CGRP receptor antagonist

5 April 2024

CGRP Medications: Better for Men, or Women?

James Discoveries & Stats, Information, Medications 0

CGRP related medications for migraine are helping a lot of people. But if you’re going to try one, which medication should you start with? Does your sex make a difference?

Gepant drugs - a difference between women and men?

This is a question that is rarely asked or studied. That’s why a study review published in the medical journal Cephalalgia this year caught my attention. It was one of many studies on CGRP-related drugs – but in this case it was looking at the difference between men and women.

And in the case of one type of drugs, there was a difference – the “gepants” – that is, CGRP receptor inhibitors/antagonists. The specific drugs we’re talking about are:

ubrogepant (Ubrelvy)
rimegepant (Nurtec ODT)
zavegepant (Zavzpret)

Now, when these medications are used for acute migraine treatment – that is, when they’re taken to stop a migraine attack in progress – the evidence is positive. For women. However, for men, there is not yet enough evidence to show a clear benefit.

That doesn’t mean they won’t work for you – and maybe future studies will show a clearer benefit. But it could be that some of the CGRP medications simply work better in women.

It would be helpful to have further studies here, because if this difference stands up in further trials, it would be an easy way to pop certain types of medication higher on the list, because they’ll have a better chance of success, for you.

What about other CGRP medications? The meds for chronic migraine known as CGRP antibodies (the ones that end in “umab” – like fremanezumab or erenumab) seemed to work well for both sexes. Preventative CGRP medications also seemed to help both men and women, but the authors of the study would like to keep an eye out for differences in future studies.

Again, at this point this information shouldn’t stop you from trying CGRP medications. It may be information that can be added to the other info your doctor has in order to decide which to try first.

That being said, we look forward to future studies. Anytime we can make the path shorter to something that works to fight your migraine, we’re very interested.

It will also be very helpful in the future to find out why this is, so that we can better target migraine attacks.

To check out the study for yourself, click on Evaluation of outcomes of calcitonin gene-related peptide (CGRP)-targeting therapies for acute and preventive migraine treatment based on patient sex (pdf).

7 November 2019

Very Different “CGRP Drugs”

James Information, Medications 0

With our current obsession with the four magic letters, “CGRP”, and the CGRP related drugs that are now hitting the market, many people have not realized that there are two very different types of CGRP drugs out there. So here’s a quick description to get you up to speed.

What is “CGRP”?

CGRP (calcitonin gene-related peptide) refers to a peptide, a type of amino acid, that is naturally in your body. A lot of study is currently being done regarding the connection between CGRP and pain. It does seem to play a key role in the way your body responds to pain, inflammation, and migraine in particular. It may be that problems with CGRP function may cause you to become overly “sensitive”, leading to chronic migraine and other chronic pain conditions. However, we still have a lot to learn about how it works.

Blocking CGRP?

So if we somehow block CGRP, could we lessen the symptoms of migraine, or even stop migraine in its tracks? Well, that does seem to be the case with some people. We could either do this in a preventative way – that is, take a medication regularly to keep CGRP under control. Or perhaps we could use it to stop a migraine attack that has already started – that is, use it as an abortive. But how do we actually lower levels of CGRP?

CGRP Inhibitor

What if we could target CGRP itself? That’s the goal of the new preventative drugs that are hitting the market now. They’re called CGRP inhibiting monoclonal antibodies (mAbs). These include erenumab (Aimovig), galcanezumab (Emgality), fremanezumab (Ajovy), and eptinezumab. These are taken by injection either monthly or quarterly in order to lessen migraine attacks and symptoms. You’ll notice that these drugs use mAb in their names.

CGRP Receptor Antagonists

“Inhibitor” and “Antagonist” have a similar meaning, but you’ll notice that in this case the target is slightly different. Instead of targeting CGRP itself, we go for the CGRP receptor. These drugs work very quickly, but they’re not getting to the market as fast because they’re being carefully studied to make sure adverse reactions are minimal.

However, because they are “fast” they should make great abortives – something to take when the migraine attacks hit. These are the “gepant” drugs – such as ubrogepant and rimegepant. Also called a receptor “blocker”, the mechanism is complicated but you can think of it as another way to keep CGRP from functioning, hopefully lessening migraine symptoms during an attack.

