Randomised, controlled trial of erenumab for the prevention of episodic migraine in patients from Asia, the Middle East, and Latin America: The EMPOwER study

Abstract

Objective: EMPOwER, a double-blind, randomised, phase 3 study, evaluated the efficacy and safety of erenumab in adults with episodic migraine from Asia, the Middle East, and Latin America.

Methods: Randomised patients (N = 900) received monthly subcutaneous injections of placebo, erenumab 70 mg, or 140 mg (3:3:2) for 3 months. Primary endpoint was change from baseline in monthly migraine days at Month 3. Other endpoints included achievement of ≥50%, ≥75%, and 100% reduction in monthly migraine days, change in monthly acute migraine-specific medication treatment days, patient-reported outcomes, and safety assessment.

Results: At baseline, mean (standard deviation) age was 37.5 (9.9) years, 81.9% were women, and monthly migraine days was 8.2 (2.8). At Month 3, change from baseline in monthly migraine days (primary endpoint) was -3.1, -4.2, and -4.8 days for placebo, erenumab 70 mg, and erenumab 140 mg, respectively, with a statistically significant difference for erenumab versus placebo (P = 0.002 [70 mg], P < 0.001 [140 mg]). Both erenumab doses were also significantly superior to placebo on all secondary endpoints, including the proportion of patients achieving ≥50% reduction from baseline in monthly migraine days, change from baseline in monthly acute migraine-specific medication treatment days and change from baseline in the Headache Impact Test-6™ scores. The safety profile of erenumab was comparable with placebo; no new safety signals were observed.

Conclusions: This study of erenumab in patients with episodic migraine from Asia, the Middle East, and Latin America met all primary and secondary endpoints. A consistent numerical benefit was observed with erenumab 140 mg versus erenumab 70 mg across all efficacy endpoints. These findings extend evidence of erenumab's efficacy and safety to patients under-represented in previous trials.ClinicalTrials.gov identifier: NCT03333109.

Keywords: Asia; Latin America; calcitonin gene-related peptide; episodic migraine; erenumab; randomised controlled trial.

Conflict of interest statement

Declaration of Conflicting Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Shuu-Jiun Wang has served on the advisory boards of Eli Lilly and Taiwan Novartis. He has received honoraria as a moderator from AbbVie, Pfizer, Eli Lilly, Bayer, and Eisai and has been the principal investigator of the clinical trials sponsored by Eli-Lilly, Novartis, and AbbVie. He has received research grants from the Taiwan Minister of Technology and Science, Brain Research Center, National Yang Ming Chiao Tung University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan, Taipei Veterans General Hospital, and Taiwan Headache Society.

Artemio A Roxas Jr. received personal fees from Novartis, during the conduct of the study.

Bibiana Saravia, Naji Riachi, Mei-Ling Sharon Tai, Surat Tanprawate, and Tai Tran Ngoc declare that there is no conflict of interest.

Byung-Kun Kim received personal fees from Eli Lilly Korea, personal fees from Teva Korea, personal fees from Lundbeck Koreas, personal fees from Yuyu Pharm, personal fees from SK chemical, personal fees from National Pension Service, outside the submitted work.

Debashish Chowdhury received grants and non-financial support from Novartis, during the conduct of the study; grants and non-financial support from Eli Lilly.

Zhao Yi Jing has served on the advisory boards of Teva and DKSH. She has received honoraria from Teva, DKSH and Novartis.

Daniel D Mikol is an employee of, and holds stocks in, Amgen.

Shaloo Pandhi, Peggy Hours-Zesiger, Shihua Wen, are employees of, and hold stocks in, Novartis.

Subhayan Mondal is an employee of Novartis.

Nadia Tenenbaum was an employee of Novartis at the time of conduct of this study and writing this research manuscript.

Figures

Figure 1.

Study design. n, patients who entered the safety follow-up phase; N, number of patients randomised; QM, every 4 weeks; SC, subcutaneous.

Figure 2.

Trial profile (randomised analysis set). A patient is defined as completer for the DBTP, if completed all DBTP visits and performed End of Trial assessment. A patient is defined as DBTP discontinuer if patient status is not ticked as “Completed” for study disposition page during DBTP or if he missed any DBTP visit. A patient is defined as completer for the study if patient status is ticked as “Completed” for the study disposition page (if completed the safety follow-up visit at week 24). Patients who entered the safety follow-up period are those who completed the End of Trial visit and did not discontinue study at that visit. Five patients discontinued from DBTP and still entered safety follow-up. Six randomised patients did not take study medication and not formally entered into DBTP. DBTP, double-blind treatment phase.

Figure 3.

Change from baseline in monthly migraine days by treatment and visit (modified intention-to-treat analysis set). Error bars represent the standard error. Intention-to-treat analysis set included all patients who were randomised in the study. P 

Figure 4.

Proportion of patients with: (a) ≥50% reduction from baseline in monthly migraine days, (b) ≥75% reduction from baseline in monthly migraine days, and (c) 100% reduction from baseline in monthly migraine days (modified intention-to-treat analysis set). Statistical analysis utilises a Cochran-Mantel-Haenszel test adjusting for stratification factor after missing data are imputed as non-response. Intention-to-treat analysis set included all patients who were randomised in the study. P