Atogepant emerges as potential migraine prophylaxis
Atogepant, a novel oral calcitonin gene-related peptide (CGRP) receptor antagonist, has shown potential in prevention of migraine at a range of doses, according to a presentation at the recent American Headache Society conference (AHS 2019).
Participants in this multicentre, double-blind, placebo-controlled phase IIb/III trial were 834 individuals (mean age 40.1 years, 86.5 percent female, 76.1 percent Caucasian) with a history of migraine, with or without aura, who had experienced 4–14 migraine days (mean 7.67 days) in the 28-day baseline period. A majority of the patients (71.9 percent) had not previously received prophylaxis for migraine. They were randomized to one of five doses of atogepant (10 mg QD [n=92], 30 mg QD [n=182], 30 mg BID [n=79], 60 mg QD [n=177], or 60 mg BID [n=87]), with each dose compared with placebo (n=178) for 12 weeks.
Over the 12-week treatment period, patients on all doses of atogepant had significantly fewer monthly migraine days compared with those on placebo. [AHS 2019, abstract IOR01]
Compared with placebo-treated patients who experienced a mean 2.85-day reduction in monthly migraine days, patients treated with atogepant 10 mg, 30 mg, and 60 mg QD had a mean 4-day (p=0.0236), 3.76-day (p=0.0390), and 3.55-day (p=0.0390) reduction in monthly migraine days.
Patients treated with atogepant at doses of 30 mg or 60 mg BID also had significant reductions in monthly migraine days compared with those who received placebo (mean, -4.23; p=0.0034 and -4.14; p=0.0031, respectively).
More than half of the 825 patients in the safety analysis population reported adverse events (AEs; 58.2 percent [n=480]), with 20.6 percent (n=170) deemed treatment-related AEs. Seven patients experienced serious AEs, though none of these AEs were considered treatment-related. The 10 cases of treatment-emergent elevations in aspartate aminotransferase or alanine aminotransferase of >3 times the upper limit of normal occurred at a comparable rate between groups.
“These exciting results demonstrate the potential for atogepant for a broad spectrum of migraine patients,” said study author Professor Peter Goadsby from Kings College, London, UK, when the results were first released.
“Broadly, [atogepant] will likely be useful in patients who have not responded to, or have been intolerant of, or with contraindications to current preventive therapies,” he said, describing the patient population best suited for treatment with atogepant.
“The efficacy and safety across doses and dose regimens show promise in a patient population with high unmet treatment needs. Results from this atogepant trial provide continued evidence for the clinical potential of oral CGRP antagonists and the substantial value of progressing research and developing new treatments for migraine patients,” he said.
“[The results also show that] small molecule CGRP receptor antagonists have potential as migraine preventives, in addition to a role as acute treatments,” said Goadsby. “[However, as] this was a phase II/III trial, I think the phase III programme needs to be done to be clear about this [result].”