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

Abstract

Purpose

Fremanezumab monoclonal antibody therapy has demonstrated efficacy for chronic migraine (CM) with rapid onset and good tolerability. This subgroup analysis of two clinical trials (Japanese and Korean CM Phase 2b/3 [NCT03303079] and HALO CM Phase 3 [NCT02621931]) aimed to evaluate the efficacy and safety of fremanezumab in Japanese patients.

Patients and Methods

Both trials randomly assigned eligible patients at baseline (1:1:1 ratio) to subcutaneous monthly fremanezumab, quarterly fremanezumab, or placebo at 4-week intervals. The primary endpoint was the mean change from baseline in the monthly (28-day) average number of headache days of at least moderate severity during the 12-week period after the first dose of study medication (analyzed by ANCOVA over 12 weeks and MMRM over initial 4 weeks). Secondary endpoints examined other aspects of efficacy, including medication use and disability.

Results

A total of 479 and 109 patients were Japanese in the Japanese and Korean CM Phase 2b/3 and HALO CM trials, respectively. Baseline and treatment characteristics were generally similar between treatment groups for both trials. Results of subgroup analyses for the primary endpoint according to ANCOVA demonstrated the superiority of fremanezumab over placebo in Japanese patients (quarterly fremanezumab, p=0.0005; monthly fremanezumab, p=0.0002 in both trials). Results using the MMRM analysis confirmed the rapid onset of action in this population. Results of the secondary endpoints further supported the efficacy of fremanezumab in Japanese patients. Fremanezumab was well tolerated with nasopharyngitis and injection-site reactions representing the most common adverse events in all treatment groups.

Conclusion

Despite the limitations of subgroup analyses, these consistent results confirm the efficacy and tolerability of fremanezumab in Japanese patients with CM.

Keywords:

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

Data Sharing Statement

De-indentified 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.

Acknowledgments

We would like to thank all patients for their participation in the related 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.