Treatment with Atogepant, an oral, low molecular weight calcitonin gene-related peptide (CGRP) receptor antagonist, is safe and effective for migraine prophylaxis, according to the full results of the ADVANCE phase 3 study published in the New England Journal of Medicine has been published.
Previous studies have shown elevated blood levels of CGRP during a migraine attack, suggesting that the molecule plays an important role in the pathophysiology of migraines. Several CGRP-based treatments are available for migraine prophylaxis, but they are all administered by injection, while oral CGRP receptor antagonists are approved for acute migraines, but not as a prophylactic treatment option.
An earlier phase 2-3 dose-finding study confirmed the effectiveness of atogepant in reducing migraine days. The aim of the current Phase 3 study was to determine the safety and efficacy of atogepant, administered orally at a dose of 10 mg, 30 mg or 60 mg once daily, compared to placebo for migraine prophylaxis in patients with episodic migraines determine.
The change in the mean number of migraine days per month over the study period was the primary efficacy endpoint.
The multicentre, double-blind, randomized, placebo-controlled, parallel group study enrolled 902 patients (safety population that included all patients who received at least 1 dose of atogepant or placebo; mean age 41.6 years; 88.8% women) with at least 1 year of episodic migraine with or without History of aura. Participants were randomized to receive a once daily dose of atogepant (10 mg, 30 mg, or 60 mg) or placebo for 12 weeks.
At week 12, the mean reduction from baseline in the mean number of migraine days per month was 3.7 days with 10 mg atogepant, 3.9 days with 30 mg atogepant, 4.2 days with 60 mg atogepant and 2.5 days with placebo . The differences between each active dose and placebo were statistically significant (P <0.001).
The average number of headache days per month over the 12-week treatment period also decreased: 3.9 days with 10 mg Atogepant, 4.0 days with 30 mg Atogepant, 4.2 days with 60 mg Atogepant and 2.5 days with placebo . The differences between each active dose and placebo were statistically significant (P <0.001).
In 55.6% of the participants in the 10 mg atogepant group, 58.7% of the participants in the 30 mg atogepant group and 60.8% of the participants in the 60 mg atogepant group and 29 , 0% of those in the placebo group (p <0.001 for all comparisons with placebo).
The most common side effects in patients treated with Atogepant were constipation (6.9% to 7.7% over the Atogepant doses), nausea (4.4% to 6.1%), and upper respiratory tract infections (1.4% up to 3.9%). The incidence of discontinuation due to adverse events was similar across the study groups.
The study had several limitations. These included the short duration and exclusion of patients with 15 or more headache days per month, the exclusion of patients treated with triptans or ergot for 10 or more days per month, and the exclusion of patients with clinically significant comorbidities so that the Results cannot be generalized to these patients. In addition, the safety of atogepant in pregnant women has not been evaluated.
“[A]togepant once a day was effective in reducing the number of migraine days and headache days in the preventive treatment of migraines over 12 weeks. The adverse events included constipation, nausea, and upper respiratory infections. Longer and larger studies are needed to determine the effectiveness and safety of atogepant for migraine prevention, ”the researchers concluded.
Disclosure: This research was supported by Allergan. For a full list of specifications, see the original reference.
Ailani J, Lipton RB, Goadsby PJ, et al. for the ADVANCE study group. Atogepant for the preventive treatment of migraines. N Engl J Med. 2021; 385 (8): 695-706. doi: 10.1056 / NEJMoa2035908