AbbVie (NYSE: ABBV) announced today that the European Commission has approved AQUIPTA® (atogepant) for migraine prevention in adults with four or more migraine days per month. AQUIPTA is now the first and only once-daily oral calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) medication approved in the European Union for the prevention of chronic and episodic migraine.
Chronic migraine is defined as 15 or more headache days per month and at least eight migraine days, whereas episodic migraine is defined as fewer than 15 headache days per month. Migraine patients may encounter frequent disabling attacks that hinder them from doing regular activities and have a negative impact on their quality of life. This debilitating disease also puts a social and financial strain on migraine patients and health-care systems. Migraine is predicted to cost the European economy €50 billion per year in missed productivity and workdays.
Atogepant Approval in US and Canada
Atogepant is approved in the United States for both chronic and episodic migraine and in Canada for episodic migraine under the brand name QULIPTA®
Basis of EU Approval of AQUIPTA(atogepant):
Data from two major Phase III studies, PROGRESS and ADVANCE, which assessed 60 mg once-daily (QD) AQUIPTA in adult patients with chronic migraine and episodic migraine, respectively, supported AQUIPTA’s approval. Across the 12-week treatment period, both studies met the primary endpoints of statistically significant reduction in mean monthly migraine days (MMDs) compared to placebo.
Furthermore, AQUIPTA 60 mg QD showed statistically significant improvements in all secondary endpoints, with a critical secondary goal evaluating the proportion of patients who obtained at least a 50% reduction in MMDs over the 12-week treatment period.
The changes from baseline in MMDs in the PROGRESS study were 6.8 days for AQUIPTA 60 mg QD and 5.1 days for placebo (p=0.0024). The study found that 40% of patients receiving AQUIPTA 60 mg QD had at least a 50% reduction in MMDs, compared to 27% of patients receiving placebo (p=0.0024).
In the ADVANCE research, the difference in MMDs from baseline was 4.1 days for AQUIPTA 60 mg QD vs 2.5 days for placebo (p0.001). The study also found that 59% of patients receiving AQUIPTA 60 mg QD had at least a 50% reduction in MMDs, compared to 29% of patients receiving placebo (p0.0001).
AQUIPTA 60 mg QD was well tolerated in both studies, with the most common side effects being constipation (8%), nausea (9%), and fatigue (5%). The most prevalent adverse medication event resulting to trial withdrawal (0.4%) was nausea.
About AQUIPTA® (atogepant):
Atogepant is an orally given CGRP receptor antagonist that has been designed exclusively for the prevention of migraine in individuals who have four or more migraine days per month. CGRP and its receptors are found in nervous system regions linked with migraine pathogenesis. CGRP levels are higher during migraine attacks, and selective CGRP receptor antagonists provide therapeutic improvement in migraine.
About the Phase 3 PROGRESS Clinical Trial:
The pivotal Phase 3 PROGRESS study evaluated the safety, tolerability, and efficacy of oral atogepant for the prophylaxis of chronic migraine compared with placebo. The study included 778 patients with a diagnosis of chronic migraine for at least one year, with greater or equal to 15 headache days and at least eight migraine days in the 28 days prior. Patients were randomized into one of three treatment groups receiving 60 mg QD of atogepant, 30 mg twice daily of atogepant, or placebo.
Primary Endpoint: reduction from baseline in mean MMDs compared to placebo for 60 mg QD across a 12-week treatment period (p=0.0024).
Secondary Endpoint: Change from baseline in mean monthly headache days (MHDs), change from baseline in mean monthly acute-medication use days, proportion of participants with at least a 50% reduction in MMDs over the 12-week treatment period, and several patient-reported outcome measures assessing functioning were key secondary endpoints.
About the Phase 3 ADVANCE Clinical Trial:
The key Phase 3 ADVANCE trial assessed the efficacy, safety, and tolerability of oral atogepant for migraine prevention in those who have 4 to 14 migraine days per month. A total of 910 patients were randomly assigned to one of four therapy groups: atogepant QD (10 mg, 30 mg, or 60 mg) or placebo.
Primary Endpoint: The primary outcome was change from baseline in mean MMDs for 60 mg QD compared to placebo throughout a 12-week treatment period (p0.001). The study found that atogepant 60 mg QD therapy resulted in statistically significant improvements in all main and secondary outcomes.
Secondary Endpoint: Change from baseline in MHDs, mean monthly acute-medication usage days, proportion of patients achieving at least a 50% reduction from baseline in MMDs across the 12-week treatment period, and numerous patient-reported outcome measures assessing functioning were key secondary endpoint.
Expert Opinion on EU Approval of AQUIPTA(atogepant):
“The European Commission approval of AQUIPTA is a significant milestone for people suffering from four or more migraine days per month as it provides a once-daily treatment option that can reduce the number of migraine days and the associated pain they experience,” said Roopal Thakkar, SVP, Development and Regulatory Affairs, Chief Medical Officer, AbbVie. “With this approval, AbbVie can help meet additional migraine patient needs through our enhanced portfolio of treatment options across migraine frequencies, including episodic and chronic migraine.”
“Migraine is a neurological disease that causes recurrent pain and other migraine-associated symptoms, with attacks that can last several hours to days, leading to missed life opportunities,” said Prof. Patricia Pozo-Rosich, MD, PhD, Head of Neurology Section, Vall d’Hebron Hospital and Institute of Research, Spain. “The pivotal Phase 3 studies demonstrated AQUIPTA provides significant and sustained reduction of mean monthly migraine days. This allows people to experience relief with a simple to take once-daily tablet, including those who have had an insufficient response to prior preventative migraine treatments.”
