Monoclonal antibodies for the prevention of migraine

ABSTRACT

Introduction: Calcitonin Gene-Related Peptide (CGRP) plays a crucial role in migraine pathophysiology. A novel specific treatment strategy for the prevention of migraine incorporates monoclonal antibodies (mAbs) against CGRP and its canonical receptor. Eptinezumab, fremanezumab and galcanezumab block CGRP mediated effects by binding to the peptide, while erenumab blocks the CGRP receptor.

Areas covered: Following a brief overview of pharmacological characteristics, we will review phase III trials for the use of CGRP mAbs in the prevention of episodic and chronic migraine.

Expert opinion: All four CGRP mAbs demonstrated an excellent safety, tolerability and efficacy profile in migraine patients. Across all trials mAbs showed superior efficacy for the reduction of monthly migraine days compared to placebo with a net benefit of 2.8 days. Neither cardiovascular nor immunological safety concerns have emerged from clinical trials. Fremanezumab, galcanezumab, and erenumab are approved in the USA and Europe. Based on trial data there is no reason why these mAbs should not become first-line therapies in future. For now, we advocate for the use of mAbs in migraine prevention for patients who failed a minimum of two standard oral treatments based on the novelty and costs of this approach. mAbs are also effective in patients with medication overuse and with comorbid depression or anxiety disorders. Taken together, mAbs are likely to usher in a new era in migraine prevention and provide significant value to patients.

KEYWORDS:

• CGRP
• migraine
• clinical trial
• phase III
• placebo
• chronic migraine

Article highlights

• mAbs against CGRP and its canonical receptor are the first available migraine preventives directed against a specific target in migraine pathophysiology.

• In phase II and III trials, CGRP-(receptor) mAbs led to a significant reduction of MMD compared to placebo in both EM and CM with a rapid onset of action.

• CGRP-(receptor) mAbs demonstrated a good safety and tolerability profile. AEs were mostly mild to moderate in severity and similar to placebo in most trials.

• Patients with prior treatment failures and patients with medication overuse benefit from the preventive treatment with a CGRP-(receptor) mAb.

This box summarizes key points contained in the article.

Declaration of interest

B Raffaelli has received research funding from and honoraria for consulting from Novartis Pharma. L Neeb has received honoraria for consulting from Eli Lilly and Novartis Pharma, and for scientific presentations by Pharm Allergan, Desitin, Hormosan, Eli Lilly, Novartis Pharma, and TEVA. U Reuter has received honoraria for consulting from Amgen, Pharm Allergan, Autonomic Technologies, Co-Lucid, Eli Lilly, Medscape; StreaMedUp, Novartis Pharma and TEVA, and for scientific presentations by Amgen, Allergan, Eli Lilly, Co-Lucid, Medscape, Novartis Pharma, and TEVA. All authors are also involved as investigators in clinical trials with monoclonal antibodies from Amgen, Alder, Eli Lilly, Novartis, and TEVA without personal remuneration. The authors have no other relevant affiliations or financial involvement with any organization or entity with financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

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

Additional information

Funding

This paper was not funded.