A Randomized Phase 2 Study of Erenumab for the Prevention of Episodic Migraine in Japanese Adults

Abstract

Objective: A phase 2, double-blind, placebo-controlled study to evaluate the efficacy and safety of erenumab for the prevention of episodic migraine in Japanese patients was conducted.

Background: Previous global clinical studies have demonstrated the efficacy of erenumab in the prevention of migraine.

Methods: Patients were randomized to placebo or erenumab 28, 70, or 140 mg administered subcutaneously once per month for 6 months. The primary endpoint was change from baseline in mean monthly migraine days over months 4-6 of the double-blind treatment phase. Secondary endpoints included the proportion of patients achieving ≥50% reduction from baseline in mean monthly migraine days (≥50% response) and change from baseline in mean monthly acute migraine-specific medication treatment days (MSMD) and mean Headache Impact Test (HIT-6™) scores. Efficacy outcomes were also determined at months 1, 2, and 3.

Results: Four hundred and seventy five patients were randomized 2:1:2:2 to placebo and erenumab 28, 70, and 140 mg, respectively. Greater reductions in monthly migraine days were observed for erenumab vs placebo with differences of -1.25 (95% CI: -2.10 to -0.41; P = .004), -2.31 (95% CI: -3.00 to -1.62; P < .001), and -1.89 (95% CI: -2.58 to -1.20; P < .001) days for erenumab 28, 70, and 140 mg. The odds of having a ≥50% response were 3.2, 5.6, and 4.7 times greater for erenumab 28 mg (95% CI: 1.30-7.88; P = .009), 70 mg (95% CI: 2.60-12.06; P < .001), and 140 mg (95% CI: 2.24-9.99; P < .001) than for placebo. Greater reductions from baseline in mean acute monthly MSMD were observed for erenumab vs placebo with differences of -1.07 (95% CI: -1.80 to -0.35; P = .004), -2.07 (95% CI: -2.66 to -1.49; P < .001), and -2.04 (95% CI: -2.63 to -1.45; P < .001) days for erenumab 28, 70, and 140 mg. Erenumab 70 and 140 mg also resulted in greater improvements in HIT-6™ scores. The safety profile was similar across treatment groups. The most common adverse event was nasopharyngitis, which occurred in 29.4% of patients in the placebo group and 28.9%-33.3% of patients in the erenumab groups.

Conclusion: Monthly subcutaneous injections of erenumab 70 mg demonstrated statistically significant and numerically maximal efficacy with a favorable safety profile, suggesting that erenumab is a potential new therapy for migraine prevention in Japan.

Trial registration: ClinicalTrials.gov NCT02630459.

Keywords: episodic migraine; erenumab; headache; migraine prevention; phase 2 trial.

© 2019 Amgen Inc. Headache: The Journal of Head and Face Pain published by Wiley Periodicals, Inc. on behalf of American Headache Society.

Figures

Figure 1

Flow of patients through the DBTP of the study. Patients were enrolled between January 6, 2016 and April 10, 2017, and the last patient completed the DBTP on October 2, 2017. Double‐blind treatment phase (DBTP); investigational product (IP).

Figure 2

Change from baseline in MMD. Data are shown as LSM with 95% CIs. The gray‐shaded area represents months 4‐6. Confidence interval (CI); least squares mean (LSM); monthly migraine days (MMD). *Denotes statistical significance.

Figure 3

Patients achieving ≥50% reduction from baseline in MMD. Data are shown as percentages. The gray‐shaded area represents months 4‐6. Monthly migraine days (MMD); odds ratio (OR). *Denotes statistical significance.

Figure 4

Change from baseline in MSMD. Data are shown as LSM with 95% CIs. The gray‐shaded area represents months 4‐6. Confidence interval (CI); least squares mean (LSM); migraine‐specific medication treatment days (MSMD). *Denotes statistical significance.