Fremanezumab as a preventive treatment for episodic and chronic migraine

ABSTRACT

Introduction: The importance of calcitonin gene-related peptide (CGRP) in migraine pathogenesis is well established. Fremanezumab is a humanized IgG2a monoclonal antibody that binds to CGRP.

Areas covered: In this paper, we review the development of fremanezumab, from early development into approval. The authors focus on the efficacy and safety of fremanezumab in both migraine stages. The authors highlight studies conducted in special populations and focus on unique aspects of its development, as well as on clinical pearls supported by the data.

Expert opinion: Fremanezumab was shown to be effective in episodic and chronic migraine, with a monthly and quarterly dose of administration, as monotherapy and add-on therapy. As with other monoclonal antibodies, the anti-CGRP onset of action was remarkably quick, and the effect seems to be maintained over time. No overt safety concerns emerged from the clinical studies, although long-term surveillance is necessary.

KEYWORDS:

• Headache
• CGRP
• fremenazumab
• migraine
• chronic migraine
• antibody

Article highlights

• Fremanezumab is a monoclonal antibody against CGRP which is effective for the preventive treatment of episodic and chronic migraine.

• Fremanezumab validated CGRP as a target for chronic migraine.

• As with the other antibodies anti-CGRP, fremanezumab demonstrated the quick onset of effect, separating from placebo within 1 week (and within one day in those with chronic migraine).

• It has shown clinically meaningful response by one month, measured by a decrease in the consumption of acute medication, and metrics of quality of life and disability.

• Fremanezumab is not limited by past failure to other preventive medications such as topiramate or botulinum toxin type A and demonstrated good safety and tolerability.

• It is the only approved antibody against CGRP that can be administered quarterly.

• Fremanezumab is effective in monotherapy and as an add-on.

• Since CGRP is a potent vasodilator and clinical studies, as comprehensive and careful as they are, are limited by the number of exposures, caution, and vigilance until post-marketing experience builds is suggested.

Declaration of interest

M Bigal was a full-time employee of Labrys (Chief Medical Officer) and of Teva (Chief Medical Officer and Chief Scientific Officer) and, as so, received salary and equity from both companies. He was directly involved with the development of fremanezumab at all stages. S Walter was a full-time employee at Labrys (Head of Preclinical Research and Clinical Pharmacology) and supported the transition of the program to Teva. AM Rapoport is a consultant and speaker to Teva pharmaceuticals and was a consultant to Labrys. He is an author on multiple phase 2 and phase 3 publications on the program. 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

A reviewer on this manuscript was an investigator on three phase 3 trials with fremanezumab in chronic migraine and cluster headache. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.