Calcitonin-gene-related peptide pathway mAbs and migraine prevention

Monoclonal antibodies (mAbs) targeting the calcitonin-gene-related peptide (CGRP) pathway have been developed for episodic and chronic migraine prevention, either through binding the CGRP ligand (eptinezumab, fremanezumab, galcanezumab) or the CGRP receptor (erenumab). We provide an update on published Phase 2 and Phase 3 trials, safety/tolerability data, pharmacokinetics and mechanism of action of these biologicals.

The efficacy data from Phase 2 trials are corroborated by those from published Phase 3 trials, with a multitude of publications expected in 2018. Review of safety data concluded there was no difference in total adverse events or main adverse events (including upper respiratory tract infection, nasopharyngitis, nausea, injection-site pain and back pain) between the mAbs and placebo injections except apparently for dizziness. The site of action of these mAbs is not fully elucidated but current insight is that their effect resides in the periphery; a contribution of central effect(s) can however not be excluded at present.

Although efficacy of all four drugs is modest over placebo in episodic and chronic migraine prevention and overall comparable with available oral preventive treatments, current tolerability and (short-term) safety data of this new treatment approach certainly promise a major step forward for migraine patients.