Abstract text (incl. figure legends and references)

Objective: To evaluate the efficacy, safety, and tolerability of atogepant, an oral CGRP receptor antagonist, for the preventive treatment of chronic migraine (CM).

Methods: PROGRESS (NCT03855137) was a 12-week phase 3 trial in adults with CM, randomized 1:1:1 to atogepant (30mg twice daily [BID], 60mg once daily [QD]) or placebo. Primary efficacy endpoint was change from baseline in mean monthly migraine days (MMDs) over 12 weeks. A key secondary endpoint was proportion of participants with ≥50% reduction in 3-month average of MMDs.

Results: Of 778 participants (89.2% completed double-blind treatment period), 773 were in safety population (average age=42.1 years; average BMI=25.5 kg/m2; 87.6% female; 59.4% White; 36.4% Asian), and 755 in modified intent-to-treat (mITT) population. Baseline mean MMDs (mITT population) were 18.6 – 19.2 across groups. Mean change from baseline over 12 weeks was −7.5 days for atogepant 30mg BID, −6.9 for atogepant 60mg QD, and -5.1 for placebo (atogepant 30mg BID vs. placebo, p<0.0001, atogepant 60mg QD vs. placebo, p=0.0009). Reduction of ≥50% in 3-month average of MMDs was achieved by 42.7% of participants in the atogepant 30mg BID group, 41.0% in the atogepant 60mg QD group and 26.0% in the placebo group (30mg BID vs. placebo, p=0.0003, 60mg QD vs. placebo, p=0.0009). Treatment-emergent adverse events (TEAEs) were reported by 56.4% (atogepant 30mg BID), 63.2% (atogepant 60mg QD) and 49.4% (placebo) of participants. Most frequent TEAEs (≥5% any group): constipation (10.9% atogepant 30mg BID, 10.0% atogepant 60mg QD, 3.1% placebo); nausea (7.8% atogepant 30mg BID, 9.6% atogepant 60mg QD, 3.5% placebo). Serious TEAEs were reported by 1.6% (atogepant 30mg BID), 2.7% (atogepant 60mg QD) and 1.2% (placebo) of participants; none treatment-related.

Conclusion: Atogepant showed significant reductions in MMDs in participants with CM and was safe and generally well-tolerated.