Weight Loss with Atogepant in the Long-Term Treatment of Migraine: an Interim Analysis of a Safety Endpoint from a Phase 3, Multicenter, Open-Label, 156-Week Extension Study.

OBJECTIVE:To assess weight loss with atogepant 60 mg once daily during long-term treatment of chronic migraine (CM) and episodic migraine (EM) among participants previously failed by two to four classes of conventional oral preventive medications. BACKGROUND:The risk of migraine, including CM, in individuals with obesity is higher than in those without obesity. Calcitonin gene-related peptide has been linked to the pathophysiology of both obesity and migraine. Weight loss with atogepant, a calcitonin gene-related peptide receptor antagonist indicated for the preventive treatment of migraine, has been observed during the 12-week EM and CM trials, as well as in long-term (40- or 52-week) EM trials. Long-term effects of atogepant on body weight in participants with increased migraine burden (i.e., EM or CM) have not been reported. METHODS:In this interim analysis of a safety endpoint from study 312, a phase 3, open-label, extension study, weight loss was assessed in the overall population and by prior participation in each lead-in study (12-week double-blind treatment period): PROGRESS (phase 3, multicenter, randomized, controlled study in CM) or ELEVATE (phase 3, multicenter, randomized, controlled study in EM treatment failure). Change from baseline in body weight at each study visit through end of treatment (PROGRESS and ELEVATE) or up to week 52 (study 312) was assessed (safety endpoint). Proportions of participants with ≥5% weight loss at any time, at the end of the lead-in study, or at week 52 in study 312 were evaluated. RESULTS:Participants from PROGRESS (n = 325) and ELEVATE (n = 270) rolled over to study 312 (n = 595) and were treated with atogepant 60 mg once daily. In study 312, mean (standard deviation) body weight decreased over time (-2.16 kg [5.89 kg; -4.76 lb] at week 52), with 44.8% (265/592) of participants experiencing a ≥5% weight loss at any time during the study and 29.5% (140/474) experiencing a ≥5% weight loss at week 52. In study 312, weight loss from lead-in study baseline was evident as early as week 4 and appeared to plateau around weeks 28 to 36, reaching a maximum numerical weight loss at week 44. Higher baseline body mass index was associated with greater odds of achieving ≥5% weight loss both at any time and at week 52. No significant effect of sex, race, adverse drug reactions, or therapeutic response to treatment was observed. CONCLUSIONS:Participants receiving atogepant 60 mg once daily for long-term preventive treatment of migraine were observed to have a decrease in mean body weight after 1 year of open-label treatment. Approximately 30% of participants experienced a clinically meaningful (≥5%) weight loss threshold after 1 year of open-label treatment. Future studies are needed to further characterize the mechanisms of weight loss associated with atogepant treatment.