Efficacy and safety of fremanezumab in patients with episodic and chronic migraine with documented inadequate response to 2 to 4 classes of migraine preventive medications over 6 months of treatment in the phase 3b FOCUS study

Abstract

Background: Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) selectively targets the calcitonin gene-related peptide and has proven efficacy for the preventive treatment of migraine. In this study, we evaluated the long-term efficacy, safety, and tolerability of monthly and quarterly fremanezumab.

Methods: Episodic migraine and chronic migraine patients completing the 12-week double-blind period of the FOCUS trial entered the 12-week open-label extension and received 3 monthly doses of fremanezumab (225 mg). Changes from baseline in monthly migraine days, monthly headache days of at least moderate severity, days of acute headache medication use, days with photophobia/phonophobia, days with nausea or vomiting, disability scores, and proportion of patients achieving a ≥50% or ≥75% reduction in monthly migraine days were evaluated.

Results: Of the 807 patients who completed the 12-week double-blind treatment period and entered the open-label extension, 772 patients completed the study. In the placebo, quarterly fremanezumab, and monthly fremanezumab dosing regimens, respectively, patients had fewer average monthly migraine days (mean [standard deviation] change from baseline: - 4.7 [5.4]; - 5.1 [4.7]; - 5.5 [5.0]), monthly headache days of at least moderate severity (- 4.5 [5.0]; - 4.8 [4.5]; - 5.2 [4.9]), days per month of acute headache medication use (- 4.3 [5.2]; - 4.9 [4.6]; - 4.8 [4.9]), days with photophobia/phonophobia (- 3.1 [5.3]; - 3.4 [5.3]; - 4.0 [5.2]), and days with nausea or vomiting (- 2.3 [4.6]; - 3.1 [4.5]; - 3.0 [4.4]). During the 12-week open-label extension, 38%, 45%, and 46% of patients, respectively, achieved a ≥50% reduction and 16%, 15%, and 20%, respectively, achieved a ≥75% reduction in monthly migraine days. Disability scores were substantially improved in all 3 treatment groups. There were low rates of adverse events leading to discontinuation (<1%).

Conclusion: Fremanezumab demonstrated sustained efficacy up to 6 months and was well tolerated in patients with episodic migraine or chronic migraine and documented inadequate response to multiple migraine preventive medication classes.

Trial registration: ClinicalTrials.gov NCT03308968 (FOCUS).

Keywords: CGRP; Calcitonin gene-related peptide; Long-term efficacy; Long-term safety; Migraine.

Conflict of interest statement

MA has received personal fees from AbbVie/Allergan, Amgen, Eli Lilly, Lundbeck, Novartis, and Teva Pharmaceuticals. MA is the principal investigator for ongoing AbbVie/Allergan, Amgen and Lundbeck trials. MA has no ownership interest and does not own stocks of any pharmaceutical company. MA serves as associate editor of Cephalalgia and associate editor of The Journal of Headache and Pain. MA is president of the International Headache Society (IHS). JMC, MG, VRC, SB, XN, YK, and LJ are employees of Teva Pharmaceuticals. H-CD has received honoraria for participation in clinical trials, contribution to advisory boards, or oral presentations from Alder BioPharmaceuticals, Allergan, Amgen, electroCore, Ipsen, Eli Lilly, Medtronic, Novartis, Pfizer, Teva Pharmaceuticals, and Weber & Weber; electroCore provided financial support for research projects. H-CD has received research support from the German Research Council, the German Ministry of Education and Research, and the European Union. H-CD serves on the editorial boards of Cephalalgia and The Lancet Neurology. H-CD chairs the Clinical Guidelines Committee of the German Society of Neurology and is a member of the Clinical Trials Committee of the IHS.

© 2021. The Author(s).

Figures

Fig. 1

FOCUS study design. PBO, placebo; EM, episodic migraine; CM, chronic migraine; V, visit; DB, double-blind; OLE, open-label extension

Fig. 2

Mean change from BL in the monthly average number of migraine days over 6 months (mITT).a BL, baseline; mITT, modified intent-to-treat; DB, double-blind; OLE, open-label extension. aAll patients in the OLE received fremanezumab 225 mg monthly

Fig. 3

Mean change from BL in the number of headache days of at least moderate severity in the DB period and the OLE (mITT).a BL, baseline; DB, double-blind; OLE, open-label extension; mITT, modified intent-to-treat. aAll patients in the OLE received fremanezumab 225 mg monthly

Fig. 4

Proportion of patients achieving a ≥50% reduction and b ≥75% reduction in the monthly average number of migraine days in the DB period and the OLE (mITT).a DB, double-blind; OLE, open-label extension; mITT, modified intent-to-treat. aAll patients in the OLE received fremanezumab 225 mg monthly

Fig. 5

Proportion of patients achieving ≥50% reduction in the monthly average number of migraine days over 6 months (mITT).a mITT, modified intent-to-treat; DB, double-blind; OLE, open-label extension. aAll patients in the OLE received fremanezumab 225 mg monthly

Fig. 6

Mean change from BL in days of acute headache medication use in the DB period and the OLE (mITT).a BL, baseline; DB, double-blind; OLE, open-label extension; mITT, modified intent-to-treat. aAll patients in the OLE received fremanezumab 225 mg monthly

Fig. 7

Mean change from BL in days with a photophobia/phonophobia and b nausea/vomiting in the DB period and the OLE (mITT).a BL, baseline; DB, double-blind; OLE, open-label extension; mITT, modified intent-to-treat. aAll patients in the OLE received fremanezumab 225 mg monthly

Fig. 8

Mean change in disability in the DB period and the OLE as measured by a HIT-6 and b MIDAS (mITT).a,b BL, baseline; DB, double-blind; OLE, open-label extension; HIT-6, Headache Impact Test; MIDAS, Migraine Disability Assessment; mITT, modified intent-to-treat. aAll patients in the OLE received fremanezumab 225 mg monthly