Results from the open-label, 156-week extension phase 3 trial (NCT04686136) that evaluated the long-term safety and tolerability of atogepant (Qulipta; AbbVie) for the prevention of migraines in patients with chronic or episodic migraine were announced. The findings demonstrated that atogepant’s safety profile was consistent with previous data and no new safety signals were detected. The findings will be presented at the American Academy of Neurology Annual Meeting from April 13, 2024, to April 18, 2024, in Denver, Colorado.
About the Trials
1. Extension Trial (Study 3101-312-002)
- Trial Name: A Long-Term Safety and Tolerability Extension Study Evaluating Atogepant for the Prevention of Chronic or Episodic Migraine
- ClinicalTrials.gov ID: NCT04686136
- Sponsor: Allergan
- Completion Date (Estimated): September 13, 2024
2. PROGRESS Study
- Trial Name: Efficacy, Safety, and Tolerability of Atogepant for the Prevention of Chronic Migraine
- ClinicalTrials.gov ID: Allergan
- Sponsor: NCT03855137
- Completion Date: January 20, 2022
3. ELEVATE Study
- Trial Name: Atogepant for Prophylaxis of Migraine in Participants Who Failed Previous Oral Prophylactic Treatments (ELEVATE)
- ClinicalTrials.gov ID: NCT04740827
- Sponsor: Allergan
- Completion Date: August 4, 2022
Atogepant is an oral, CGRP receptor agonist that is designed specifically to be a preventative migraine treatment in adult patients. CGRP and its receptors are expressed in regions of the nervous system associated with migraine pathophysiology, and previous research indicated that CGRP levels elevated during migraines which suggests that selective CGRP receptor agonists may provide clinical benefit during attacks.
"Migraine is a debilitating neurological disease that can have a significant impact on day-to-day life," said lead study author Sait Ashina, MD, assistant professor of neurology and anesthesia at Harvard Medical School, director of the Comprehensive Headache Center at Beth Israel Deaconess Medical Center in Boston, in a press release.
The extension phase 3 trial, Study 3101-312-002, is an ongoing study evaluating the long-term safety and tolerability of oral atogepant for the prevention of migraine in 595 participants with episodic or chronic migraine disorders. The study’s primary objective is to evaluate the safety and tolerability in all participants who received at least 1 dose of atogepant. Pre-specified efficacy end points included change from baseline in monthly migraine days (MMDs), monthly headache days (MHDs), monthly acute medication use days, and the proportion of patients with at least 50% improvement in monthly migraine days. Enrolled participants were also involved in 2 prior global, randomized, double-blind, placebo-controlled phase 3 trials, PROGRESS (NCT03855137) and ELEVATE (NCT04740827).
Findings of the extension trial’s interim analysis demonstrated that monthly migraine days were improved by an average of 8.5 days at weeks 13 through 16 and was consistent through 48 weeks in patients who received atogepant. The researchers noted similar improvements were observed for both monthly headache days and monthly acute medication days. Further, approximately 70% of participants had achieved at least a 50% reduction in monthly migraine days that was consistent through 48 weeks, and overall safety results were consistent with the previously known safety profile of a 60 mg-dose of atogepant.
"As the first report of 1-year atogepant data in patients with chronic migraine, this builds on the long-term observed safety and efficacy in the episodic migraine population and demonstrates atogepant's ability to reduce migraine days and acute medication use across the spectrum of the disease,” said Ashina in the press release.
The PROGRESS study assessed the efficacy, safety, and tolerability of atogepant for the preventative treatment of chronic migraine. Adult patients who have at least a 1-year history with chronic migraine were randomly assigned to orally receive either 30 mg twice-daily of atogepant (which is not an FDA-approved dose), 60 mg once-daily of atogepant, or placebo. The primary end point for this study was change from baseline in MMDs across the 12-week treatment period, and key secondary end points included proportion of participants with at least a 50% reduction in MMDs, change from baseline in mean MHDs, and change from baseline in mean monthly acute medication use days across the 12-week treatment period.
The ELEVATE study assessed the safety, tolerability, and efficacy of 60 mg once-daily of oral atogepant and compared it with placebo. Patients with episodic migraine who failed 2 or 4 classes of oral preventative treatments were enrolled in the study. The primary end point was the same as the PROGRESS trial, and secondary end points included achievement of more than 50% reduction in MMDs, change from baseline in mean MHDs, and change from baseline in acute medication use days across 12 weeks.
In the extension trial, the most common treatment-emergent adverse events (TEAEs) were COVID-19 infection (28.7%), nasopharyngitis (10.9%), and constipation (8.2%). Other potential TEAEs that were not reported by trial participants are nausea and fatigue.
"We understand that migraine is a complex disease and AbbVie is steadfast in our commitment to alleviating the considerable burden facing patients [with migraine]," said Dawn Carlson, vice president, neuroscience development, AbbVie. "Patients should accept nothing less than migraine freedom, and the long-term safety and efficacy shown in this interim analysis marks another step toward that goal."
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