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What are CGRPs?

CGRP stands for calcitonin-gene-related peptide. It is a protein that acts like a neurotransmitter (a chemical messenger) throughout the brain and body. CGRP is present in large numbers in the trigeminal system, the sensory nerves that supply the head and neck.

Researchers discovered CGRP is found in high levels in migraine sufferers during an attack, providing a new target for pharmaceutical drugs to focus on. To target CGRP, pharmaceutical researchers have developed monoclonal antibodies, a type of biologic therapy that targets and neutralizes either CGRP or its receptors. These new treatments are classified as CGRP antagonists or inhibitors.

These drugs work by blocking the action of CGRP by either binding with CGRP to prevent it from binding with the receptor. The other way CGRPs work is by attaching to the receptor itself to prevent CGRP from binding with the receptor.1,2

FDA approved CGRPs

Three CGRP treatments are approved by the U.S. Food & Drug Administration (FDA):

CGRPs being studied

Several others are in development. The anti-CGRP drugs currently in development are:

  • Eptinezumab (ALD403)
  • Ubrogepant
  • Atogepant
  • Rimegepant1,3,5

How effective are CGRP drugs?

CGRPs are groundbreaking new treatment options for people with migraine. And, CGRPs show promise in reducing the number of migraine days per month or the pain of migraine. Four of the CGRP drugs – erenumab, galcanezumab, fremanezumab, and eptinezumab – are preventive migraine drugs. This means these drugs are given to reduce the frequency and severity of episodic and chronic migraines. Ubrogepant is an acute migraine medication. This means it is given when a migraine attack occurs to stop the migraine and provide relief from migraine symptoms.4-9

It is important to note that the clinical trials for these drugs cannot be compared to each other because each trial was set up differently. No studies have compared the CGRP treatments to each other. Some of the findings from clinical trials include:

  • Erenumab showed a reduction of 6.6 fewer migraine days per month6
  • Galcanezumab showed at least a 50 percent reduction in migraine headache days compared to placebo7
  • Fremanezumab showed a reduction of 3.4 to 3.7 fewer migraine days per month8
  • Eptinezumab showed a reduction of 3.9 to 4.3 fewer migraine days per month9
  • Of patients taking ubrogepant for a migraine attack, 20.7 percent to 21.8 percent experienced freedom from pain two hours after their first dose5

How are CGRP treatments administered?

The different CGRP treatments are administered in various ways:

  • Erenumab and galcanezumab are given by subcutaneous (under the skin) injection monthly6-7
  • Fremanezumab is given by subcutaneous injection monthly or once every 3 months8
  • Eptinezumab is administered by intravenous (IV) infusion every 12 weeks9
  • Ubrogepant is an oral tablet given as an acute medication to treat a migraine attack5

What are common side effects of CGRP antagonist?

Each CGRP treatment will have its own unique safety profile. Early results seem to indicate that CGRPs have fewer or less severe side effects than other migraine drugs.

Common side effects of CGRP antagonists include:

  • Injection site pain (for those that are injected)
  • Upper respiratory tract infection
  • Runny/stuffy nose
  • Back, stomach, or joint pain
  • Urinary tract infection
  • Fatigue
  • Nausea and vomiting8,10-12
Written by: Emily Downward | Last Reviewed: November 2019
  1. Migraine: the CGRP story. Pharmaceutical Journal. Available at http://www.pharmaceutical-journal.com/news-and-analysis/features/targeting-the-cgrp-protein-could-lead-to-a-preventative-treatment-for-migraine/20201917.article. Accessed 5/10/18.
  2. Goadsby PJ, Edvinsson L & Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol 1990;28:183–187. doi: 10.1002/ana.410280213
  3. Drugs.com. CGRP inhibitors. Available at: Accessed 11/5/19.
  4. FDA Approves Aimovig (erenumab-aooe), a Novel Treatment Developed Specifically for Migraine Prevention. Amgen press release. Available at https://www.amgen.com/media/news-releases/2018/05/fda-approves-aimovig-erenumabaooe-a-novel-treatment-developed-specifically-for-migraine-prevention/. Accessed 5/17/18.
  5. Barber J. Higher dose of Allergan’s oral CGRP receptor antagonist ubrogepant hits main goals of Phase III acute migraine trial. First Word Pharma. Available at https://www.firstwordpharma.com/node/1560352. Accessed 5/10/18.
  6. Tepper S, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017;16:425-434.
  7. AAN 2018: Lilly’s Galcanezumab Significantly Reduced Monthly Migraine Headache Days in Patients with Migraine Who Previously Failed to Respond to Multiple Preventive Therapies. Eli Lilly. Press Release April 24, 2018. Available at https://investor.lilly.com/news-releases/news-release-details/aan-2018-lillys-galcanezumab-significantly-reduced-monthly. Accessed 5/10/18.
  8. Teva's Fremanezumab Meets all Primary & Secondary Endpoints Across Both Monthly and Quarterly Dosing Regimens in Phase III Study in Episodic Migraine Prevention [press release]. June 7, 2017. Available at http://www.tevapharm.com/news/teva_s_fremanezumab_meets_all_primary_secondary_endpoints_across_both_monthly_and_quarterly_dosing_regimens_in_phase_iii_study_in_episodic_migraine_prevention_06_17.aspx. Accessed 5/10/18.
  9. Alder BioPharmaceuticals Announces Positive Eptinezumab Phase 3 Results for Prevention of Frequent Episodic Migraine [press release]. June 27, 2017. Available at https://globenewswire.com/news-release/2017/06/27/1029420/0/en/Alder-BioPharmaceuticals-Announces-Positive-Eptinezumab-Phase-3-Results-for-Prevention-of-Frequent-Episodic-Migraine.html. Accessed 5/10/18.
  10. Medscape. Phase 3 STRIVE and ARISE Trials Show Efficacy, Safety for Erenumab in Migraine Prevention. Brauser D. Available at http://www.medscape.com/viewarticle/879161. Accessed 5/10/18.
  11. Dodick DW, Goadsby PJ, Spierings EL, et al. Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2014;13:885-892. Abstract
  12. Dodick DW, Goadsby PJ, Silberstein SD, et al; ALD403 study investigators. Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomised, double-blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol. 2014;13:1100-1107. Abstract