Fighting to put more tools in the migraine tool box

Migraine Australia members voted for our priorities for 2021-2022 to be around improving medication access. We're going to do that, and we're not just limiting it to the new drugs in the pipeline. 

In addition to all the new migraine drugs coming to market thanks in large part to the CGRP breakthrough, there's a number of older drugs that never came to Australia for which we are going to actively seek to find willing suppliers. 

Some of these medications you will have heard of, and some you won't. So we thought we'd take a moment to explain what all the drugs were and what we want for each of them. Our wish list is still expanding, if there is a migraine medication you wished you could get that's not on this list, please email RK and let her know about it. 

IMPORTANT: The following information is not medical advice. All of these medications have side effects and may not be right for you. Discuss your individual care plan with your doctors. 

CGRP mAbs

Obviously, most of the focus and excitement will continue to be on the CGRP antagonist monoclonal antibody medications for some time. You can read more about the CGRP antagonist medications here including how to access them.

CGRP antagonist medications work by blocking Calcitonin Gene Related Peptide - or CGRP - which has been proven to surge during migraine attack. Some medications work by targeting the CGRP ligand (Emgality, Ajovy, Vyepti), others target the CGRP receptor (Aimovig and the Gepants). 

EMGALITY (galcanezumab)

STATUS: Approved by TGA. On PBS for a very limited criteria of people, available through a discount program for others. 
NEED: Expansion of PBS criteria to all people who need preventative medication

Emgality is a monoclonal antibody that works by binding to the CGRP ligand, making it ineffective as the receptors can't see it. It was the first CGRP medication to be listed on the PBS, but the limitations are intense. You need to be under the care of a neurologist, have chronic migraine (15+ headache days, 8 of which are migraine days) for at least three months, have failed three older medications (usually propanolol, topiramate and amitryptiline), not have medication overuse headache, you can't get both Botox and Emgality on the PBS, and you need to demonstrate a 50% reduction in headache days by 6 months to continue to get it. 

Migraine Australia will keep advocating for all the CGRP medications to be available for appropriate patient groups, without these artificial limitations that are solely about limiting cost. 

In the meantime, the drug company Lilly will continue to provide Emgality direct to patients under their Ember program, which allows discounted access to the medication for $263 a month (it was originally close to $1000). Note: you can get access to the Ember program through your GP, you don't need to see a neuro. 

AJOVY (fremanezumab)

STATUS: Approved by TGA. On PBS for a very limited criteria of people as of 1 August, available through a discount program for others. 
NEED: Expansion of PBS criteria to all people who need preventative medication

Ajovy is another monoclonal antibody and works similarly to Emgality, but can be taken either monthly or quarterly. Ajovy has just been listed on the PBS with the same restrictions as Emgality, and you won't be able to get it as a quarterly dose, only monthly. 

Ajovy is also available at the discounted price of $287 per dose through their Momentum program (discounted from $850). 

VYEPTI (eptinezumab)

STATUS: Approved by TGA. Not yet available.
NEED: PBS listing

The newest entrant for the Australian market, Vyepti is really exciting for lots of reasons. It works similarly to Emgality and Ajovy, but is delivered as a quarterly infusion (that is through an IV drip). It has a really fast uptake, with some people having complete relief from even really intense migraine attacks within hours... which means it also has a role to play in the emergency setting, putting another tool in the tool box for emergency doctors managing people in migraine crisis. 

There are some extra logistical issues in making Vyepti available because you need a place and staff to deliver the 30-minute infusion. Lundbeck are working on those issues now, and we expect it will become available under a similar discount program late in 2021. The PBS application for Vyepti has not yet begun, but we expect it will be a bit of a fight. 

