Significant reductions in mean monthly migraine days compared with placebo were seen as early as weeks 1 through 4 in the clinical trial program for atogepant.
The FDA has approved atogepant (Qulipta; AbbVie) for the preventive treatment of episodic migraine in adults, marking it the first and only oral calcitonin gene-related peptide (CGRP) receptor antagonist specifically developed for the preventive treatment of migraine, according to an AbbVie press release.
The approval is based on data from a clinical program evaluating the efficacy, safety, and tolerability of atogepant in nearly 2000 patients who experienced between 4 and 14 migraine days per month. The program included the pivotal phase 3 ADVANCE study, the pivotal phase 2b/3 study, and a phase 3 long-term safety study.
Migraines are characterized by recurrent attacks that can be incapacitating, including severe, throbbing headache pain as well as compounding associated symptoms such as nausea or extreme sensitivity to light and sound. It affects more than 1 billion people globally, including 39 million people in the United States, and is the highest cause of disability worldwide for people under 50 years of age.
“Millions of people living with migraine often lose days of productivity each month because attacks can be debilitating,” said Michael Severino, MD, vice chairman and president of AbbVie, in the press release. “Qulipta can help by reducing monthly migraine days with a once-daily, oral dose that works quickly and continuously.”
In clinical trials with a 12-weeek treatment period, atogepant demonstrated statistically significant, clinically meaningful rapid and continuous reductions in mean monthly migraine days compared with placebo. Significant reductions were seen as early as weeks 1 through 4, according to the press release.
“I’m particularly encouraged by the convenience of the oral daily use of Qulipta, its rapid onset of significant efficacy, and its safety and tolerability as well as its high patient response rates,” said Peter J. Goadsby, MD, PhD, DSc, a neurologist and professor at University of California, Los Angeles, and King’s College, London, in the press release. “This is a milestone in preventive migraine treatment that I hope will help many patients for years to come.”
In the pivotal phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel group ADVANCE trial, all atogepant dose groups met the primary endpoint of change from baseline in mean monthly migraine days across the 12-week treatment period. According to the press release, patients treated with atogepant 60 mg experienced a 4.2-day reduction from a baseline of 7.8 days.
Furthermore, a key secondary endpoint in the ADVANCE trial measured the proportion of patients who achieved a 50% or greater reduction in monthly migraine days across the treatment period. The investigators found that 56%, 59%, and 61% of patients in the 10 mg, 30 mg, and 60 mg atogepant arms, respectively, achieved between 50% and 100% reduction, compared to 29% of patients in the placebo arm.
The pivotal phase 2b/3 trial also found that all active treatment arms met the primary efficacy endpoint of change in mean monthly migraine days with significantly greater reductions across the 12-week treatment period for all 3 atogepant treatment groups compared with placebo. All 3 atogepant treatment groups also met the secondary efficacy endpoint of change from baseline in mean monthly headache days, according to the press release.
All doses were well tolerated in both the ADVANCE trial and the pivotal phase 2b/3 trial. Adverse events (AEs) in both studies included nausea (5%-9% across all doses), constipation (6% across all doses), fatigue or somnolence (4%-6% across all doses), and decreased appetite (1%-2% across all doses). The AEs that most commonly led to discontinuation were constipation (0.5%), nausea (0.5%), and fatigue or somnolence (0.5%).
“This approval reflects a broader shift in the treatment and management paradigm for the migraine community,” Goadsby said in the press release. “Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients.”
FDA approves Qulipta (atogepant), the first and only oral CGRP receptor antagonist specifically developed for the preventive treatment of migraine. News release. AbbVie; September 28, 2021. Accessed September 29, 2021. https://news.abbvie.com/news/press-releases/fda-approves-qulipta-atogepant-first-and-only-oral-cgrp-receptor-antagonist-specifically-developed-for-preventive-treatment-migraine.htm