CGRP therapies are a new type of medication used to prevent and treat migraine attacks.
The CGRP breakthrough
CGRP stands for calcitonin gene-related peptide, and it is a protein that is released around the brain. When CGRP is released, it causes intense inflammation in the coverings of the brain (the meninges), and for most migraine patients, causes the pain of a migraine attack.
The new migraine medications work by blocking the CGRP. CGRP inhibitors are the first drugs developed for migraine prevention. All other agents used to prevent migraine prior to 2018, were originally developed for the management of other conditions and include antidepressants, blood pressure medications, antiseizure medications, antihistamines, and more.
CGRP migraine treatments work in one of two ways to prevent or treat migraine attack:
- They block the receptors in and around the brain where CGRP must attach to work. (Aimovig, Nurtec and others)
- They bind to CGRP ligand and prevent it from working. (Emgality, Ajovy, Vyepti and others)
By stopping the CGRP from working, it also stops most migraine attacks.
CGRP inhibitors have had a transformational impact on migraine management since their introduction in 2018, and have been considered first-line treatments since 2024. They are very effective and have few side effects.
A 2018 study found that almost a third of people tested had 50 percent fewer migraine attacks. Their migraine symptoms also lasted fewer days. In other research, a third of the people with migraine had up to 75 percent improvement. Similarly, Migraine Australia found in a survey of our members that 36% of people had a 75% or greater reduction in frequency and severity of migraine symptoms. CGRP treatments have also proven to be effective for people who did not have success with other medications.
CGRP medications currently available in Australia:
- erenumab (Aimovig)
- fremanezumab (Ajovy)
- galcanezumab (Emgality)
- eptinezumab (Vyepti)
- rimegepant (Nurtec)
All of these medications are designed to be used as preventatives to reduce the number of attacks, while Nurtec may be used as either a preventative and/or an abortive when attacks occur.
Who should consider CGRP therapy
CGRP medications may provide benefit for any patient with a confirmed diagnosis of migraine. The preventative medications are generally clinically indicated as suitable for anyone with more than 4 migraine affected days per month.
Migraine is not a headache. It is a complex genetic sensory processing disorder that can be very debilitating. To confirm a diagnosis of migraine, doctors should refer to the International Classification of Headache Disorders: note the most simple form of migraine without aura can only be diagnosed after at least five attacks involving a throbbing or pulsating headache on one side of the head, plus nausea/vomiting and/or sensitivity to light or noise. Headache alone with no other symptoms, no matter how frequent or intense, is likely to be better accounted for by another headache disorder, or another neurological condition.
Many people who have not had much benefit from other migraine treatments have done very well on CGRP therapy. This includes people with atypical migraine types that do not include headache, and rarer types of migraine like hemiplegic migraine (which causes stroke like symptoms) and vestibular migraine (which causes intense dizziness and vertigo). Read more about the types of migraine.
As yet, we don't have any way to know which of the new medications will work best for you. We know that people have a different response to the different medications, but we don't know why that is, so it really is a case of just pick one and try it!
Can I use CGRP therapies if I am pregnant or TTC?
Discuss the pros and cons with your doctor. The CGRPs have not been proven to be definitively safe to take during pregnancy, but they have not been found to be dangerous either. There are some concerns as these medications are still relatively new and CGRP plays an important role in pregnancy.
The CGRP treatments were tested on monkeys in clinical trials with no adverse effects noted. For this reason, the TGA has classified these medications as Pregnancy Category B1.
There have been no clinical trials of CGRP treatments in human pregnancies, but case reports and analysis of small numbers of patient records have found no significant issues, and rates of problems such as miscarriage are the same as those not taking the medication. Most drug companies are now keeping registers of pregnant women in an effort to work towards determining if they are safe to use in pregnancy, but most clinicians will advise you to stop using the longer acting monoclonal antibody injectables at least six months prior to trying to conceive. Nurtec takes much less time to leave your system, so can be taken for much longer, but has been found to pass through to breast milk so should not be started again until after you stop breastfeeding.