AIMOVIG (erenumab)

STATUS: Approved by TGA. Available privately, withdrawn from PBS consideration.
NEED: PBS listing

Aimovig was the first of the CGRP medications and has a different mechanism of action to all the others. Unfortunately, it was given a really tough time by PBAC - the Pharmaceutical Benefits Advisory Committee that has to approve all new drugs for the PBS - and was rejected because there were too many people that live with migraine. Yes, really. In fact, they rejected it twice - despite finding it to be both clinically effective and cost effective - because the patient group is too large and uncertain. When the third application seemed to be doomed to the same fate, Novartis' Global Headquarters pulled the plug and gave up on a PBS listing in Australia. 

It is critically important that we get Aimovig on the PBS as it is the only drug in its class. Many have found Aimovig to be far superior, and there are a lot of people who had great results with Aimovig but poor results with Emgality or Ajovy. However, as the drug company has lost more than a million dollars on trying to bring Aimovig to Australia - most in giving away the drug for free and excessive government fees - they aren't willing to try again. Our only hope is for PBAC to review and remake their decision, and stop discriminating against migraine because it is a common condition.

Aimovig is currently available under a private script, costing about $800 if you order through a pharmacy or $695 if you order direct. 

GEPANTS

Gepants work like Aimovig in targeting the CGRP receptor, but are tablets rather than monoclonal antibodies, and can be either acute or preventative medications. Nurtec and Ubrelvy have been available in the US for some time but none of this new class of migraine medications is available in Australia yet. 

NURTEC (rimegepant)

STATUS: Not yet submitted to TGA or PBS. 
NEED: Australian distribution deal.

Nurtec is a gepant, a small molecule CGRP antagonist that targets the CGRP receptor, and is taken orally as a dissolving tablet. It is a long acting medication lasting on average 11 hours, and quite revolutionary as the first to be approved for both acute and preventative treatment. If you want to take it at the start of an attack like a triptan, you can do that. If you want to take it regularly as a preventative you can do that. If you want to mix and match - take acutely when you need, and take preventatively when you're expecting an attack (like for example if you get menstrual migraine, or your exercising, or are under some extra stress) you can do that too. 

We have been in discussions with a company that is negotiating a distribution deal for Nurtec (the developer, Biohaven, does not have an Australian office) but the very earliest that Nurtec might be available in Australia is 2023.

UBRELVY (ubrogepant)

STATUS: Not yet submitted to TGA or PBS. 
NEED: TGA approval and PBS listing.

Ubrelvy is another of the gepant class targeting the CGRP receptor, taken as a tablet for acute treatment of migraine attack (like a triptan). Ubrelvy is available in two dosage strengths and lasts about 5 hours. We have been talking to AbbVie about Ubrelvy and are keeping tabs on things, but don't have a timeline for Australia distribution as yet. 

Atogepant

STATUS: Not yet submitted to TGA or PBS. Expected to be approved by FDA September 2021.
NEED: TGA approval and PBS listing.

Atogepant is another gepant class medication targeting the CGRP receptor but this one was developed as a preventative. This is a really good option for those who would prefer a tablet to the mAb injectables, with very similar numbers of over 50% experiencing a 50% reduction in attack frequency and around a quarter of people being super-responders with complete or near complete freedom from migraine attack. It is available in three dosage strengths giving some flexibility to management as well. We expect atogepant to be approved in the US very soon, at which point we'll find out the brand name,  but there isn't a timeline for Australia as yet. 

Zavegepant

STATUS: Not yet submitted to TGA or PBS. 
NEED: TGA approval and PBS listing.

Zavegepant is an acute treatment gepant being designed specifically to be deliverable in lots of different ways. You'll see a lot more of this as there is greater recognition of the challenges that nausea and vomiting present for migraine management, which is great! As well as a tablet, Zavegepant is being developed as a nasal spray and injectable form. The development of Zavegepant has taken an unexpected turn with trials underway to use it in COVID-19 treatment. 

