prevalent,U.S.%20and%201%20billion%20worldwide.
6. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390:1211-1259.
7. Steiner TJ, Stovner LJ, Vos T, Jensen R, Katsarava Z. Migraine is first cause of disability in under 50s: Will health politicians now take notice? J Headache Pain. 2018;19:17.

SOURCE AbbVie