Focus on zavegepant: the first intranasal third-generation gepant

Migraine is the leading cause of years lived with disability in people under 50 and its burden is increased by calcitonin gene-related peptide (CGRP)-driven chronicity. Newly approved small molecules that antagonize the CGRP receptor, gepants, have advanced from the hepatotoxic first-generation telcagepant to third-generation intranasal zavegepant; during this process of drug development, rimegepant, ubrogepant and atogepant, which are orally administered, have been launched and approved for clinical use with no warning for hepatotoxicity. Real-world, long-term postmarketing data about the efficacy and safety of gepants are awaited. The aim of the present drug evaluation study was to provide an overview of the novel, third-generation intranasal zavegepant, encompassing its development and future perspectives. Plain language summary Migraine is the leading cause of years lived with disability in people under 50 and the frequent chronicity of the disease increases its global burden. Recent research prompted the discovery of novel modulators fundamentally involved in the pathogenesis and chronicity of migraine, such as calcitonin gene-related peptide (CGRP). This induced the development of new drugs able to antagonize the CGRP receptor, called gepants. The purpose of the present study was to offer a monograph on the novel, third-generation gepant, zavegepant. It is the first gepant to be administered via the intranasal route. Here, the authors report the available data on the efficacy and safety of zavegepant and investigate future perspectives.