Poster Number-29 - Atogepant for the preventive treatment of chronic migraine: results from the PROGRESS phase 3 trial

The objective of this study was to evaluate the efficacy, safety, and tolerability of atogepant 30 mg twice daily (BID) and atogepant 60 mg once daily (QD) for the preventive treatment of chronic migraine. Atogepant is an oral, small-molecule calcitonin gene–related peptide receptor antagonist approved in the United States for the preventive treatment of episodic migraine.

Methods: PROGRESS (NCT03855137) was a randomized, double-blind, placebo-controlled, parallel-group, phase 3 trial conducted across North America, Europe, and East Asia. Participants were adults (18-80 years) with a history of chronic migraine (≥1 year) who had ≥15 headache days per month in the 3 months prior to screening and ≥15 headache days, of which ≥8 were migraine days, during the 4-week baseline screening period. Participants were randomized 1:1:1 to atogepant 30 mg BID, atogepant 60 mg QD, or placebo for 12 weeks. The primary efficacy endpoint was change from baseline in mean monthly migraine days (MMDs) across the 12-week treatment period. A key secondary endpoint was the proportion of participants with ≥50% reduction in the 3-month average of MMDs.

Results: There were 778 participants randomized (89.2% completed the double-blind treatment period); 773 were included in the safety population and 755 in the modified intent-to-treat (mITT) population. Participants in the safety population were on average 42.1 years old with a mean body mass index of 25.5 kg/m²; the majority were female (87.6%), 59.4% were White, and 36.4% were Asian. Based on the mITT population, baseline mean MMDs ranged from 18.6-19.2 across groups. The mean change from baseline across the 12-week treatment period was −7.5 days with atogepant 30 mg BID, −6.9 days with atogepant 60 mg QD, and −5.1 days with placebo (atogepant 30 mg BID vs placebo, P< 0.0001; atogepant 60 mg QD vs placebo, P=0.0009; adjusted for multiple comparisons). A reduction of ≥50% in the 3-month average of MMDs was achieved by 42.7% (108/253) of participants in the atogepant 30 mg BID group, 41.0% (105/256) in the atogepant 60 mg QD group, and 26.0% (64/246) in the placebo group (30 mg BID vs placebo, P=0.0003; 60 mg QD vs placebo, P=0.0009; adjusted for multiple comparisons). Statistically significant improvements were also achieved across all other secondary endpoints with atogepant 30 mg BID and 60 mg QD. Treatment-emergent adverse events (TEAEs) were reported by 56.4% receiving atogepant 30 mg BID, 63.2% receiving atogepant 60 mg QD, and 49.4% receiving placebo. The most frequently reported TEAEs (≥5% in any group) were constipation (10.9% atogepant 30 mg BID, 10.0% atogepant 60 mg QD, 3.1% placebo) and nausea (7.8% atogepant 30 mg BID, 9.6% atogepant 60 mg QD, 3.5% placebo). Treatment-emergent serious adverse events were reported by 1.6% receiving atogepant 30 mg BID, 2.7% receiving atogepant 60 mg QD, and 1.2% receiving placebo; none were considered treatment related.

Conclusion: Atogepant 30 mg BID and 60 mg QD demonstrated statistically significant reductions in mean MMDs among participants with chronic migraine. Atogepant was safe and generally well tolerated, consistent with the known safety profile of atogepant.

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