Abstract
Objective: To assess if there were any differential treatment effects in patients who had failed ≥2 previous preventives versus those who had not through a subgroup analysis of three Phase 3 studies of galcanezumab.
Background: Galcanezumab (GMB) is a humanized monoclonal antibody against calcitonin gene-related peptide under development for prevention of migraine.
Design/Methods: EVOLVE-1 (NCT02614183), EVOLVE-2 (NCT02614196) and REGAIN (NCT02614261) were Phase 3, randomized, double-blind, placebo-controlled studies in patients with episodic (EVOLVE-1/2) or chronic (REGAIN) migraine. Patients were randomized 2:1:1 to receive placebo, GMB_120 mg or GMB_240 mg during double-blind treatment period lasting six months (EVOLVE-1/2) or three months (REGAIN). Subgroup analysis was conducted for change from baseline in number of monthly migraine headache days (MHD) and ≥50% response (reduction in number of MHD) for patients who failed ≥2 prior preventive therapies (yes vs no). Subgroup-by-treatment interactions were calculated using linear or generalized linear mixed models.
Results: In the integrated analysis of EVOLVE studies and in the REGAIN study, GMB_120 mg/240 mg statistically significantly improved (p<0.001) overall mean reduction of monthly MHD compared with placebo in both subgroups of patients. For the subgroup who failed prior preventives, reductions were: EVOLVE: placebo: 0.81; GMB_120mg: 3.45; GMB_240mg: 3.85; REGAIN: placebo: 1.44; GMB_120mg: 5.91; GMB_240mg: 3.30. Significant treatment-by-subgroup interactions were seen for GMB_240mg (EVOLVE studies) and for GMB_120mg (REGAIN) suggesting better efficacy compared with placebo for these doses in patients who failed prior preventives. Mean percentage of patients with ≥50% response were significantly higher, compared with placebo, for both subgroups in EVOLVE studies and REGAIN study.
Conclusions: GMB_120mg/240mg is efficacious compared with placebo in reducing monthly MHDs in both patients who failed and did not fail ≥2 prior preventives. Treatment-by-subgroup interactions maybe driven by lower placebo response in patients who failed preventives previously as magnitude of change for GMB-treated patients were similar in both subgroups.
Study Supported by: Eli Lilly and Company
Disclosure: Dr. Zhang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly and Company. Dr. Zhang has received compensation for serving on the Board of Directors of Eli Lilly and Company. Dr. Ruff has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly and Company. Dr. Pearlman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly and Company. Dr. Govindan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly and Company. Dr. Aurora has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly and Company.
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