And then…

There are several other types of migraine drugs on the way, each with a different way of attacking migraine. These include 5-HT1F agonists, and anti-PAC 1 drugs. We’ll try to talk more about these in the future. But the idea is to stop the migraine chain-reaction so that symptoms are lessened or stopped. Ideally, the closer we get to the “source” of migraine, the more we’ll be able to stop it altogether.

1 February 2019

CGRP Antagonists: Not for Everyone? Experts Weigh in…

James Medications 1

When it comes to the new migraine drugs, such as Aimovig, Ajovy and Emgality, we can say, “So far so good”. Positive clinical trials, minimal side effects – there is legitimate hope that this new class of drugs will help many migraine patients.

That being said, specialists and researchers are not without their concerns about CGRP antagonists. So let’s take a quick look at what some of those concerns are.

Why would anti-CGRP drugs be a problem, if they fight migraine? CGRP seems to play an important role in sending pain signals. Lessening migraine symptoms by inhibiting CGRP seems to be working well for many people.

But here’s the catch – CGRP is in your body for a reason. If we lower CGRP levels, what will that affect? Our knowledge is limited, but it seems that CGRP has a wide range of important functions in the body. And the trials done so far are fairly short-term. What will the long term results be?

As Dr. Lawrence Robbins points out, “We will have a better feel for the true risk in 10 years.” Yes, but meanwhile?

Here’s the big challenge. Which patients will most benefit from these new meds? No one wants to spend more than is necessary – what if a cheaper treatment works better? And what if some patients have a higher risk of problems from anti-CGRP treatment?

Headache specialist Dr. Andrew Hershey wrote:

With the ongoing development of 4 different antibodies targeting the CGRP pathway, it will be difficult to determine whether unique patient populations will have a response to a specific drug or whether one agent is superior to others. Furthermore, many patients will probably still have a response to standard multidisciplinary treatment that is less costly in patient and provider time and dollars.”
Promise and Pitfalls of Preventing Migraine With CGRP Inhibitors

As we’ve already discussed, the clinical trials up to this point haven’t brought any major issues to light. But there is good reason to continue trials, and watch for problems.

Based on the science we have to date, what are the experts concerned about? What types of risk, or what types of concerns are they expressing? Here are a few of the top ones to watch for over the next few years:

Cardiovascular concerns: CGRP plays an important role in the cardiovascular system. For example it is involved in the dilation of blood vessels. Could long term use contribute to cardiovascular problems? The trials generally haven’t included groups at high risk. This is probably the biggest one specialists are watching for, and some may be reluctant to prescribe CGRP antagonists to those already at high risk for hypertension.
“Antidrug Antibodies and Immunoallergic Hypersensitivity”: Without getting into the details, this means that a drug can have a long term effect of causing unwanted immune responses, and/or the drug may become less effective as time goes by.
Hormones: Could these drugs interrupt proper hormone function? Specialists are especially watching those with thyroid problems, and also growth in children and adolescents (these drugs are only approved for adults for now).
Gastrointestinal disturbances: Could anti-CGRP drugs have a bad effect on your gut? Doctors will be especially watching those who have recently had ulcers or who have irritable bowel syndrome.
Pregnancy: Or, trying to get pregnant. Could CGRP interfere with pregnancy?

Again, we don’t have all the answers yet. These are concerns based on what we know about CGRP in the body, but there simply isn’t enough evidence to know the effect that these new medications will have, particularly long term. Hopefully, these issues will be minimal – or, in many cases, non-existent.

Some doctors may consider prescribing anti-CGRP medication for a time, and then having patients take a “drug holiday” for a while. Some may be hesitant to prescribe the drugs to those with cardiovascular or gastrointestinal problems.

Consider the risks – but remember, at this point, the risks seem to be small for most of us, especially if we’re not taking these drugs long term, and if we’re not already in one of the high risk groups above.

The question is not whether or not you should get the best possible treatment. The question is – what is the best possible treatment for you? Some patients will still find other treatments and combination treatments to be far superior and far cheaper than the new anti-CGRP drugs. Others will be helped by medications like Emgality, who have not been helped by other meds in the past.

As Dr. Amy R. Tso and Dr. Peter J. Goadsby wrote in 2017

An important task will be to attempt to identify patients more likely to benefit so personalized therapy can begin to offset the cost of the treatments by minimizing the number of patients treated who have no useful response.
Anti-CGRP Monoclonal Antibodies: the Next Era of Migraine Prevention?