Read more about treatment options during pregnancy at the Association of Migraine Disorders.
The differences between CGRP medications
There are two types of CGRP inhibitors:
- CGRP monoclonal antibodies (MABs), which are used for migraine prevention:
- Erenumab (Aimovig)
- Fremanezumab (Ajovy)
- Galcanezumab (Emgality)
- Eptinezumab (Vyepti)
- CGRP receptor antagonists (gepants), which are used both as abortive and/or preventive migraine medications
- Rimegepant (Nurtec): Acute or preventive treatment of episodic migraine
- Atogepant (Aquipta): Preventive treatment - TGA approved but not yet available in Australia
- Ubrogepant (Ubrelvy): Acute treatment - not yet available in Australia
- Zavegepant (Zavzpret): Acute treatment - not yet available in Australia
Like most new medicines, accessing the CGRP treatments privately is expensive. Emgality, Ajovy, and Vyepti are the only ones currently available on the PBS. The specifics, restrictions and costs for each one are outlined below.
Aimovig
Type: MAB
Usage: Preventative
Dosage: 70mg or 140mg, self-administered autoinjector pen, every 4 weeks
Mechanism of action: blocks the CGRP receptor
Known side effects: allergic reactions, constipation, and high blood pressure
Cost
Aimovig is not currently available on the PBS.
Aimovig is available on a private prescription between $750 and $850 a month. All free trials have ended. A discount program enables you to get 140mg (2 x 70mg pens) for $695. To do this you need to:
1. Email your prescription to [email protected]
2. Order and pay for your Aimovig at http://aimovig.phusionpayments.com.au/ including nominating which pharmacy you will collect from.
3. Take the hard copy of your prescription to your pharmacy for dispensing.
Emgality
Type: MAB
Usage: Preventative
Dosage: 120mg, self-administered autoinjector pen, every month. On your first use you take an additional 'loading dose' of 120mg (240mg total for first use only).
Mechanism of action: blocks the CGRP ligand
Known side effects: allergic reactions which may cause difficulty breathing
Cost
Emgality is listed on the PBS. However, the vast majority of people will still only be able to access it via a private prescription.
Those who meet the following criteria will be able to get Emgality on the PBS.
- You must have Chronic Migraine (15 headache days, 8 of which are migraine days) for at least six months.
- You must have failed three older medications like propranolol, topiramate and amitriptyline
- You must be managed for medication overuse headache
- You must be under the care of a neurologist, or a GP in consultation with a neurologist
- You cannot get both Emgality and other CGRP's or Botox on the PBS.
If you qualify for Emgality on the PBS you must achieve a 50% reduction in migraine frequency and severity to continue to get it on the PBS after the first 6 months. You will be charged the maximum PBS co-pay rate of $31.60 or $7.70 with a concession card (as of 1st January 2024). As pharmacies are able to choose to provide a discount (for medicines priced between $31.60 and $48.10), and the amount of that discount, the price of medicines may depend on the pharmacy. READ MORE
You can also get Emgality on a private prescription from either a neurologist or a GP. There are no restrictions or limitations for private prescriptions, so no minimum number of "migraine days" or drugs you need to try first.
Your doctor will need to log on to the Lilly portal for doctors – https://mylilly.com.au/ – and print out a voucher for you to take to the pharmacist. Then the pharmacist will need to order it in for you (it generally won’t be in stock). The recommended retail price is $263 per month with the discount voucher. Without the discount voucher the price varies considerably but is around $600 a month.
Ajovy
Type: MAB
Usage: Preventative
Dosage: 225mg, self-administered autoinjector pen or syringe, every month OR 675mg every three months (quarterly dosing) equivalent to three pre-filled syringes or autoinjector given in a single sitting at three different injection sites
Mechanism of action: blocks the CGRP ligand
Known side effects: itchiness or a rash
Cost
Ajovy is listed on the PBS. However, the vast majority of people will still only be able to access it via a private prescription.
Those who meet the following criteria will be able to get Ajovy on the PBS.
- You must have Chronic Migraine or High Frequency Episodic Migraine (8 migraine days per month for at least six months).
