AbbVie Secures Positive CHMP Opinion for Atogepant for the Preventive Treatment of Adults with Migraine

• If approved by the European Commission (EC), atogepant will be the first and only once daily oral calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) in the European Union (EU) for the prophylaxis of migraine in adults who have four or more migraine days per month
• The positive CHMP opinion is based on results from two pivotal Phase 3 studies evaluating atogepant for the prophylaxis of migraine in adults with episodic or chronic migraine

NORTH CHICAGO, Ill., June 23, 2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the approval of atogepant for the prophylaxis of migraine in adults who have four or more migraine days per month. If approved, AbbVie will be the only company to offer a once daily oral calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) treatment spanning both episodic and chronic migraine in the European Union (EU).

Chronic migraine (CM) is characterized by 15 or more headache days a month and at least eight migraine days, while episodic migraine (EM) refers to people with migraine who have less than 15 headache days per month.¹ In Europe, migraine is estimated to cost the economy €50 billion annually due to reduced productivity and workdays lost.²

"Migraine is a complex neurological disease and one of the leading causes of disability worldwide, which is why we continue to advance our science to provide effective treatment options for people living with this debilitating condition," said Dawn Carlson, vice president, neuroscience development, AbbVie. "The recent positive CHMP opinion of atogepant brings us closer to providing a new therapy option to those living with migraine in the European Union."

The positive CHMP opinion for atogepant is supported by data from two pivotal Phase 3 studies, PROGRESS and ADVANCE, which evaluated 60 mg once daily (QD) atogepant in adult patients with chronic and episodic migraine, respectively. Both studies met their primary endpoint of a statistically significant reduction in mean monthly migraine days (MMDs), compared to placebo across the 12-week treatment period. Additionally, statistically significant improvements were seen in all secondary endpoints with atogepant 60 mg QD.^3,4

In the PROGRESS study, the changes from baseline in MMDs were −6.8 days for atogepant 60 mg QD and -5.1 days for placebo (p=0.0024).³ In the ADVANCE study, the changes from baseline in MMDs were −4.1 days for atogepant 60 mg QD and −2.5 days for placebo (p=<0.001).⁴ In both studies, atogepant 60 mg QD was well tolerated and the most common adverse events were constipation, nausea, and fatigue. The adverse drug reaction most commonly leading to study discontinuation was nausea (0.4%).^3,4

"Far too many people around the world are impacted by migraine, and the path to treatment can be long and complex," said Prof. Patricia Pozo-Rosich, MD, PhD, Head of Neurology Section, Vall d'Hebron Hospital and Institute of Research, Spain. "The approval of atogepant would represent a meaningful advancement for the migraine community in the European Union, providing adults with four or more migraine days per month a new prophylactic treatment option that offers the possibility of sustained migraine prevention."

Migraine is highly prevalent, affecting 1 billion people worldwide⁵, including an estimated 41 million people in Europe.⁶ Individuals with migraine experience frequent disabling migraine attacks, preventing them from performing daily activities and significantly affecting their quality of life.⁷ This debilitating disease imposes both a social and financial burden for people living with migraine and healthcare systems.⁸

About Atogepant
Atogepant is an orally administered, CGRP receptor antagonist specifically developed for the preventive treatment of migraine in adults who have four or more migraine days per month. 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.

About the Phase 3 PROGRESS Clinical Trial³
The pivotal Phase 3 PROGRESS study evaluated the safety, tolerability, and efficacy of oral atogepant for the prophylaxis of chronic migraine compared with placebo. The study included 778 patients with a diagnosis of chronic migraine for at least one year, and greater or equal to 15 headache days with at least eight migraine days in the 28 days prior. Patients were randomized into one of three treatment groups receiving 60 mg QD of atogepant, 30 mg twice daily of atogepant, or placebo. The primary endpoint measured the reduction from baseline in MMDs compared to placebo for 60 mg QD across a 12-week treatment period (p=0.0024). The overall safety profile observed in the Phase 3 PROGRESS study was consistent with safety findings observed in previous studies. The most common adverse events reported with a frequency greater than or equal to 5% in the atogepant 60 mg QD arm were constipation (10.0% vs. 3.1% for placebo) and nausea (9.6% vs. 3.5% for placebo). Most of the events of constipation and nausea were mild or moderate in severity and did not lead to study discontinuation.

