Calcitonin gene-related peptide receptor as a novel target for the management of people with episodic migraine: current evidence and safety profile of erenumab

Abstract

Maria Adele Giamberardino,1,* Giannapia Affaitati,1,* Raffaele Costantini,2 Francesco Cipollone,3,* Paolo Martelletti4,* 1Department of Medicine and Science of Aging, Headache Center, Geriatrics Clinic and Ce.S.I.-Met, “G. D’Annunzio” University of Chieti, Chieti, Italy; 2Department of Medical, Oral and Biotechnological Sciences, Institute of Surgical Pathology, “G. D’Annunzio” University of Chieti, Chieti, Italy; 3Department of Medicine and Science of Aging, Medical Clinic and Ce.S.I.-Met, “G. D’Annunzio” University of Chieti, Chieti, Italy; 4Department of Clinical and Molecular Medicine, Regional Referral Headache Center, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy *These authors contributed equally to this work Abstract: Migraine is a highly disabling neurological condition, and preventative treatment still remains problematic, due to aspecificity of the majority of the currently available prophylactic drugs. Calcitonin-gene-related peptide (CGRP) plays a crucial role in migraine pathophysiology; agents aimed at blocking its activity have, therefore, been developed in recent years, among which are monoclonal antibodies (mAbs) against CGRP, to prevent migraine. Erenumab is the only mAb that targets the CGRP receptor instead of the ligand, with high specificity and affinity of binding. This review will report on the most recent data on erenumab characteristics and on the results of clinical trials on its employment in the prevention of episodic migraine (4–14 monthly migraine days): one Phase II and two Phase III trials (completed) and one Phase III trial (ongoing). Monthly subcutaneous administration (70 mg or 140 mg) of erenumab vs placebo for 3–6 months showed significantly higher efficacy in reducing the mean monthly number of migraine days and the use of migraine-specific medication, and in decreasing physical impairment and impact of migraine on everyday activities (P<0.001). A favorable safety profile was demonstrated by the lack of significant differences in the occurrence of adverse events in erenumab-treated vs placebo-treated patients. Global results so far obtained point to erenumab as a new promising candidate for the preventative treatment of episodic migraine. Licence applications for erenumab were recently submitted to the Food and Drug Administration in the USA and European Medicines Agency in Europe (May/June 2017). Keywords: erenumab, episodic migraine, CGRP, CGRP receptor