Anti-CGRP monoclonal antibodies in migraine: current perspectives

Abstract

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.

Migraine, Neurogenic Inflammation, Drug Development - Pharmacochemical Aspects

“…Three anti-CGRP and one anti-CGRP receptor mAb are under development. LYD2951742 (Arteaus Therapeutics, USA, Eli Lilly and Co., USA) has been proven to have better outcome than placebo in phase II clinical studies and three phase III studies are underway [73,74]. ALD 403 (Alder Biopharmaceuticals, USA) has shown promising results in a phase II trial [75].…”

“…ALD 403 (Alder Biopharmaceuticals, USA) has shown promising results in a phase II trial [75]. The ongoing phase III trial is planned to be completed in June 2017 [74]. LBR101/TEV-48125 (Labys Biologics, Pfizer, USATeva Pharmaceuticals, USA) has been proven to be efficient in migraine prevention [76] and an ongoing phase III clinical trial will be completed by October 2017 [74].…”

“…The ongoing phase III trial is planned to be completed in June 2017 [74]. LBR101/TEV-48125 (Labys Biologics, Pfizer, USATeva Pharmaceuticals, USA) has been proven to be efficient in migraine prevention [76] and an ongoing phase III clinical trial will be completed by October 2017 [74]. AMG 334 (Amgen, USA-Novartis) is the only mAb that targets the CGRP receptors [77].…”

Acute treatment of migraine: quo vadis?

“…The scenario revolving around migraine is populated today by various actors: the new pharmacological class of monoclonal antibodies, subcutaneous or intravenous, for CGRP (CGRP MoAbs) or its receptor (CGRPr MoAbs), and the small-molecule oral CGRPr antagonists [2,3].…”

“…Facing this enormous social impact, only onabotulinumtoxinA has been evaluated, on serendipity basis, as effective chronic migraine preventative treatment [1]. Pharmacological research is now moving important steps forward towards bridging the 30-year gap of new preventative class drugs for migraine, with a new molecule in its final phase of development: monoclonal antibodies for calcitonin gene-related peptide (CGRP) or its receptors (CGRPr) [2,3].…”