Galcanezumab for the prevention of cluster headache

ABSTRACT

Introduction

Cluster headache (CH) is among the worst painful conditions. The available therapies are scarce and not specific, leaving many patients unsatisfied because of poor efficacy and/or tolerability. Patients not responding to common treatments are offered semi-invasive and invasive procedures with uncertain results. Based on the current understanding of CH pathophysiology, new possible therapeutic approaches come from drugs interfering with Calcitonin Gene Related Peptide (CGRP).

Areas covered

After summarizing the evidence for CGRP involvement in CH pathophysiology, we review the published literature (PubMed) and information (clinicaltrials.gov, EudraCT, EMA and FDA websites) regarding a novel anti-CGRP monoclonal antibody, Galcanezumab, its pharmacological properties, development, and evidence for the treatment of CH. Publications regarding other indications (migraine) are considered for completeness and safety/tolerability profile.

Expert opinion

In one randomized clinical trial, Galcanezumab has proven to be effective and safe as a preventive treatment in episodic CH, with a favorable tolerability profile offering a potential new option in the therapeutic arsenal. Inefficacy of galcanezumab in chronic CH as well as the inefficacy of another monoclonal antibody against CGRP (fremanezumab) in both episodic and chronic CH question the scalability of the drug in CH management. Further, studies comparing galcanezumab to the current standard treatments are highly desirable.

KEYWORDS:

• Calcitonin gene-related peptide (CGRP)
• cluster headache
• galcanezumab
• monoclonal antibodies
• preventive treatment

Article Highlights

• Cluster headache is a severe condition with a high need of effective, safe and well tolerated preventive therapies.

• Galcanezumab is a monoclonal antibody against Calcitonin Gene Related Peptide (CGRP) aimed to treat neurovascular headaches such as migraine and cluster headache.

• In one phase 3 trial on episodic cluster headache patients galcanezumab was superior to placebo in reducing headache frequency.

• Galcanezumab was not effective for the treatment of chronic cluster headache.

• Another monoclonal antibody against CGRP (fremanezumab) was not effective in episodic and chronic cluster headache. Methodological issues could explain the difference with galcanezumab in episodic cluster headache.

• The Food and Drug Administration approved galcanezumab in the prevention of episodic cluster headache, while European Medicines Agency required more investigations.

• Galcanezumab has the potential to expand the therapeutic options to prevent episodic cluster headache particularly in non responders or in patients affected by side effects from prophylactic treatments.

• The different responsiveness to galcanezumab in episodic and chronic cluster headache suggests a different role of CGRP in the two conditions.

This box summarizes key points contained in the article.

Declaration of interest

M Leone has received honoraria for acting on advisory boards for Eli Lilly and TEVA. L Giani has received funding by the Italian Ministry of Health [Research project RF-2016-02364909]. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One of the reviewers on this paper has received honoraria for consulting and lectures within the past three years from Allergan Pharma, Astra Zeneca, Hormosan Pharma, Lilly Germany, Novartis Pharma, Sanofi Aventis, and TEVA. Peer reviewers on this manuscript had no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is funded by Ministero della Salute RF-2016-02364909.