- You must have failed three older medications like propanolol, topiramate and amitryptiline
- You must be managed for medication overuse headache
- You must be under the care of a neurologist or a GP in consultation with a neurologist
- You cannot get both Ajovy and other CGRP’s, or Botox on the PBS.
- To access the quarterly dose option requires scripts to be supplied as "Reg 49" (prev Reg 24) and may require additional authority.
If you qualify for Ajovy on the PBS you must achieve a 50% reduction in migraine frequency and severity to continue to get it on the PBS after the first 6 months. You will be charged the maximum PBS co-pay rate of $31.60 or $7.70 with a concession card (as of 1st January 2024). As pharmacies are able to choose to provide a discount (for medicines priced between $31.60 and $48.10), and the amount of that discount, the price of medicines may depend on the pharmacy. READ MORE
You can also get Ajovy on a private prescription from either a neurologist or a GP. There are no restrictions or limitations for private prescriptions, so no minimum number of "migraine days" or drugs you need to try first.
There is an access program for Ajovy called Momentum, where your pharmacy signs up and orders via Teva's portal. More information is available on the process here. This will allow you to purchase Ajovy for $299 per month instead of the normal rrp of $850 per month. Ask your pharmacist to call Teva Medical Information on 1800 288 382 if they are not already enrolled/have difficulty setting up and ordering from the portal, or to assist them with any other questions they have.
Vyepti
Type: MAB
Usage: Preventative
Dosage: 100mg or 300mg administered as a 30-minute IV infusion every 12 weeks
Mechanism of action: blocks the CGRP ligand
Known side effects: allergic reactions, or a stuffy nose
Cost
The 100mg dose of Vyepti is listed on the PBS, however as it requires infusion that has to be done in a clinic or hospital, any additional out-of pocket costs should be discussed with your doctor or neurologist. The 300mg dose is only available by private prescription.
Those who meet the following criteria will be able to get Vyepti on the PBS.
- You must have Chronic Migraine (15 headache days, 8 of which are migraine days) for at least six months.
- You must have failed three older medications like propanolol, topiramate and amitryptiline
- You must be managed for medication overuse headache
- You must be under the care of a neurologist or a GP in consultation with a neurologist
- You cannot get both Vyepti and another CGRP, or Botox on the PBS.
If you qualify for Vyepti on the PBS you must achieve a 50% reduction in migraine frequency and severity to continue to get it on the PBS after the first 6 months. You will be charged the maximum PBS co-pay rate of $31.60 or $7.70 with a concession card (as of 1st January 2024) for the medication, additional treatment costs may apply. READ MORE
You can also get Vyepti on a private prescription from either a neurologist or a GP. There are no restrictions or limitations for private prescriptions, so no minimum number of "migraine days" or drugs you need to try first. However the cost, at $1800 for 100mg and over $3000 for 300mg, is prohibitive for most. Discuss with your doctor.
Nurtec
Type: Gepant
Usage: Preventative or Abortive
Dosage: dissolving wafer form, and may be taken once per day during an attack, or every other day as a preventative
Mechanism of action: blocks the CGRP receptor
Known side effects: allergic reactions, nausea, indigestion or stomach pain
Cost
Unfortunately, Nurtec is not yet listed on the PBS, and is only available through private prescription (packs of 2 or 8). Either a neurologist or a GP is able to prescribe Nurtec.
While the price of Nurtec will vary depending on pharmacy it is expected to cost approximately $60 - $80 for a pack of two, or $250-$300 for a pack of eight wafers.
Released, but not yet available in Australia:
- atogepant (Aquipta in Australia, or Qulipta in the US) Abbvie has advised while the medication has been approved by the TGA, it will not be released into the Australian market at this time as it was not recommended for inclusion onto the PBS.
- ubrogepant (Ubrelvy, available in the US) - not yet approved by the TGA
- zavegepant (Zavzpret, available in the US) - not yet approved by the TGA
The gepants under development are mostly tablets, zavegepant is being developed as a nasal spray.
