Evaluating rimegepant for the treatment of migraine

ABSTRACT

IntroductionCalcitonin gene-related peptide (CGRP) is a vasodilatory neuropeptide involved in the pathophysiology of migraine, a highly disabling neurovascular disorder characterized by severe headache attacks. Rimegepant is a small-molecule CGRP receptor antagonist approved by the FDA for acute treatment of migraine and currently under investigation for migraine prophylaxis. Areas covered The authors summarize available data on safety and tolerability of rimegepant and provide insights on its use for acute migraine treatment. Expert opinion Rimegepant seems to be well tolerated and superior to placebo for two-hour pain freedom. Moreover, rimegepant does not induce vasoconstriction, and is therefore not contraindicated in patients with cardiovascular disease, nor does it seem to induce medication-overuse headache. However, the therapeutic gain of rimegepant is only small, and since CGRP is a vital rescue molecule during ischemia, blocking the CGRP pathway might be detrimental. Although current evidence on CGRP receptor blockade has shown no cardiovascular adverse events, clinicians should remain critical about the use of rimegepant, as well as other CGRP (receptor)-inhibiting drugs. Further research should focus on determining the consequences of long-term CGRP blockade, especially during ischemia or cardiovascular disease, the exact receptors antagonized by rimegepant, and potential effects of combining rimegepant with other antimigraine treatments.

KEYWORDS:

• BMS-927,711
• CGRP
• gepants
• migraine
• rimegepant

Declaration of interest

A. MaassenVanDenBrink has received research grants, served as a consultant and has received speaker’s fees from Allergan, AbbVie, Amgen, Novartis, Eli Lilly and Company and Teva Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

One referee is an investigator for and has received research support from Biohaven and AbbVie. Another referee has served as a consultant and speaker for Eli Lilly and Company, Novartis, Teva Pharmaceuticals, and Grunenthal. Peer reviewers in this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

The authors are supported by a VICI grant (grant no. 9150181910040) from the Dutch Research Council.