|Erenumab (AMG-334) is the first-in-class investigational monoclonal antibody targeting the calcitonin gene-related peptide receptor (CGRPR) . 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. AMG-334 (a fully human monoclonal) is being investigated for its potential to treat migraine headache.
Anti-CGRPR antagonistic monoclonals are being developed in place of non-peptide small molecule CGRPR antagonists as these have suffered from hepatotoxicity liability 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.