A study has evaluated the efficacy, safety, and tolerability of Atogepant versus placebo in a phase 2b/3 trial for prevention of episodic migraine.
Atogepant is a novel, oral CGRP receptor antagonist in development for the prevention of migraine. It has high affinity at the human CGRP receptor (Ki=15–26 pM ) and approximately 100× lower affinity at the human AMY1 receptor, estimated terminal half-life approximately10 hours, and produces no apparent reactive metabolites.
Multicenter, randomized, double-blind, placebo-controlled, parallel-group trial has been carried out.
Adults with a history of migraine, with or without aura, and 4–14 migraine days in the 28-day baseline period were randomized 2:1:2:1:2:1 to placebo, Atogepant 10 mg QD, 30 mg QD, 30 mg BID, 60 mg QD, or 60 mg BID, respectively, and treated for 12 weeks.
Primary efficacy endpoint was change from baseline in mean monthly migraine days.
Safety and tolerability were evaluated.
Of 834 subjects randomized, 825 composed the safety population and 795 composed the efficacy population.
Mean age was 40.1 years; a majority was white ( 76.1% ), female ( 86.5% ), and had never taken preventive treatment for migraine ( 71.9% ).
Mean baseline migraine days were 7.67 ( SD=2.49 ).
Mean change in migraine days across the 12-week treatment period ( P values versus placebo ): placebo ( −2.85 ), Atogepant 10 mg QD ( −4.00, P=0.0236 ), 30 mg QD ( −3.76, P=0.0390 ), 30 mg BID ( −4.23, P=0.0034 ), 60 mg QD ( −3.55, P=0.0390 ), 60 mg BID ( −4.14, P=0.0031 ).
Treatment-emergent adverse effects were reported by 480 subjects ( 58.2% ); for 170 ( 20.6% ), the adverse effects were considered treatment-related.
Seven subjects ( 0.8% ) reported serious adverse effects, none considered treatment-related.
There were 10 cases of treatment-emergent ALT / AST elevations more than 3× the upper limit of normal, balanced across groups.
In conclusions, all 5 Atogepant treatment arms showed statistically significant, clinically relevant differences from placebo in reductions from baseline in mean migraine days.
Atogepant was well tolerated, with no treatment-related serious adverse effects. ( Xagena )
Goadsby PJ et al, Neurology 2019; 92 ( 15 Supplement )