What are CGRPs, and Why Should I Be Excited?

A new medication treatment for migraine sufferers is starting to make big waves.

Migraine sufferers have been searching far and wide for both medication and complementary treatments for their pain. Since different treatments affect different people in different ways, there is no tried-and-true method for ending chronic migraine. A single person, for example, may try anti-depressants followed up by cold packs, acupuncture, or neurostimulation just to achieve pain relief—and that relief may not be achieved each time a migraine attacks. However, a new preventive medication in the pipeline—called a CGRP—is about to make a big impact on migraine treatment.

If you haven’t yet heard of a CGRP, which stands for calcitonin gene-related peptide, you’re not alone. A national survey on Migraine in America 2018 found that only one-third of approximately 4,350 respondents are aware of the new therapy. Respondents were very intrigued about the new medication (79% said they were “very likely” to use them) but were unsure about how they could integrate them into their existing treatment plan.

Clinicians, too, are still learning about this new class of medications, leading to a lot of questions asked by both parties. This brief primer should help to fill in some of the gaps about this new treatment for those suffering from chronic migraine.

What is a CGRP?

Calcitonin gene-related peptides (CGRPs) are present in many organs throughout the human body, including the brain, and they play multiple roles depending on their target. When released around the nerves of the head that are most associated with migraine, for example, CGRPs causes blood vessels to expand and can bring about inflammation. In combination, this effect can cause the type of pain typically experienced with a migraine.

CGRP-targeting medications, clinically referred to as CGRP receptor antagonists or CGRP antibodies, have been shown to either block the peptide itself or its receptor structures through which it acts, thereby preventing a migraine attack.

Aimovig, the first FDA-approved CGRP antibody indicated to prevent migraine in adults, can be administered once a month via a single-use autoinjector (ie, self-injection). Additional CGRPs on the market also offer monthly injections (Emgality and Ajovy) as well as quarterly (Ajovy) injectable options.  A few oral medications are being developed for acute and episodic treatment of migraine as well.

Of note, this new class of CGRP antibody medications is only indicated for adults, age 18 and up, to date.

What's Available Now

  • erenumab-aooe (Aimovig, Amgen/Novartis, administered monthly at-home via subcutaneous injection). FDA approved in May 2018 as the first US-approved CGRP inhibitor for adult migraine prevention)
  • eptinezumab (Vyepti, administered quarterly via intravenous infusion). FDA approved in February 2020 as the first IV formulation for the prevention of migraine in adults and is expected to be available on market in April 2020; recommended dose is 100 mg every 3 months. 
  • fremanezumab (Ajovy, administered monthly or quarterly via subcutaneous injection). FDA approved in September 2018.
  • galcanezumab (Emgality, administered monthly via subcutaneous injection). FDA approved in September 2018 for preventive migraine and in June 2019 for episidoic cluster headache.
  • ubrogepant (Ubrelvy, administered orally). FDA approved for acute migraine treatment in December 2019 as the first oral CGRP for migraine with or without aura.
  • rimegepant (Nurtec ODT). FDA approved in February 2020 for abortive use in migraine sufferrers as the first fast-acting orally disintegrating tablet in the CGRP class.
  • lasmiditan (Reyvow) is also a new abortive tablet for migraine with or without aura, approved by FDA in October 2019.
  • others are in the works with injection, IV, and oral delivery method options.


What’s the Big Deal?

Why should migraine sufferers be excited? CGRPs are the first drugs to specifically target migraine, as opposed to previous “migraine” medications that were actually formulated to treat other conditions, such as high blood pressure or depression. The CGRP class offers a preventive option for patients that has, in some trials, also prevented a migraine’s commonly associated side effects, such as light, sound, odor sensitivity, and nausea, from occurring.

According to the American Migraine Foundation, these groundbreaking medications have decreased the frequency of migraine in many patients by at least 50% (for up to one-third of patients, headaches improved by 75% or more), and in some, about 1 in 6 patients, the migraines seemed to go completely away, at least for 3 months or longer. In trials, many patients saw their migraine days decrease by 2 to 5 per month. For some other patients, they have not been helpful. If successful, CGRPs may also be useful to those with cluster headache or post-traumatic headache as well.

What are the risks or side effects?

While many CGRP studies to date have shown minimal, short-term side effects and passed Phase 3 safety/efficacy trials, many questions around long-term risks, as well as potential interactions of CGRP antibodies with other medications and/or conditions, are still being addressed. It will take several years, and several hundred thousand patients, to truly assess this side effect profile. This is the case when any new class of medication enters the market, but caution is still warranted and it’s best to speak to your doctor about whether CGRPs are right for you. Pain relief from these medications has been shown to differ between patients, and individuals with certain other diagnoses, such as cardiovascular conditions, may be at a higher risk. It is also important to note that CGRPs were not tested in pregnant women.

Natalie Murinova, MD, director of the University of Washington’s Neurology Headache Clinic in Seattle, advises that patients considering this new medication continue with any alternative therapies they may be using to field off migraine attacks. For example, keeping stress levels under control, limiting acute medications, and maintaining an exercise program are still beneficial to continue.

The CGRP antibody may help decrease migraine activation before it begins, but it does not decrease the cause of the activation in the first place, Dr. Murinova explained to PPM. (This is one reason why it is indicated to prevent an attack, not to stop the symptoms after an attack begins). Therefore, it is beneficial to continue to work on decreasing your known migraine triggers and talk to your primary care or headache specialist about whether these medications will be right for you.

Women experiencing migraine reliefThe new CGRP migraine prevention class may offer relief for millions. (Source:123RF)



How much do they cost?

The US list price of these drugs varies between $300 and $575 monthly. If your insurance covers it, these companies have copay cards to bring the cost down close to zero. The AImovig Ally product support program from manufacturer Amgen/Novartis, and similar ones from Teva and Lilly, are meant to help patients navigate insurance coverage and identify potential access resources for those who are uninsured or underinsured.

The future is certainly looking bright for migraine sufferers seeking a way to prevent their migraine attacks. While more studies need to be done on the long-term potential benefits of CGRPs, as well as the side effects, the immediate results are promising. As more companies obtain regulatory approval for their CGRP-antibodies, and this new wave of treatment begins to make its way into practice, a new fixture in your treatment plan is possible. 


(Updated March 2020)

Updated on: 07/17/20
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