AbbVie Announces Positive Phase 3 Data for Atogepant in Migraine Prevention
- Category: Small Molecules
- Published on Wednesday, 29 July 2020 19:41
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- Phase 3 ADVANCE trial evaluating atogepant meets primary endpoint of statistically significant reduction from baseline in mean monthly migraine days, compared to placebo, for all doses evaluated across a 12-week treatment period
- Trial also demonstrates statistically significant improvements in all six secondary endpoints in the 30 mg and 60 mg once-daily treatment arms
- Data from this trial and previous Phase 2/3 trial will be the basis for regulatory submissions in the U.S. and other countries
- These results support AbbVie's commitment to providing multiple treatment options, including BOTOX® (onabotulinumtoxinA) for the prevention of chronic migraine and UBRELVY™ (ubrogepant), to treat migraine
NORTH CHICAGO, IL, USA I July 29, 2020 I AbbVie (NYSE: ABBV) today announced that the Phase 3 ADVANCE trial evaluating the investigational medicine atogepant, an orally administered calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) met its primary endpoint of statistically significantly greater reduction in mean monthly migraine days, compared to placebo, for all doses across the 12-week treatment period. With these results, combined with the prior positive Phase 2/3 trial, AbbVie plans to move forward with regulatory submissions in the United States and other countries. Full data results will be presented at an upcoming medical congress and/or published in a peer-reviewed journal.
"Migraine attacks can be debilitating, but migraine is a treatable disease, and people living with it are not alone in their battle to control it," said Thomas J. Hudson, M.D., senior vice president of R&D and chief scientific officer, AbbVie. "With the results from these trials, we aim to provide a safe and effective preventive treatment that offers patients and healthcare providers a simple, once daily oral treatment that works specifically by blocking CGRP receptors and preventing migraine."
About the Pivotal ADVANCE Trial
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 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 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 significantly greater decreases in mean monthly migraine days compared to placebo. Patients treated in the 10 mg/30 mg/60 mg atogepant arms experienced a decrease of 3.69/3.86/4.2 days, respectively, all 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%/60.8% of patients in the 10 mg/30 mg/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).
Additional secondary endpoints measured across the 12-week treatment period included change from baseline in mean monthly headache days, 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), and change from baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Role Function-Restrictive domain score at week 12. The trial demonstrated that treatment with 30 mg and 60 mg doses resulted in statistically significant improvements in all secondary endpoints, while treatment with the 10 mg dose resulted in statistically significant improvements in four out of the six secondary endpoints.
No new safety risks were observed compared to the safety profile observed in the previous trial evaluating atogepant. Serious adverse events occurred in 0.9% of patients treated in the atogepant 10 mg arm compared to 0.9% of patients in the placebo arm. No patients in the atogepant 30 mg or 60 mg treatment arms experienced a serious adverse event. 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. There were no hepatic safety issues identified in this trial.
About the Phase 2/3 CGP-MD-01 Study
The Phase 2/3 clinical trial evaluating the efficacy, safety, and tolerability of orally administered atogepant, demonstrated that all active treatment arms of atogepant met the primary endpoint with a statistically significant reduction from baseline in mean monthly migraine days compared with placebo across the 12 week-week treatment period (10 mg QD vs placebo, p=0.0236; 30 mg QD vs placebo, p=0.0390; 60 mg QD vs placebo, p=0.0390; 30 mg BID vs placebo; p=0.0034, 60 mg BID vs placebo, p=0.0031).* The results were announced in a press release issued in June 2018.
Migraine is a complex, chronic disease with episodic attacks that are often incapacitating and characterized by headache pain as well as neurologic and autonomic symptoms. It is highly prevalent, affecting more than one billion people worldwide, and is the highest cause of disability worldwide for people under 50 years of age., Due to the unpredictability and fluctuation of attack frequency and severity, migraine has substantial impact on many aspects of an individual's life both during and between attacks. Daily activities, work, school, and personal relationships are negatively affected, leading to a significant burden on the person with migraine, their family, and friends, and often extending to employers and healthcare systems.
Atogepant is an 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 or 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.
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, Instagram, YouTube and LinkedIn.
* The reported p-values are adjusted for multiple comparisons by controlling the overall type I error rate of the study at 5%, 2-sided.
1 Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38:1-211.
2 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.
3 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.