Anti-CGRP monoclonal antibodies for prevention of migraine

K K Jain MD (Dr. Jain is a consultant in neurology and has no relevant financial relationships to disclose.)
Originally released March 26, 2018; last updated March 24, 2020; expires March 24, 2023

Key points

 

• Monoclonal antibodies (MAbs) for migraine prophylaxis target calcitonin gene-related peptide (CGRP) receptor.

 

• The rationale for this approach is based on the role of CGRP in the pathogenesis of migraine.

 

• Three of the 4 MAbs in development (eptinezumab, fremanezumab, and galcanezumab) target CGRP itself, whereas the fourth, erenumab, targets CGRP receptor.

 

• Clinical trials have shown the efficacy and safety of anti-CGRP MAbs in reducing migraine attacks.

 

• Erenumab (Aimovig) and galcanezumab were approved in 2018. Eptinezumab and fremanezumab were approved by the FDA in 2020 (Spindler and Ryan 2020).

Historical note and terminology

Most preventive treatments for migraine are nonspecific, and their efficacy and safety are often unsatisfactory. Some monoclonal antibodies (MAbs), which target calcitonin gene-related peptide (CGRP) receptor or CGRP itself, are in development for migraine prophylaxis. CGRP is a neuropeptide that, along with its receptor, is found in both central and peripheral neurons and influences both neuronal modulation of pain as well as vascular activity (Edvinsson 2017; Iyengar et al 2017).

CGRP receptor (CGRP-R) is also a target for drugs for acute migraine attacks. Gepants, another CGRP-R antagonist class, are a new nonvasoconstrictive approach in the acute treatment of migraine. When compared with triptans, gepants show a similar efficacy profile. However, results of clinical trials of gepants have not been encouraging for their use in clinical practice. Some were discontinued during development due to concerns for hepatotoxicity or for unknown reasons. Clinical trials of other gepants for acute migraine continue but will not be discussed in this article.

Four anti-GRCP MAbs are in clinical trials and will be described in this article. The focus of this article will be on erenumab, the most advanced of these, which was the first to be approved.

 

• ErenumabIt was approved by the U.S. Food and Drug Administration and the European Medicines Agency in Europe in 2018.

 

• Eptinezumab

 

• Fremanezumab

 

• Galcanezumab

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