Additional key secondary endpoints included change from baseline in mean monthly headache days (MHDs), change from baseline in mean monthly acute-medication use, proportion of participants with at least a 50% reduction in MMDs across the 12-week treatment period and change from baseline in Migraine-Specific Quality-of-Life Questionnaire Version 2.1 (MSQ v2.1) Role Function-Restrictive (RFR) domain score at week 12. MSQ v2.1 is designed to measure health-related quality of life impairments attributed to migraine.

For a full listing of secondary endpoints across all regions, please go to www.clinicaltrials.gov (NCT03855137).

About the Phase 3 ADVANCE Clinical Trial⁴
The pivotal Phase 3 ADVANCE study evaluated the efficacy, safety, and tolerability of oral atogepant for the prevention 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, or 60 mg of atogepant QD, or placebo. The primary endpoint was change from baseline in MMDs compared to placebo for 60 mg QD across a 12-week treatment period (p<0.001). The study demonstrated that treatment with atogepant 60 mg QD resulted in statistically significant improvements in all the primary and secondary endpoints. The most common adverse events reported with a frequency greater than or equal to 5% in the atogepant 60 mg QD arm were constipation (6.9% vs. 0.5% for placebo), nausea (6.1% vs. 1.8% for placebo), and upper respiratory tract infection (3.9% vs. 4.5% for placebo). Most of the events of constipation and nausea were mild or moderate in severity and did not lead to study discontinuation.

Additional key secondary endpoints included change from baseline in MHDs, mean monthly acute-medication use days, and mean monthly performance of daily activities and physical impairment domain scores of the Activity Impairment in Migraine-Diary (AIM-D) across the 12-week treatment period, and change from baseline in the MSQ v2.1 RFR domain score at week 12. The AIM-D is a questionnaire designed to evaluate difficulty with performance of daily activities and physical impairment due to migraine.

For a full listing of secondary endpoints across all regions, please go to www.clinicaltrials.gov (NCT03777059).

About AbbVie in Neuroscience
At AbbVie, our commitment to preserving personhood of people around the world living with neurological and psychiatric disorders is unwavering. With more than three decades of experience in neuroscience, we are providing meaningful treatment options today and advancing innovation for the future. AbbVie's Neuroscience portfolio consists of approved treatments in neurological conditions, including migraine, movement disorders, and psychiatric disorders, along with a robust pipeline of transformative therapies. We have made a strong investment in research and are committed to building a deeper understanding of neurological and psychiatric disorders. Every challenge makes us more determined and drives us to discover and deliver advancements for those impacted by these conditions, their care partners, and clinicians. For more information, visit www.abbvie.com.

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, Instagram, YouTube, and LinkedIn.

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 and uses of future or conditional verbs, 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 expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. 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 2022 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, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

References 

¹ Curr Pain Headache Rep. 2012; 16(1): 86–92.
² Rethinking Migraine in times of COVID-19. European Brain Council. 2023. https://www.braincouncil.eu/projects/rethinking-migraine/. Accessed June 2023.
³ AbbVie. Data on File: ABVRRTI76375
⁴ Ailani J, et al. NEJM. Atogepant for the Preventive Treatment of Migraine. 2021; 385:695-706. DOI: 10.1056/NEJMoa2035908.
⁵ Global Burden of Disease Study. 2016. Lancet Neurology 2018;17:954–76. 
⁶ Rethinking Migraine in times of COVID-19. European Brain Council. 2023. Available at: https://www.braincouncil.eu/projects/rethinking-migraine/. Accessed May 31, 2023.
⁷ Lantéri-Minet M, Duru G, Mudge M, Cottrell S. Quality of life impairment, disability and economic burden associated with chronic daily headache, focusing on chronic migraine with or without medication overuse: a systematic review. Cephalalgia. 2011;31:837-850.
⁸ Messali A, Sanderson JC, Blumenfeld AM, et al. Direct and indirect costs of chronic and episodic migraine in the United States: a web-based survey. Headache. 2016;56:306-322.

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