For a summary of some of the challenges and concerns when it comes to this new class of drugs, check out Promise and Pitfalls of Preventing Migraine With CGRP Inhibitors. For a longer and more technical article for specialists, with many questions that may need to be answered, go to At Stake: The Possible Long-Term Side Effects of CGRP Antagonists.

3 January 2019

New Migraine Meds in a New Year – and should I care?

James Highlights, Medications, News 1

Although I wouldn’t recommend that anyone pin all their hopes on the up-and-coming migraine medications, yes, there are some reasons why you should care about the new meds that are out, and the new ones we may see this year (and beyond).

So let’s take a quick look at what’s been happening:

Over the past few months, three medications have hit the market. All three are CGRP inhibitors, a new class of targeted migraine medication.

Aimovig (erenumab) – self-injections once a month as a migraine preventative.
Ajovy (fremanezumab) – self-injections either monthly or quarterly for migraine prevention. May also be useful for episodic cluster headache.
Emgality (galcanezumab) – self-injections monthly. Has shown promise for both chronic and episodic migraine.

Yes, although all the same “class” of medication, each of these is different, with advantages and disadvantages. One may work where another may not. Readers may especially notice from the above list that Ajovy can be taken quarterly instead of monthly – that’s 8 few injections a year.

So what can we expect next from this class of medications? Here are three more that should hit the market in the months ahead:

Ubrogepant – this one is an oral abortive – swallowed when needed to stop a migraine attack.
Eptinezumab – self-injection, quarterly. Showing promise for chronic and episodic migraine. Already being promoted as a very “fast acting” option.
Rimegepant – oral medication, used either as an abortive or a preventative.

A lot of the differences between these medications aren’t listed above – and some will vary from patient to patient. However, notice that now we have more oral options, and more abortives (taken when the attack hits). So those who hate injections (even though injection technology is improving quickly, and is not as bad as it once was) have hope.

What else does this mean, besides the fact that one may work and one may not for you?

A lot of people are speculating what this will mean for price. At the moment, each of these are similarly priced. However, at the very least, it’s important to be aware of the special programs each of company will put in place, and how they will change. Especially early on, these companies will want to gain customers. There are ways to save money.

Also, these companies will want to promote what they see as benefits of their particular brand – so watch for that. Also, many are trying to gain customer loyalty by providing other services, such as helpful info or apps for your phone. Watch for that as well.

As we’ve talked about before, even as new anti-CGRP meds flood the market, a whole new class beyond that is being developed. Though not expected anytime soon, watch for news about:

ALD1910 – being developed by Alder Pharmaceuticals (developers of eptinezumab) as a migraine preventative.
AMG 301 – being developed by Amgen/Novartis (makers of Aimovig) as a migraine preventative.

For another perspective on the class of migraine drugs currently hitting the market, see A Crowded Field for Migraine Therapies, Where Recently There Were None.

3 October 2018

Ajovy for Migraine – and Cluster? Another New Drug

James Medications, News 0

Ajovy (fremanezumab-vfrm) (formerly called TEV-48125), a new anti-CGRP drug for migraine, was approved in the USA by the FDA last month.

Like Aimovig, Ajovy is taken by injection. It can be taken monthly, but unlike Aimovig it was also approved to be taken quarterly. A study that we talked about back in January showed that Ajovy was only slightly more effective when taken monthly. For many people, an injection every three months sounds a lot better than every month!

AJOVY You can read more about the history of this drug, along with more useful information, in the press release from Teva: Teva Announces U.S. Approval of AJOVY™ (fremanezumab-vfrm) Injection, the First and Only Anti-CGRP Treatment with Both Quarterly and Monthly Dosing for the Preventive Treatment of Migraine in Adults

So what about cluster headache? Though not yet approved for cluster, there are some signs that Ajovy and/or future anti-CGRP drugs may help a lot of cluster patients. If you’re interested in the technical details about the link between CGRP and cluster, check out For Your Patients-Cluster Headache: CGRP Implicated in Cluster Headache Attacks at Neurology Today.

Teva decided to scrap its trial of Ajovy for chronic cluster, when it didn’t look like the results would be as good as hoped. They do have high hopes for treatment of episodic cluster.

But even if Ajovy doesn’t turn out to be the best option for cluster patients, it does look very hopeful that one of the other CGRP related drugs may help bring significant relief.

Meanwhile, Ajovy is full-steam-ahead for migraine patients. For more information, visit the official Ajovy website here.