Reducing Episodic Cluster Headaches: Focus on Galcanezumab

Abstract

The involvement of calcitonin gene-related peptide in migraine and cluster headache has led to the recent development of new therapies. Galcanezumab, a novel monoclonal antibody targeting the calcitonin gene-related peptide, is approved for the migraine prevention and has recently been tested for the prevention of cluster headache. Two clinical trials have been conducted to investigate the efficacy and safety of galcanezumab in episodic cluster headache and chronic cluster headache. While efficacy endpoints were not met in the chronic subtype, galcanezumab reduced the weekly frequency of attacks in patients with episodic cluster headaches. In both studies, the antibody was well tolerated. This review summarizes and critically reviews the available data regarding the rationale behind targeting the calcitonin gene-related peptide with galcanezumab for the prevention of cluster headache.

Keywords:

• cluster headache
• calcitonin gene-related peptide
• CGRP
• antibody
• LY2951742

Abbreviations

5-HT, serotonin; 5-HT_1b, serotonin receptor 1B; 5-HT_1d, serotonin receptor 1D; ADAs, antidrug antibodies; AEs, adverse events; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; cCH, chronic cluster headache; eCH, episodic cluster headache; CGRP, calcitonin gene-related peptide; CH, cluster headache; CLR, calcitonin receptor-like receptor; DBF, dermal blood flow; FDA, Food and Drug Administration; PKC, protein kinase C; RAMP1, receptor activity-modifying protein 1; RCP, receptor component protein; SPG, sphenopalatine ganglion; TRPV1, transient receptor potential vanilloid 1; US, United States.

Author Contributions

Each author made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed on the journal to which the article will be submitted; reviewed and agreed on all versions of the article before submission, during revision, the final version accepted for publication, and any significant changes introduced at the proofing stage; as well as agree to be accountable for all aspects of the work.

Disclosure

MMK has acted as an invited speaker for Novartis and received travel grant from ElectroCore, LLC. MA is a consultant, speaker or scientific advisor for Allergan, Amgen, Alder, ATI, Eli Lilly, Novartis, and Teva, primary investigator for Alder, Amgen, Allergan, Eli Lilly, Novartis and Teva trials. MA has no ownership interest and does not own stocks of any pharmaceutical company. MA serves as associate editor of Cephalalgia, associate editor of Headache, co-editor of the Journal of Headache and Pain. MA is President of the International Headache Society. The authors report no other conflicts of interest in this work.

Additional information

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.