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Atogepant is an investigational (not FDA-approved) drug for migraine prevention that targets calcitonin gene-related peptide (CGRP). Now, researchers have conducted a dose-ranging, manufacturer-sponsored phase IIb/III study of an oral formulation of atogepant. They randomized 834 adults with episodic migraine (4 to 14 days per month; mean, 7.7 days) of ≥1 year duration to placebo or atogepant in 10-mg, 30-mg, 60-mg once-daily doses or 30-mg or 60-mg twice-daily doses.
After 3 months of daily use, all atogepant groups had significantly greater reductions in mean number of migraine days per month than the placebo group. Reductions from baseline with atogepant ranged from −3.6 to −4.2 days per month vs. −2.9 days per month with placebo. The most common adverse effect was nausea, which was dose dependent (5%–12%). Liver enzymes elevation more than 3 times the upper limit was seen in 1% to 2% of atogepant recipients and in 1% of placebo recipients.
Goadsby PJ et al. Safety, tolerability, and efficacy of orally administered atogepant for the prevention of episodic migraine in adults: A double-blind, randomised phase 2b/3 trial. Lancet Neurol 2020 Sep; 19:727. (https://doi.org/10.1016/S1474-4422(20)30234-9)
Comment
Since the approval of first anti-CGRP class of medicines (erenumab) in May 2018, the FDA has approved 5 more drugs in the same class as of October 2020. If approved, atogepant would be the only oral formulation in the preventative category of anti-CGRP molecules. The authors propose that this oral preventative formulation may have an advantage for patients who are planning to become pregnant because its half-life is only 10 hours and it can be discontinued faster than other subcutaneous and intravenous anti-CGRP preventatives (21–48 days). In terms of primary and secondary outcomes, atogepant did not outperform its competitors in the same class. The future potential use could be in patients who had injection related side effects to anti-CGRP injectables. A trial for chronic migraine is underway. The real test will be its safety with long-term use. In the past, a trial of another oral preventative, telcagepant, was halted due to liver toxicity.