The Holy Grail of Migraine Medications? (2/3) - CGPR Blockers

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2018 is an exciting year for people who have migraines. In this three-part series, we will help you to understand the CGRP drug class better. On the previous blog article, we looked at an overview of the CGRP blockers. Today we will look at the unknowns of the CGRP drug class.

The first calcitonin-gene receptor peptide (CGRP) drug for treating migraines has been approved by the FDA this year with the introduction of Aimovig™ by Amgen and Novartis and more recently, two additional CGRP drugs  Ajovy™ by Teva and Emgality™ by Eli Lilly have been approved. There are currently two other CGRP drugs undergoing the drug approval process. The CGRP drug class offers a new way to treat migraines by using immunotherapy to specifically target the CGRP receptors. Many doctors and experts are excited with the CGRP drug’s potential to become a significant advancement in the migraine armamentarium with its high efficacy and low side effect profiles observed in the clinical trials. Although this new class of drug is promising, there are still many unanswered questions and unknowns regarding CGRP drugs.

Unknown Long Term Data

The biggest unknown is the long-term safety and efficacy of the drug, as no long-term data currently exists. CGRP is involved and affects many different physiologic systems including the cardiovascular system, gastrointestinal system, pituitary system, and the immune system. The short-term safety data has shown predominantly mild and low adverse effects but there is limited data on how long term effects of interfering with CGRP will affect the many different physiologic systems CGRP is involved in. Some potential long-term adverse effects could be increased risk of heart attacks and stroke from the loss of the protective cardiovascular role CGRP has on the cardiovascular system, decreased wound-healing abilities, and increased risk for ulcers and inflammatory bowel disease from the thinning of the mucosal lining of the gut.

Developing Antibodies To The Drug

The new CGRP drugs on the market are monoclonal antibodies, which uses the body’s immune system to target specific receptors in the body. The disadvantage of using antibodies is the risk of the body developing antibodies to neutralize the drug. When the body develops anti-drug antibodies, the efficacy and bioavailability of the drug can become greatly reduced and eventually render the drug ineffective. The body can also develop hypersensitivity reactions to the drug as body can think the antibody is a foreign agent and mount an immune attack on the drug.

Unknowns Within Drug Site Of Action

Although scientists have a general idea of how the CGRP drug works, there is still incomplete information on exact site of action of the CGRP drugs and other sites of action the CGRP can potentially affect. Other potential questions that remain to be answered are determining which migraine patients will respond the best with this drug and who will have minimal response to the drug, what the duration of the treatment should be, and what drug combinations can used with the new drug.

As with any newly approved medications that comes onto the market, there are many unknowns and unanswered questions that can only be answered with once a greater number of people use the drug and for a longer time.


1. Deen M, Correnti E, Kamm K, et al. Blocking CGRP in migraine patients – a review of pros and cons. J Headache Pain. 2017;18:96. doi: 10.1186/s10194-017-0807-1.

2. Villalon CM, Olesen J. The role of CGRP in the pathophysiology of migraine and efficacy of CGRP receptor antagonists as acute antimigraine drugs. Pharmacol Therapeut. 2009;124:309-323.

3. Dodick DW, Ashina M, Brandes JL, et al. ARISE: A phase 3 randomized trial of erenumab for episodic migraine. Cephalagia. 2018;38(6):1026-1037.

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