How do I get CGRP medications?
CGRP medications must be prescribed by a doctor. Most commonly that is a neurologist, pain specialist, or a GP in consultation with a specialist.
Once you get your prescription, your pharmacy will normally need to special order the medication in, as they are still new and not many pharmacists keep them in stock. Nurtec can be ordered online from some of the bigger pharmacy chains.
Aimovig, Ajovy and Emgality must be kept in the fridge until you are ready to use them. They are shipped from the drug companies to the pharmacy in refrigeration, and your pharmacist will keep it in the fridge. When they dispense it to you, they should put it in a bag that will help keep it cold or you may want to take an insulated bag, like a school lunch bag, to put it in for the journey home. Make sure you put it straight into your own fridge until you are ready to take it. Make sure you let it warm up to room temperature before you take it (otherwise it really stings!)
Vyepti is administered as an infusion (and IV drip), so your prescribing doctor will need to organise for that to happen at a clinic or hospital. There may be some out of pocket costs which you should ask about before confirming Vyepti is the right treatment for you.
The risks associated with CGRP therapies
All medications have side effects and risks. As they are still relatively new, all the effects of CGRP migraine treatments are not yet known. There may be some long-term risks that can happen in some people.
The most common CGRP migraine treatments have to be injected. This can cause pain. Additionally, an injection site on the skin can get infected. Washing your hands, cleaning the site, and using new needles each time is important. Additionally, we know:
- Aimovig may cause allergic reactions, constipation, and high blood pressure
- Emgality can cause allergic reactions, which may cause difficulty breathing
- Ajovy may cause itchiness or a rash
- Vyepti may cause allergic reactions, or a stuffy nose
- Nurtec may cause allergic reactions, nausea, indigestion or stomach pain
Many have noticed that their migraine pattern and symptoms change once starting a CGRP treatment. Weight gain and loss have also been reported anecdotally, as well as changes to periods and hair loss.
If you have anxiety or depression, as most people with migraine do, it is a good idea to work with your psychologist on adjusting your perspective when starting CGRP therapies. Because the response can be quite rapid, some people find their anxiety increased as they are still bracing for the next attack which doesn't come. Additionally, for many who had lost all hope of effective treatment, the anxiety of these new treatments possibly not working can be overwhelming. Give yourself permission to be well, and try not to over-think whether you are experiencing side effects or whether the medication is working or not.
You may also find that your triptan medications do not work as well as they used to. This is because the CGRP dilated the vessels in your brain, and the triptan would constrict them; with the CGRP being blocked the triptan doesn’t have as much impact.
CGRP plays a key role in dilating or widening your blood vessels. This helps to balance blood pressure. It is theorised that migraine medications that lower CGRP levels may cause side effects that affect your blood pressure and heart, but no research or clinical trial has recorded significant cardiovascular problems as yet. If you are on blood pressure or heart medications be sure to discuss this with your doctors before beginning CGRP treatment.
CGRP is also involved in other body mechanisms. For example, it helps with wound healing and plays a role in some of the digestive organs. It’s not yet known if blocking this chemical protein could affect wound healing or trigger digestive disorders. Some people may be more prone to getting head colds.
All of the CGRP monoclonal antibodies have been designed to not impact on the immune system. They just use the immune system for delivery. Your immunity is not suppressed, and you are not more vulnerable to bacteria or viruses, including COVID-19.
If you have comorbidities or other health concerns you may want to consider the side effects a little more closely, or ask in a Migraine Australia support group which one worked best for others with similar concerns.
Summary
CGRP migraine treatment is a new type of treatment. It may work better for some people with migraine than other kinds of medications.
CGRP migraine treatments give people relief by preventing migraine attacks from happening, and by reducing the length and severity of attacks. Side effects are generally mild.
Like any medication, CGRP treatment may not be right for you. Talk to your doctor to find out; they may recommend trying it for a few months.
Keep a migraine diary before starting a CGRP medication and for the first few months of taking it so you can measure how well it works for you. Let your doctor know of all changes in symptoms and any side effects you may have.