U.S. FDA Accepts AbbVie's New Drug Application for Atogepant for the Preventive Treatment of Migraine
- Category: Small Molecules
- Published on Tuesday, 30 March 2021 16:23
- Hits: 611
- If approved, atogepant will be the first and only oral CGRP receptor antagonist specifically developed for the preventive treatment of migraine
- In the Phase 3 ADVANCE trial for the preventive treatment of migraine in adults with 4-14 migraine days, all active treatment arms of atogepant met their primary endpoint, and the 30 and 60 mg doses met all six secondary endpoints with statistical significance
- Migraine is a debilitating neurological disease affecting 39 million people in the U.S.
- The atogepant application demonstrates AbbVie's longstanding commitment to providing multiple migraine treatment options, including BOTOX® (onabotulinumtoxinA), a preventive treatment for those with chronic migraine, and UBRELVY® (ubrogepant), an acute treatment for adults with migraine
NORTH CHICAGO, IL, USA I March 30, 2021 I AbbVie (NYSE: ABBV) today announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for atogepant, an investigational orally administered calcitonin gene-related peptide (CGRP) receptor antagonist (gepant), for the preventive treatment of migraine in adults who meet criteria for episodic migraine. AbbVie anticipates a regulatory decision in late Q3 2021.
Migraine is a complex, chronic disease with attacks that are often incapacitating and can include headache pain as well as neurologic and autonomic symptoms.3 Migraine symptoms and severity range widely among individuals.
The NDA is supported by data from a robust clinical program evaluating the efficacy, safety and tolerability of orally administered atogepant in nearly 2,500 patients who experience 4-14 migraine days per month including but not limited to the pivotal Phase 3 ADVANCE study, the pivotal Phase 2b/3 study, and the Phase 3 long-term safety study.
"With the integration of Allergan, AbbVie is now a committed leader in migraine with an almost 25-year history in migraine research. We look forward to potentially adding a new treatment option to our portfolio that will help more people with migraine," said Michael Gold, MD, vice president, neuroscience development, AbbVie. "We believe atogepant is an advancement with the potential to offer meaningful benefits as a safe, effective oral preventive treatment option. Despite the availability of other migraine treatment options, the medical community and people living with migraine recognize the unmet need of those who face the unpredictable and debilitating realities of this disease."
In the Phase 3 ADVANCE study, all active treatment arms of atogepant met their primary endpoint of a statistically significant reduction in mean monthly migraine days over a 12-week treatment period. Also, the 30 and 60 mg doses met all six secondary endpoints with statistical significance. This study followed positive results from the Phase 2b/3 study that met the same primary endpoint across all doses and dosing regimens. The Phase 3 long-term safety study evaluated safety and tolerability of 60 mg oral atogepant administered daily over 52 weeks. The Phase 3 long-term safety study will be presented at the American Academy of Neurology 2021 Virtual Annual Meeting. Results from the Phase 2b/3 study and the Phase 3 ADVANCE study were previously announced.1,4
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 primary endpoint was change from baseline in mean monthly migraine days across the 12-week treatment period. All atogepant dose groups met the primary endpoint and demonstrated statistically significant reductions in mean monthly migraine days compared to placebo. Patients treated in the 10 mg, 30 mg, and 60 mg atogepant arms experienced a decrease of 3.69, 3.86, and 4.2 days, respectively, compared to patients in the placebo arm, who experienced a decrease of 2.48 days (all dose groups vs. placebo, p=<.0001).
A key secondary endpoint measured the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days 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 at least a 50% reduction, compared to 29.0% of patients in the placebo arm (all dose groups vs. placebo, p=<.0001).
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 vs. 0.5% for placebo), nausea (4.4-6.1% across all doses vs. 1.8% for placebo), and upper respiratory tract infection (3.9-5.7% across all doses vs. 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.
The study results were announced in a July 2020 press release and presented at the 2020 Virtual Migraine Trust International Symposium.
About the Phase 2b/3 CGP-MD-01 Study
The pivotal Phase 2b/3 clinical trial evaluating the efficacy, safety and tolerability of orally administered atogepant demonstrated that all active treatment arms met the primary endpoint with a statistically significant reduction from baseline in mean monthly migraine days compared with placebo across the 12-week treatment period in those with 4 to 14 migraine days per month. The results were announced in a June 2018 press release and were also presented at the 2019 American Headache Society Annual Meeting.
About the Phase 3 Long-Term Safety Study
The Phase 3, multicenter, randomized, open-label study evaluated the long-term safety and tolerability of 60 mg oral atogepant administered daily over 52 weeks for the preventive treatment of migraine in adults with 4-14 migraine days per month. Further details on the study will be presented at the American Academy of Neurology 2021 Virtual Annual Meeting.
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.2 It is highly prevalent, affecting more than 1 billion people worldwide, including 39 million people in the U.S. alone,2 and is the highest cause of disability worldwide for people under 50 years of age.5,6 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.
About AbbVie Leadership in Migraine
AbbVie, a leader in the migraine space, markets BOTOX® (onabotulinumtoxinA), the first FDA-approved, preventive treatment for adults with chronic migraine and UBRELVY® (ubrogepant), the first FDA-approved oral calcitonin gene-related peptide (CGRP) receptor antagonist (gepant), which is indicated for the acute treatment of migraine with or without aura in adults.
BOTOX® is a prescription medicine that is injected into muscles and used:
- To prevent headaches in adults with Chronic Migraine who have 15 or more days each month with headache lasting 4 or more hours each day in people 18 years or older
It is not known whether BOTOX® is safe and effective to prevent headaches in patients with migraine who have 14 or fewer headache days each month (episodic migraine).
UBRELVY (ubrogepant) is indicated for the acute treatment of migraine with or without aura in adults. UBRELVY is not indicated for the preventive treatment of migraine.
IMPORTANT SAFETY INFORMATION
Contraindication: Concomitant use of strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin).
Adverse Reactions: The most common adverse reactions were nausea (4%) and somnolence (3%).
Please see UBRELVY full Prescribing Information.
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.
1. 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
2. Migraine Research Foundation. Migraine Facts. https://migraineresearchfoundation.org/about-migraine/migraine-facts/#:~:text=Migraine%20is%20an%20extraordinarily%20prevalent,U.S.%20and%201%20billion%20worldwide.
3. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38:1-211.
4. Allergan, an AbbVie Company. (2018, June 11). Allergan's Oral CGRP Receptor Antagonist Atogepant Demonstrates Robust Efficacy and Safety in Episodic Migraine Prevention in a Phase 2b/3 Clinical Trial. https://www.prnewswire.com/news-releases/allergans-oral-cgrp-receptor-antagonist-atogepant-demonstrates-robust-efficacy-and-safety-in-episodic-migraine-prevention-in-a-phase-2b3-clinical-trial-300663770.html
5. 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.
6. 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.