Gepants: targeting the CGRP pathway for migraine relief

Area of Science:

• Neurology
• Pharmacology

Background:

• Calcitonin gene-related peptide (CGRP) receptor antagonists (gepants) are emerging therapies for acute and preventive migraine management.
• New agents like atogepant, ubrogepant, rimegepant, and zavegepant expand therapeutic choices beyond triptans and monoclonal antibodies.

Purpose of the Study:

• To critically evaluate the pharmacology, clinical efficacy, safety, and therapeutic positioning of approved gepants for migraine.
• To summarize current evidence on gepant utilization in migraine treatment and prevention.

Main Methods:

• A comprehensive literature search was conducted across major databases (PubMed/MEDLINE, Embase, Web of Science, Scopus, Cochrane Library, ClinicalTrials.gov) from 1998 to September 2025.
• Included peer-reviewed clinical studies on gepant pharmacology, efficacy, and safety; excluded case reports, abstracts, and non-English articles.

Main Results:

• Four gepants are approved: atogepant for prevention; ubrogepant and zavegepant for acute treatment; rimegepant for both.
• Gepants demonstrate favorable pharmacokinetics, rapid onset, and convenient dosing (oral/intranasal).
• Clinical trials show significant reductions in monthly migraine days (prevention) and high rates of 2-hour pain freedom (acute treatment) compared to placebo, with generally benign safety profiles.

Conclusions:

• Gepants are a significant advancement in migraine therapy, offering effective and well-tolerated acute and preventive options.
• They are particularly valuable for patients with contraindications to triptans or cardiovascular risk factors.
• Further research will elucidate long-term safety and real-world effectiveness.