Fremanezumab for Episodic Migraine Prevention in Japanese Patients: Subgroup Analysis from Two International Trials

Abstract

Purpose

The monoclonal antibody fremanezumab has been shown effective and well tolerated in numerous Phase 2 and Phase 3 trials. This subgroup analysis of the international HALO episodic migraine (EM; [NCT02629861]) trial and a similarly designed phase 2b/3 trial in Japanese and Korean patients (NCT03303092) sought to evaluate the efficacy and safety of fremanezumab in Japanese patients with EM.

Patients and Methods

In both trials, eligible patients were randomly assigned at baseline to receive subcutaneous monthly fremanezumab, quarterly fremanezumab, or placebo in a 1:1:1 ratio. The primary endpoint was the mean change from baseline in the monthly (28-day) average number of migraine days during the 12-week period after the first dose of fremanezumab or placebo. Secondary endpoints assessed other aspects of efficacy, including disability and medication use.

Results

A total of 301 patients in the Japanese and Korean phase 2b/3 trial and 75 patients in the HALO EM trial were Japanese with baseline and treatment characteristics similar between treatment groups. According to ANCOVA analysis of the primary endpoint, both fremanezumab quarterly and monthly led to greater reductions in the monthly (28-day) average number of migraine days than placebo. This was supported by MMRM analysis of the primary endpoint over the initial 4 weeks, highlighting the rapid onset of action of fremanezumab. Results of secondary endpoint analysis supported the primary endpoint analyses. Fremanezumab was well tolerated with no new safety signals seen in this population of Japanese patients.

Conclusion

Fremanezumab appears to be an effective and well-tolerated preventive medication for Japanese patients with EM.

Keywords:

• calcitonin gene-related peptide
• episodic migraine
• fremanezumab
• Japanese

Data Sharing Statement

De-identified individual participant data underlying the results of this analysis as well as relevant study protocols may be shared with researchers to achieve aims prespecified in a methodologically sound research proposal upon request to the corresponding author (Masami Nakai).

Acknowledgments

We would like to thank all patients for their participation in the trials, and all trial sites, investigators, and all clinical research staff for their contributions. We also thank Yoshiko Okamoto, PhD, and Mark Snape, MBBS, of inScience Communications, Springer Healthcare, for helping write the outline and first draft of the manuscript. This medical writing assistance was funded by Otsuka Pharmaceutical Co., Ltd.

Disclosure

KS has received grants from Sumitomo Pharma Co., Ltd.; consulting fees from Takeda Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd.; payment for lectures from AMGEN Inc., Daiichi Sankyo Company, Eisai Co., Ltd., Eli Lilly Japan, Otsuka Pharmaceutical Co., Ltd., Sanofi Japan, Sumitomo Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd.; committee member for Japanese Society of Headache, Japanese Society of Human Genetics. TT has received honoraria for lectures from Eisai Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Amgen K.K., Eli Lilly and Company, Daiichi Sankyo; research funds under contract from Eisai Co., Ltd., Eli Lilly and Company, Amgen K.K., Allergan Japan K.K., Shionogi & Co., Ltd., Lundbeck Japan K.K. MN, YS, MI, YI, and NK are full-time employees of Otsuka Pharmaceutical Co., Ltd. XN and SB are full-time employees of Teva Branded Pharmaceutical Products. The authors report no other conflicts of interest in this work.