A potential prophylactic treatment, atogepant, was developed by Allergan and is now being progressed by AbbVie (having acquired Allergan in 2019).
It is an oral calcitonin gene-related peptide (CGRP) receptor antagonist; CGRP levels are elevated during migraine attacks, so blocking this may have clinical benefits in migraine sufferers.
A double-blind Phase IIb/III was done in 825 adults with a history of migraine and 4–14 migraine days a month.1 Subjects were randomised to receive 10, 30 or 60 mg once a day, 30 or 60 mg twice a day or a placebo for 12 weeks.
All five groups given atogepant had a significant change from baseline in mean monthly migraine days compared with the placebo: the reductions were 4.0, 3.8, 3.6, 4.2 and 4.1 days, compared with the placebo, for which the reduction was 2.9 days. The most common adverse events were nausea and fatigue.
In a double-blind Phase III trial, 910 adult patients with 4–14 migraine days a month (with a mean of 7.5–7.9 across the groups) were enrolled and randomly assigned to receive 10, 30 or 60 mg of atogepant or a placebo once a day for 12 weeks.2
The reductions in number of migraine days a month were, respectively, 3.7, 3.9, 4.2 and 2.5. Improvements were also seen in various secondary endpoints, including number of headache days per month and quality of life.
The most common adverse events were constipation and nausea. A further analysis of the results showed that treatment benefits were seen as early as the day after dosing started and efficacy was sustained through the trial.3
It has also been assessed in 32 patients with hepatic impairment.4 Subjects with severe, moderate, mild or no impairment (eight of each) were matched with participants with normal hepatic function from an open label Phase I trial. It was absorbed rapidly and had an apparent terminal elimination half-life of 11 hours.
Systemic exposure to the drug was 15–38% higher in those with hepatic impairment compared with those with none, but the researchers felt this should not be clinically relevant given atogepant’s safety profile.
References
- P.J. Goadsby, et al., Lancet Neurol. 19, 727 (2020).
- J. Ailani, et al., N. Engl. J. Med. 385, 695 (2021).
- T.J. Schwedt, et al., Cephalalgia 42, 3 (2022).
- R. Boinpally, et al., Clin. Pharmacol. Drug Dev. 10, 726 (2022).
