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Zavegepant: Innovations in Migraine Treatment

Apr 21, 2025

Spotlight on Migraine: Zavegepant Discussion

Introduction

  • Host: Association of Migraine Disorders
  • Episode featuring: Dr. Timothy Smith
  • Topic: Zavegepant, a new gepant class medication for migraine treatment
  • Sponsored by: Biohaven and Intel Pharmaceuticals

Background on Migraine Treatment Evolution

  • Ongoing 5 to 6-year cycle of new treatment approvals since 2018
  • Introduction of CGRP monoclonals and gepants
  • 7 new preventive and 11 new acute therapies recently entered the market
  • 9 potential molecular targets in development for future treatments

Overview of CGRP and Gepant Medications

  • CGRP monoclonal antibodies: 4 marketed for migraine prophylaxis
  • Gepants: 3 small molecule CGRP blockers
    • Rimegepant (Nurtec ODT): FDA approved for preventive use
    • Atogepant: Pending approval (as of September 2021)
    • Zavegepant: Currently under study

Focus on Gepants for Prophylaxis

  • Gepants are orally administered, blocking CGRP receptors
  • Potential to reach receptors not targeted by monoclonal antibodies
  • No significant liver enzyme abnormalities (unlike first-gen gepants)

Atogepant and Rimegepant

  • Atogepant:
    • Oral tablet (60 mg daily)
    • Expected market release: Q3 2021
    • Reported adverse events: nausea, fatigue, constipation, etc.
    • Benign drug interaction profile
  • Rimegepant:
    • Approved for abortive therapy and preventive dosing (75 mg every other day)
    • Positive topline results with reduced migraine days

Zavegepant Details

  • Third-generation CGRP receptor antagonist
  • Developed by Biohaven
  • Various delivery forms: nasal spray, injection, orally disintegrating tablet, oral soft gel capsule

Nasal Spray Formulation

  • For acute therapy, not preventive
  • Absorbed well across nasal membranes
  • Investigated for use in COVID-19 related respiratory distress
  • Phase trials show 10mg and 20mg doses superior to placebo

Oral Gel Caps

  • As a preventive option
  • Phase 1 identified 100 mg & 200 mg as optimal doses
  • Phase 2/3 trial underway with 3,000 subjects
  • Comparison across placebo, 100 mg, and 200 mg doses

Pharmacological Profile

  • Highly selective for CGRP receptors, potentially more than other medications
  • Low potential for drug interactions due to excretion profile
  • Bioavailability varies significantly with administration route

Questions & Considerations

  • Can acute gepants be used with zavegepant as a preventive?
  • Comparison to atogepant and rimegepant
  • Dosing regimen and side effects
  • Drug interaction potential remains to be fully understood

Conclusion

  • Ongoing studies and trials will provide more data on zavegepant's efficacy and safety
  • Potential for unique position in migraine treatment landscape

Additional Information

Full transcript