Effect of Galcanezumab Following Treatment Cessation in Patients With Migraine: Results From 2 Randomized Phase 3 Trials

Abstract

Objective: We examined the efficacy and safety of galcanezumab after treatment cessation in randomized double-blind, placebo-controlled, migraine prevention studies (EVOLVE-1; EVOLVE-2).

Background: Galcanezumab is indicated for migraine prevention in adults.

Methods: Adults with episodic migraine were enrolled into EVOLVE-1 and EVOLVE-2, which randomized 858 and 915 patients, respectively, to galcanezumab 120 mg (an initial 240-mg loading dose), galcanezumab 240 mg, or placebo, administered subcutaneously once monthly for 6 months. After treatment completion or discontinuation, patients entered a 4-month posttreatment period. Efficacy and safety from the posttreatment periods are reported.

Results: Overall, 740 patients (EVOLVE-1) and 830 (EVOLVE-2) patients entered the posttreatment periods, about 95% and 96% of patients, respectively, completed. In EVOLVE-1, change from pre-randomization baseline in monthly migraine headache days decreased over the posttreatment period from (mean [SE]) 5.2 (0.4) days (Month 6) to 4.1 (0.4) days (Month 10) for 120 mg and from 5.3 (0.4) days (Month 6) to 3.8 (0.4) days (Month 10) for 240 mg, and was stable for placebo (3.4 [0.3] days [Month 6] to 3.3 [0.3] days [Month 10]); differences between each galcanezumab dose group and placebo were statistically significant at each month, except for galcanezumab 240 mg at Month 10 (120 mg vs placebo: P < .001 Months 1-6, P = .007 Month 7, P = .044 Month 8, P = .016 Month 9, and P = .042 Month 10; 240 mg vs placebo: P < .001 Months 1-7, P = .015 Month 8, P = .021 Month 9, and P = .238 Month 10). EVOLVE-2 showed similar results. In both trials, there were no statistically significant differences between treatment groups and placebo for time-to-first loss of 50% response. During the posttreatment periods, 1.6% (EVOLVE-1) and 2.3% (EVOLVE-2) of patients initiated migraine preventive treatments. At Month 10, quality of life among galcanezumab-treated patients was similar to those taking placebo. The most common posttreatment emergent adverse event was upper respiratory tract infections. There were no discontinuations due to adverse events during the posttreatment periods.

Conclusions: Galcanezumab treatment effects were reduced during the posttreatment periods, but did not return to baseline. There were no unexpected adverse events after galcanezumab cessation.

Trial registration: ClinicalTrials.gov NCT02614183 NCT02614196.

Keywords: clinical trial; galcanezumab; migraine; posttreatment period; treatment cessation.

© 2019 Eli Lilly and Company.

Figures

Figure 1

Mean change from baseline in monthly migraine headache day (MHDs) in the treatment and posttreatment periods of EVOLVE‐1 (A) and EVOLVE‐2 (B). LS mean change ± SE is shown. P values are for the treatment vs placebo comparison. *P < .05; **P < .01; ***P < .001. GMB, galcanezumab; LS, least squares; SE, standard error.

Figure 2

Proportion of patients (50% responders) with at least 50% reduction from baseline in monthly migraine headache days (MHDs) at Months 6 and 10 of EVOLVE‐1 (A) and EVOLVE‐2 (B). The proportion of patients ± SE with a ≥50% reduction from baseline in MHDs (model estimated rate) is shown. *P < .05 vs PBO; **P ≤ .001 vs PBO. GMB, galcanezumab, MHD, migraine headache day; N, population size; PBO, placebo; SE, standard error.

Figure 3

Percentage of patients demonstrating first loss of 50% response from after double‐blind treatment of EVOLVE‐1 (A) and EVOLVE‐2 (B). The analysis includes patients who were 50% responders at the last month of the double‐blind treatment period and who also entered the posttreatment period. Patients who were sustained 50% responders during the entire posttreatment period were censored. GMB, galcanezumab; N, population size; PBO, placebo.

Figure 4

Mean change from baseline in monthly migraine headache days (MHD) with acute medication use during the treatment and posttreatment periods of EVOLVE‐1 (A) and EVOLVE‐2 (B). LS mean change ± SE is shown. *P < .05 vs PBO; **P < .01 vs PBO; ***P < .001 vs PBO. GMB, galcanezumab; LS, least squares; N, population size; PBO, placebo; SE, standard error.

Figure 5

Mean change from baseline in Migraine‐Specific Quality of Life Questionnaire (version 2.1) Role Function‐Restrictive Domain score at Months 6 and 10 of EVOLVE‐1 (A) and EVOLVE‐2 (B). LS mean change ± SE is shown. **P ≤ .001 vs PBO. GMB, galcanezumab; LS, least squares; N, population size; PBO, placebo; SE, standard error.