Abstract text (incl. figure legends and references)

Objective:To evaluate mean monthly migraine day (MMD) responder rates to characterize the efficacy profile of atogepant in the preventive treatment of chronic migraine (CM).

Methods:PROGRESS was a multicenter, randomized, double-blind, placebo-controlled phase 3 study that assessed the safety, tolerability, and efficacy of atogepant 30 mg twice daily (BID) and 60 mg once daily (QD) compared with placebo for the preventive treatment of CM. Adults (18-80 years) with a ≥1-year history of CM and confirmation of ≥15 monthly headache days and ≥8 MMDs during the baseline period were randomized 1:1:1 to receive placebo, atogepant 30 mg BID, or atogepant 60 mg QD. These analyses evaluated ≥30%, ≥50%, ≥75%, and 100% reductions in mean MMDs across 12 weeks and at 4-week intervals. All reported P values are nominal; there was no adjustment for multiplicity.

Results:A total of 778 participants were randomized to treatment. The modified intent-to-treat population included 755 participants: placebo: n=246; atogepant 30 mg BID: n=253; and atogepant 60 mg QD: n=256. Atogepant-treated participants (30 mg BID and 60 mg QD) were significantly more likely than placebo-treated participants, respectively, to experience a ≥30% (62.1% and 59.0% vs 43.1%; P<0.001), ≥50% (42.7% and 41.0% vs 26.0%; P<0.001), or ≥75% (21.3% and 18.8% vs 5.7%; P<0.001) reduction in mean MMDs across 12 weeks. During weeks 1-4 and 5-8, the proportion of participants experiencing a ≥30% or ≥50% reduction in mean MMDs was significantly greater for both atogepant doses vs placebo and during weeks 9-12 for atogepant 30 mg BID vs placebo (Figure). The proportion of participants experiencing a ≥75% or 100% response was higher for both doses of atogepant in each 4-week interval assessed.

Conclusions:Both atogepant dosing regimens increased the proportions of participants with CM achieving ≥30%, ≥50%, ≥75%, or 100% reduction in mean MMDs across 12 weeks.