TRIPTANS

Triptans are not new, there are currently five available in Australia: Imigran (sumatriptan), Relpax, Maxalt, Naramig and Zomig. However, there are a couple that never came to Australia, and a number of triptan combination products we're going to try and bring to the market as well. Triptans are selective serotonin receptor agonists that work to relieve migraine attack by narrowing blood vessels around the brain, blocking pain signals from being sent to the brain, and stopping the release of certain natural substances that cause pain, nausea, and other symptoms of migraine attack. 

FROVA (frovatriptan)

STATUS: Not yet submitted to TGA or PBS. 
NEED: Australian distribution deal.

Frovatriptan is a long acting triptan, and the newest of the triptan class, but one of the drugs that just never came to Australia. It has been well trialed and is recommended in a number of national guidelines for effective prevention on menstrual migraine attacks by taking it for the week before your period. Read the research

AXERT (almotriptan)

STATUS: Not yet submitted to TGA or PBS. 
NEED: Australian distribution deal.

Almotriptan is a newer triptan that has less side effects than most other triptans and is safer for children. It was never brought to Australia. 

TREXIMET/SUVEXX (sumatriptan + naproxen)

STATUS: Not yet submitted to TGA or PBS. 
NEED: Australian distribution deal.

This combination product puts two generic drugs - the common triptan sumatriptan (Imigran), and the NSAID naproxen (Naprogesic and other brands) - into a single tablet. The two react against each other to be more effective. Treximet has been in the US since about 2011 but has been very slow to roll out in other markets, and has never come to Australia. 

QTRYPTA

STATUS: Not yet submitted to TGA or PBS. 
NEED: Australian distribution deal following FDA approval.

Qtrypta is a new product still awaiting FDA approval that delivers an old triptan called zolmitriptan (Zomig) in a patch that you put on your skin. It has been around for a while but the FDA made them do another trial so has taken a little longer than expected to come to market. 

AXZ-07

STATUS: Not yet submitted to TGA or PBS. 
NEED: Australian distribution deal following FDA approval.

AXS-07 is the development name of another triptan combination product, this one combining Rizatriptan (Maxalt) and the NSAID meloxicam. As a combination of two generics it is not expected to have a very difficult journey through the regulation process and is expected to be FDA approved this year. 

CL-H1T

STATUS: Not yet submitted to TGA or PBS. 
NEED: Trials to be completed

CL-H1T is still in stage three trials, but things look good for this triptan combination product being developed for those with significant nausea. This medication combines sumatriptan (Imigran) with a rapid release form of promethazine (Phernergan). As well as being an effective antiemetic, the promethazine appears to help the sumatriptan work better for greater reduction of other migraine symptoms as well. When it is approved by the FDA it will need an Australian distribution deal.

INJECTABLE SUMATRIPTAN

STATUS: Registered with the TGA, never submitted to the PBS
NEED: Listing on the PBS

Sumatriptan or Imigran is the oldest and most well-known triptan. Not many people know it is available in an injectable form. The injectable form is particularly useful for those who have rapid onset of severe attack, or are unable to tolerate anything orally due to vomiting and nausea. It is also really effective for people with cluster headache, and the ANZ Headache Society would like it listed on the PBS for both indications.  

DITANS

Ditans are a new class of medication that works like a triptan but is safe for people with heart conditions. At the moment there is only one Ditan product. 

REYVOW (Lasmiditan) 

STATUS: Not yet submitted to TGA or PBS. 
NEED: Trials to be completed

Reyvow is the first ditan taken as a tablet to manage migraine attacks. There are some side effect concerns and it is not better than triptans in managing migraine attack, so we expect this may not be listed on the PBS, or if it is, it will only be for people with heart conditions who are contraindicated for triptan and CGRP use. Lilly has advised that it is not likely to come to Australia until 2023.

