The neuropeptide CGRP acts on two receptor types. Drug design around CGRP can mean the trigeminal pain system is targeted fairly specifically, with apparently few side effects. Drugs being developed around CGRP include receptor blockers, and monoclonal antibodies against the peptide itself and the CGRP receptor.6,23

CGRP receptor antagonists are on the cusp of entering the market for treating migraine. Early hopefuls were olcegepant, which was dropped due to formulation problems, and telgecepant which was affected by liver enzyme issues.

Overcoming these issues, rimegepant, an orally-available, selective small molecule CGRP receptor antagonist, has undergone phase III trials in the US. The Food and Drug Administration is already considering an application for another CGRP antagonist, ubrogepant, with a decision expected late in 2019.24,25

Four CGRP antibodies have launched or are approaching market authorisation. Erenumab is an antibody to one of the known CGRP receptors (the calcitonin-like receptor/ receptor activity modulating protein CLR/RAMP1 complex). Galcanezumab, eptinezumab and fremanezumab are CRGP peptide antibodies.6