Safety and tolerability of monthly galcanezumab injections in patients with migraine: integrated results from migraine clinical studies

Mark E Bangs, David Kudrow, Shufang Wang, Tina M Oakes, Gisela M Terwindt, Delphine Magis, Laura Yunes-Medina, Virginia L Stauffer, Mark E Bangs, David Kudrow, Shufang Wang, Tina M Oakes, Gisela M Terwindt, Delphine Magis, Laura Yunes-Medina, Virginia L Stauffer

Abstract

Background: Galcanezumab, a humanized monoclonal antibody that selectively binds to calcitonin gene-related peptide, has demonstrated a significant reduction in monthly migraine headache days in phase 2 and 3 trials. In these analyses, we aimed to evaluate the safety and tolerability of galcanezumab compared with placebo for prevention of episodic or chronic migraine.

Methods: Data were integrated from three double-blind clinical studies for the up to 6-month galcanezumab exposure group (N = 1435), and from five clinical studies for the up to 1-year all-galcanezumab exposure group (N = 2276). Patients received a monthly 120 mg subcutaneous injection of galcanezumab (with a 240 mg loading dose in month 1), 240 mg galcanezumab, or placebo. Outcomes measured were treatment-emergent adverse events (TEAEs), serious AEs (SAEs), and discontinuation due to AEs (DCAEs). Laboratory results, vital signs, electrocardiogram (ECG), suicidal ideation and behavior results were evaluated.

Results: TEAEs that occurred more frequently in galcanezumab-treated patients included injection site pain, injection site reactions excluding pain, constipation, vertigo, and pruritus. The proportion of DCAEs among galcanezumab-treated patients ranged between 1.8 and 3.0%, and differed from placebo group for galcanezumab 240 mg (P < 0.05). Fewer than 2.0% of patients in either galcanezumab dose-group compared with 1.0% of placebo-treated patients reported a SAE. There were no clinically meaningful differences between galcanezumab and placebo in laboratory measures, vital signs including blood pressure, ECGs, cardiovascular-related AEs, or suicidal ideation and behavior.

Conclusions: Galcanezumab demonstrated a favorable safety and tolerability profile for up to 1 year of treatment for the prevention of migraine.

Trial registration: Clinical Trials CGAB = NCT02163993, EVOLVE-1 = NCT02614183, EVOLVE-2 = NCT02614196, REGAIN = NCT02614261, and CGAJ = NCT02614287. All were first posted on 25 November 2015, except CGAB posted on 16 June 2014, and before enrolling the first patient.

Keywords: CGRP; Galcanezumab; Migraine; Safety; Tolerability.

Conflict of interest statement

MEB, SW, TMO, LY-M, and VLS are full-time employees of Eli Lilly and Company, and minor stockholders of the sponsor of the work, Eli Lilly and Company. DK has received consultant fees from Alder and Amgen; speaker fees from Teva; grants from Eli Lilly and Company, during the conduct of the study; and grants from Amgen, Teva, Alder, Biohaven, Roche, and VM Biopharma, outside the submitted work. GMT reports personal fees from Eli Lilly and Company, Teva Pharmaceuticals, and Novartis, during the conduct of the study and grants from Dutch Brain Foundation, Dutch Heart Foundation, and Netherlands Organization for Scientific Research (NWO), outside the submitted work. DM reports ad hoc advisory board fees from Novartis Belgium NV and Eli Lilly Benelux. DM is also a member of the editorial board of BMC Neurology and Cephalalgia. The authors received article support from Medtronic Europe and Cefaly Technology.

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