ERGOTAMINES

Ergotamines are really old medications - it's what we had before triptans. Ergotamine is an alpha adrenergic blocking agent that also constricts blood vessels in the brain and acts as a seratonin antagonist. There is still a clinical need for access to these medications for people who don't get relief from triptans, and some companies are working on safer and more effective versions. The ongoing demand for ergotamine medications from both doctors and patients despite the risks and side effects is not surprising to anyone who knows how awful migraine can be, but it is challenging to get pharma companies to take the risk to keep providing these medications. 

Methysergide

STATUS: No longer produced.

We keep this one on the wish list in case we find a producer, but most companies have stopped making this tried and true medication due to significant side effects with long term use. Research of members of the International Headache Society found most believe it to be a good option for those who have failed other treatments and would still prescribe it... if only you could get it. This has previously been both TGA approved and on the PBS, so reactivating it should a supplier be found should not be too difficult. 

Cafergot

STATUS: Withdrawn from Australian market
NEED: Australian supplier. 

Another oldie but a goodie, Cafergot is a combination of caffeine and ergotamine that a number of Migraine Australia members still get from compounding pharmacies. It is still available in some other countries as both a tablet and a suppository, so we'll do our best to try and get it back. It was previously approved by the TGA and on the PBS. 

TRUDHESA

STATUS: Not yet submitted to TGA or PBS. 
NEED: Australian distribution deal.

Trudhesa is a new delivery format of Dihydroergotamine (or DHE) for migraine attack relief for up to 48 hours. Unlike triptans, DHE can be administered at any point in the migraine attack, but it has been challenging because it was really only available in injectable form and therefore limited to doctors administering it. A number of attempts to find different ways to deliver it have failed, but Trudhesa has succeeded with their fine mist nasal delivery technology and this product should be FDA approved by September. Impel NeuroPharma is a very small company with no Australian presence so it will need a distribution deal. 

PACAP INHIBITORS

PACAP or pituitary adenylate-cyclase-activating polypeptide was one of the other important chemicals identified when the role of CGRP was discovered. PACAP antagonists may be another breakthrough in migraine medication, and particularly for those who do not respond to CGRPs or have autonomic symptoms, but the science is proving challenging. There are still two PACAP inhibitors that we know of in development, Lundbeck's LU AG09222 and Lilly's LY3451838. Amgen's AMG 301 was terminated after failing phase 2 trials. 

VESTIBULAR MIGRAINE MEDICATIONS

With the anecdotal evidence pointing to CGRP medications not being very successful for those with vestibular migraine, it is more important than ever that we find good treatment options for this important part of our community. Diagnosis of vestibular migraine is on the increase with increasing recognition that migraine isn't a headache, so we expect demand for vestibular migraines will increase. The two identified so far are available through a complicated and limited special access scheme, and the drug company that makes them (Janssen) says they're happy to keep providing them under that program but they are not interested in developing an Australian pack or putting them through the TGA and PBS processes. They're both generics, so we'll try and find a more cooperative supplier. 

Flunarizine

STATUS: Available under a TGA Special Access Scheme (Cat C)
NEED: Listing with TGA and PBS

Flunarizine is a calcium channel blocker that is widely prescribed as a migraine preventative throughout Europe. It is generally used as an option when other medications haven't worked, but it is particularly effective medication for vestibular migraine patients. As far as we can tell, the only reason it isn't on the ARTG and PBS is that it was developed before the TGA and PBS existed, and now one ever brought it to market afterwards. You can get it if your doctor is prepared to do the SAS paperwork and you have a pharmacy willing to order it in for you.  

Cinnarizine

STATUS: Available under a TGA Special Access Scheme (Cat C)
NEED: Listing with TGA and PBS

Cinnarizine is an antihistamine and calcium channel blocker used as an acute medication for vestibular symptoms. Like Flunarizine you can get it through a special access program. 

A combination product, Cizinate, which combines cinnarizine with a common antihistamine Dimenhydrinate, is available now but most doctors don't know it exists. You don't need to do an SAS for it but your pharmacy will likely have to order it in. The company the provides does not appear to be interested in progressing a PBS listing. 

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