Positive Response to Galcanezumab Following Treatment Failure to OnabotulinumtoxinA in Patients With Migraine: Post hoc Analyses of 3 Randomized Double-Blind Studies.

Background and purpose Humanized monoclonal antibody galcanezumab, which binds to calcitonin-gene-related peptide, has shown efficacy for episodic and chronic migraine prevention. These analyses evaluated galcanezumab response for migraine headache prevention in patients who previously failed onabotulinumtoxinA ('nonresponse' or 'inadequate response' or safety reasons). Methods Post hoc analyses included data from three double-blind, placebo-controlled, phase 3 episodic or chronic migraine studies; 2886 patients randomly received 120 or 240 mg galcanezumab or placebo. During double-blind periods the study drug was administered subcutaneously once a month for 6 months in EVOLVE-1 and -2 and for 3 months in REGAIN. The 120 mg groups received a 240 mg loading dose at month 1. Pooled analyses included 129 patients who failed onabotulinumtoxinA. Using mixed effect model repeat measurements, the least squares mean change from baseline in the number of migraine headache days (MHDs) was calculated for the first 3 months of treatment. Results For pooled analyses, significant decreases from baseline in the number of MHDs were observed for 120 mg (-3.91) and 240 mg (-5.27) galcanezumab overall versus placebo (-0.88) across 3-month time points for patients who failed onabotulinumtoxinA. Corresponding data for patients with chronic migraine showed significant decreases: 120 mg (-3.18) and 240 mg (-4.26) galcanezumab versus placebo (0.16). Significant reductions in the number of MHDs per month with acute medication use included 120 mg galcanezumab (-4.35) and 240 mg galcanezumab (-4.55) versus placebo (-0.83). Estimates of >= 50% response during months 1-3 were 9.4% for placebo, 41.3% for 120 mg galcanezumab and 47.5% for 240 mg galcanezumab. Conclusion Galcanezumab is an option for prevention of migraine in patients who have previously failed onabotulinumtoxinA preventive therapy.