Anti-CGRP monoclonal antibodies in migraine: current perspectives

Migraine is a highly disabling neurological pain
disorder in which management is frequently problematic.
Most abortive and preventative treatments employed are
classically non-specific, and their efficacy and safety and
tolerability are often unsatisfactory. Mechanism-based
therapies are, therefore, needed. Calcitonin gene-related
peptide (CGRP) is recognized as crucial in the pathophysiology
of migraine, and new compounds that target the
peptide have been increasingly explored in recent years.
First tested were CGRP receptor antagonists; they proved
effective in acute migraine treatment in several trials, but
were discontinued due to liver toxicity in long-term
administration. Monoclonal antibodies against CGRP
(LY2951742, ALD-403, and LBR-101/TEV-48125) or its
receptor (AMG334) were subsequently developed. As
reviewed in this study, numerous phase 1 and 2 trials and
preliminary results of phase 3 trials have shown a good safety/tolerability profile and efficacy in migraine prevention,
especially in high frequent episodic and chronic
forms. Being macromolecules, these mAbs are not suitable
for oral administration; however, their intravenous or
subcutaneous delivery can be performed at relatively low
frequency—every month or even quarterly—which
enhances patients’ compliance. Although not all migraineurs
respond to this treatment, and longer administration
periods will be needed to assess long-term effects, the
results so far obtained are extraordinarily promising. The
future introduction of mAbs on the market will probably
represent a turning point for prevention similar to that
represented by triptans for abortive treatment in migraine.