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Synonyms: Aimovig® | AMG 334 | AMG-334 | erenumab-aooe
erenumab is an approved drug (FDA & EMA (2018))
Compound class:
Antibody
Comment: Erenumab (erenumab-aooe, AMG-334) is a first-in-class fully human monoclonal antibody targeting the calcitonin gene-related peptide receptor (CGRPR) [7] (and the first approved GPCR targeted monoclonal). Antibody production was initiated by immunising mice with polypeptides from the N-terminal extracellular domains of human CRLR and human RAMP1, which are subunits of the CGRPR protein complex. Erenumab is used clinically to prevent migraine headache. The selectivity of erenumab for the CGRPR vs. the AMY1 receptor has not been fully established.
Anti-CGRPR antagonistic monoclonals are being developed in place of non-peptide small molecule CGRPR antagonists as these have suffered from hepatotoxicity liability (although this has been largely overcome by using different chemotypes) when tested as migraine prophylactics. Antibodies have the positive attributes of being able to span the relatively large binding domain across the CGRPR complex to provide effective blockade, offer the potential for selectivity given the similarity with other receptors in the family, and exhibit a prolonged serum half-life which facilitates longer dosing intervals [1]. 
Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
| No information available. |
Summary of Clinical Use  |
| Erenumab received US FDA approval in May 2018 as a once-monthly injection as a preventative treament for migraine sufferers. One of the determining clinical trials leading to this marketing authorisation was the Phase 3 ARISE trial, NCT02483585, for which results were published in May 2018 [2]. Phase 2 trial results were published in [8] and reported a significant reduction in migraine episodes in the patient group receiving the highest erenumab dose (70mg; monthly subcutaneous administration) compared to the placebo control group. EMA approval was granted in August 2018 for the treament of patients who suffer 4 or more mirgaines/month. |
| Mechanism Of Action and Pharmacodynamic Effects |
| Calcitonin gene-related peptide (CGRP) is a neuropeptide involved in migraine pathophysiology [3-5]. Antagonism of CGRP's interaction with its cognate receptor CGRPR by small molecules proved that this was a valid pathway for migraine intervention. However, small molecule CGRPR antagonists showed considerable hepatotoxicity which precluded futher clinical development. More recently, anti-CGRPR antibodies with antagonist activity have entered clinical development pipelines as an alternative to small molecule antagonists. Erenumab is one such monoclonal. Anti-CGRP ligand antibodies are also in development to target this same migraine pathway (for example, galcanezumab, fremanezumab and ALD403) [6]. |
| Clinical Trials | |||||
| Clinical Trial ID | Title | Type | Source | Comment | References |
| NCT02483585 | Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) Compared to Placebo in Migraine Prevention | Phase 3 Interventional | Amgen | ||
| External links |
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For extended ADME data see the following: Electronic Medicines Compendium (eMC) Drugs.com European Medicines Agency (EMA) |
