Efficacy of galcanezumab in patients with episodic migraine and a history of preventive treatment failure: results from two global randomized clinical trials

Abstract

Background and purpose: The efficacy of galcanezumab, a monoclonal antibody for migraine prevention, has been demonstrated in two pivotal trials in patients with episodic migraine. Methods: EVOLVE-1 and EVOLVE-2 were identical phase 3, randomized, double-blind, placebo-controlled studies in patients with episodic migraine. Mean migraine headache days per month at baseline was 9. Patients were randomized 2:1:1 to monthly injections of placebo, galcanezumab 120 mg/240 mg during the 6-month double-blind treatment period. Key efficacy outcomes were assessed in subgroups amongst patients for whom, previously, for efficacy and/or safety/tolerability reasons (i) one or more (≥1) preventives failed, (ii) two or more (≥2) preventives failed and (iii) preventives were never used, or used but not failed (no prior failure). Results: In an integrated analysis of EVOLVE studies, galcanezumab 120 mg/240 mg versus placebo led to larger overall mean (SE) reductions in monthly migraine headache days across 6 months in patients with prior preventive failures (P < 0.001): ≥1 failure: 120 mg: −4.0 (0.4); 240 mg: −4.2 (0.5); placebo: −1.3 (0.4); ≥2 failures: 120 mg: −3.1 (0.7); 240 mg: −3.8 (0.8); placebo: −0.5 (0.6). Similar results were observed amongst patients with no prior failure, but the placebo response was larger: 120 mg: −4.7 (0.2); 240 mg: −4.5 (0.2); placebo: −3.0 (0.2) (P < 0.001 versus placebo). Significant improvements were observed with galcanezumab versus placebo for ≥50% and ≥75% reduction in monthly migraine headache days. Conclusion: In patients with episodic migraine treated with galcanezumab, those with ≥1 or ≥2 prior preventive failures had significantly larger improvements, versus placebo, in efficacy outcomes. Similar results were observed in patients with no prior failure, with a larger placebo response.