AbbVie announced positive results from its phase 3 ELEVATE trial investigating atogepant (Qulipta) for preventive treatment of episodic migraine in adult patients who had previously failed multiple oral preventive medications. The global, randomized, double-blind, placebo-controlled study demonstrated statistically significant efficacy in a challenging patient population with treatment-resistant migraine.
Trial Results Show Superior Efficacy
The ELEVATE trial enrolled 309 participants with episodic migraine who had previously failed 2 to 4 classes of oral preventive medications due to concerns with efficacy or tolerability. Among the study population, 56% had previously failed two classes of oral migraine preventive medications and 44% had previously failed three or more classes.
Across the 12-week treatment period, patients receiving atogepant 60 mg once daily experienced a decrease of 4.20 days in their mean monthly migraine days (MMDs), which was statistically significantly greater than the 1.85 day reduction observed in the placebo arm (P < .0001).
The trial met all primary and secondary endpoints, with secondary measures including achievement of more than 50% reduction in MMDs, change from baseline in MMDs, and change from baseline in acute medication use days, all assessed across 12 weeks.
Safety Profile Remains Consistent
Atogepant 60 mg once daily was well tolerated compared with placebo, with safety results consistent with the known safety profile of the treatment. The most commonly reported treatment-emergent adverse events occurring in at least 5% of each treatment arm were constipation (10.3% vs 2.5% for placebo), COVID-19 (8.3% vs 9.6%), nausea (7.1% vs 3.2%), and nasopharyngitis (5.1% vs 7.6%).
European Regulatory Progress
The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending approval of atogepant for the prophylaxis of migraine in adults who have four or more migraine days per month. If approved, AbbVie would be the only company to offer a once-daily oral calcitonin gene-related peptide (CGRP) receptor antagonist treatment spanning both episodic and chronic migraine in the European Union.
The positive CHMP opinion is supported by data from two pivotal phase 3 studies, PROGRESS and ADVANCE, which evaluated 60 mg once daily atogepant in adult patients with chronic and episodic migraine, respectively. In the PROGRESS study, changes from baseline in MMDs were -6.8 days for atogepant 60 mg once daily and -5.1 days for placebo. In the ADVANCE study, changes from baseline in MMDs were -4.1 days for atogepant 60 mg once daily and -2.5 days for placebo.
Clinical Significance for Migraine Management
"For those living with migraine, the path towards effective treatment can be a long and complex journey," said Patricia Pozo-Rosich, MD, PhD, professor of neurology and head of the Neurology Section at Vall d'Hebron Hospital and Institute of Research in Spain. "The ELEVATE trial demonstrates atogepant as a once-daily oral treatment that can significantly reduce monthly migraine days across a lifelong disorder, allowing people to experience relief in their daily lives, including those who have previously been failed by other preventive migraine treatments."
Migraine affects an estimated 1 billion people worldwide and is among the highest causes of disability for people under 50 years of age. In Europe, migraine is estimated to cost the economy €50 billion ($54.4 billion) annually due to reduced productivity and workdays lost.
Mechanism of Action and Development
Atogepant is an oral calcitonin gene-related peptide receptor antagonist specifically developed for the preventive treatment of migraine. CGRP and its receptors are expressed in regions of the nervous system associated with migraine pathophysiology, and studies have shown that CGRP levels are elevated during migraine attacks.
The drug was originally approved in September 2021 based on results from its full clinical development program, including the ADVANCE study. In April 2023, the FDA expanded the indication to include prevention of chronic migraine in adults, adding to its existing indication for episodic migraine.
"We understand that people living with migraine endure a chronic neurological disease and we are dedicated to providing them the best chance to live a life with less frequent migraines," said Dawn Carlson, vice president of neuroscience development at AbbVie. "The data presented at AAN underscores the important role of atogepant, not only as a treatment option for people living with episodic migraine but also for those whose previous treatments failed to help reduce the impact of migraine on their lives."
