CALCA and migraine disorder: Although anti-CGRP antibody therapies showed efficacy in patients, they areinadequate for the control of severe migraine in many patients and are ineffectivefor reducing osteoarthritis pain [59–61].Therefore, there is still a substantial unmet medical need of therapeutics that canbetter control CLR/RAMP-mediated pain response and tumor growth/angiogenesis.Because peptide antagonists have a volume of distribution ~3 times that of a typicalantibody, they have better access to target receptors at the nerve endings and thetumor microenvironment.