Early onset of efficacy with fremanezumab in patients with episodic and chronic migraine: subanalysis of two phase 2b/3 trials in Japanese and Korean patients

Abstract

Background: Early onset of action has become recognized as an important efficacy feature of preventive migraine treatment, which can help overcome adherence issues commonly associated with older medications. Preventive treatments that target the calcitonin gene-related peptide (CGRP) or the CGRP receptor have been previously shown to provide early onset of action.

Methods: This subanalysis of primary endpoints of two separate phase 2b/3 studies sought to determine the onset of action of fremanezumab in Japanese and Korean patients with episodic migraine (EM) and chronic migraine (CM).

Results: In EM patients (n = 357), both fremanezumab quarterly and fremanezumab monthly led to greater reductions in weekly migraine days (days/week) than placebo from the first week after the initial injection and thereafter during the remainder of the study period. Similarly, CM patients (n = 571) had a greater reduction in headache days of at least moderate severity (days/week) with fremanezumab (total) than placebo. The percentage of patients with a migraine day (EM) or headache day at least moderate severity (CM) was lower in those treated with fremanezumab than placebo and this effect was apparent from as early as Day 2 (1 day after first injection).

Conclusions: These results suggest that fremanezumab has an early onset of action, as noted in previous post hoc analyses of anti-CGRP monoclonal antibodies.

Trial registration: ClinicalTrials.gov. NCT03303092 , Registered 5 October 2017, NCT03303079 , Registered 5 October 2017.

Keywords: Calcitonin gene-related peptide; Chronic migraine; Early onset; Episodic migraine; Fremanezumab; Japanese; Korean.

Conflict of interest statement

TT has received grants or contracts from Eisai Co., Ltd. Amgen Inc., Eli Lilly Japan K.K., Allergan Japan K.K.; consulting fees from Otsuka Pharmaceutical Co., Ltd.; honoraria for lectures from Otsuka Pharmaceutical Co., Ltd., Eisai Co., Ltd., Amgen Inc., and Eli Lilly Japan K.K. B-KK reports personal fees from Otsuka Pharmaceutical Co., Ltd.; consultation fees from Teva Korea and Sanofi Korea; consultation and lecture fees from Lundbeck Korea; and lecture fees from Lilly Korea, Allergan Korea, SK-Pharma, and YuYu Pharma Inc. XN is a full-time employee of Teva Branded Pharmaceutical Products R&D. MN, YS, MI, and NK are full-time employees of Otsuka Pharmaceutical Co., Ltd.

© 2022. The Author(s).

Figures

Fig. 1

Study schema in CM and EM patients

Fig. 2

Change in (A) MMD and (B) WMD in EM patients. Change in MMD represents mean change from baseline during the 4-week period from the first dose (ANCOVA analysis) while change in WMD represents mean change per week during the 4-week period from the first dose (MMRM analysis). An asterisk denotes P < 0.05 and a dagger P < 0.0001 for the comparison with placebo. Abbreviations: ANCOVA, analysis of covariance; LSM, least-squares mean; MMD, monthly migraine days; MMRM, mixed-effects model for repeated measures; WMD, weekly migraine days

Fig. 3

Change in (A) monthly and (B) weekly average headache days of at least moderate severity in CM patients. Change in monthly average number of headache days of at least moderate severity represents mean change from baseline during the 4-week period after the first dose (ANCOVA analysis) while change in the weekly average number of headache days of at least moderate severity represents mean change per week during the 4-week period from the first dose (MMRM analysis). An asterisk denotes P < 0.05 and a dagger P < 0.0001 for the comparison with placebo. Fremanezumab is the sum of fremanezumab monthly and fremanezumab quarterly groups. Abbreviations: ANCOVA, analysis of covariance; LSM, least-squares mean; MMRM, mixed-effects model for repeated measures

Fig. 4

Percentage of EM patients reporting a migraine during a day from Day 1 to 7. Day 1 is the day of injection of study medications. P < 0.05 for difference with placebo from Day 1–7 for fremanezumab quarterly and from Day 2–7 for fremanezumab monthly

Fig. 5

Percentage of CM patients reporting a headache during a day from Day 1 to 7. Headache in CM patients was defined as those of at least moderate severity. Day 1 is the day of injection of study medications. Fremanezumab is the sum of fremanezumab monthly and fremanezumab quarterly groups. P < 0.05 for difference with placebo from Day 2–7 for fremanezumab