Drug profile: galcanezumab for prevention of cluster headache

ABSTRACT

Introduction: Cluster headache [CH] is a severely disabling trigeminal autonomic cephalalgia [TAC]. Approximately 1 in 1,000 adults are affected by CH. Calcitonin gene-related peptide [CGRP] is an important mediator in the pathophysiology of CH. Galcanezumab is a monoclonal antibody with an affinity for the CGRP peptide, FDA approved for the prevention of episodic CH.

Areas covered: Search words queried were ‘cluster headache,’ ‘cluster headache, and CGRP,’ ‘cluster headache, and galcanezumab.’ Over 99 articles in Pubmed and prescribing information for galcanezumab were reviewed. Some of the data pertaining to CH trials with fremanezumab were reviewed using clinical trials.org.

Expert opinion: Galcanezumab has shown benefit in decreasing the weekly frequency of CH attacks across week 1 through week 3 in patients with CH; 8.7 attacks in the galcanezumab group, as compared with 5.2 in the placebo group (95% confidence interval, 0.2 to 6.7; P = 0.04). It has a favorable risk-benefit ratio. The prevention of CH with CGRP inhibition represents a novel advance for a condition with a significant unmet need. The negative trial results of galcanezumab for chronic cluster headache [CCH] may be due to the refractory nature and sheds light on the critical need to investigate the underlying biology and therapeutic options.

KEYWORDS:

• Cluster headache
• chronic cluster headache
• calcitonin gene-related peptide
• immunomodulation
• antibody
• galcanezumab
• LY2951742
• treatment

Article highlights

• Cluster headache [CH] is a type of trigeminal autonomic cephalalgia, characterized by disabling pain occurring in 1 in 1,000 adults.

• Established therapies include oxygen, some triptans, and non-invasive vagus nerve stimulation for the treatment of acute attacks.

• Adverse side effect profiles and tolerability limit the off-label use of preventive therapies such as verapamil and lithium.

• CGRP release is associated with trigeminovascular activation during acute cluster attacks.

• Galcanezumab is a humanized monoclonal antibody that binds to CGRP and blocks its binding to the CGRP receptor.

• Galcanezumab is the first FDA approved preventive treatment for episodic CH based on a phase III multi-center, randomized, placebo-controlled trial showing efficacy in the primary outcome measure: mean change from baseline in a number of weekly CH attacks.

• The chronic cluster headache [CCH] study was negative for primary and secondary endpoints.

• Side effects of galcanezumab include injection site and hypersensitivity reactions.

• Galcanezumab is not metabolized by the cytochrome P450 enzymes; therefore, drug–drug interactions are unlikely.

• There remains an unmet need for the prevention of CCH.

• Long-term safety, tolerability, and efficacy studies are needed for prolonged use.

Declaration of interest

T Monteith was a site investigator for the two-phase III randomized, double-blind, placebo-controlled study of galcanezumab in patients with both episodic and chronic cluster headache. She has served on advisory boards for Eli Lilly, Alder/Lundbeck, Impel NeuroPharma, Teva, Amgen, Biohaven, and Electrocore. She has received funding from educational grants from Eli Lilly, Amgen, and Alder. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.