Gepants

A new treatment for migraine

New treatments

Recently there has been a lot to get optimistic about in terms of treatments for migraine. After years of using repurposed medicines, or medicines developed for other conditions, there are now specific preventive treatments developed for migraine. Four injectable calcitonin gene-related peptide (CGRP) monoclonal antibodies have been developed and approved for use on the NHS in the UK.

The gepants come as tablets and can be compared to the triptans in their role as an acute treatment, to treat a migraine attack. They should be taken at the start of an attack, as early as possible, to treat pain and associated migraine symptoms (e.g. nausea, light/noise/smell sensitivity). Some gepants can also be used as a preventive treatment for migraine, if prescribed for this use, with an oral tablet being taken every other day, to help reduce the severity and frequency of attacks.

Gepants

There are currently three gepants – Ubrogepant, Atogepant and Rimegepant, and others in development. They are CGRP receptor antagonists.

Compared to conventional acute treatments such as triptans, non-steroidal anti-inflammatory drugs (NSAIDs), and other painkillers, the gepants don’t seem to cause rebound or medication overuse headache.

How do they work?

At the start of the migraine process, CGRP is released by the nerves, and this helps to prolong and sustain the migraine attack. Gepants bind to that CGRP receptor on the trigeminal nerve and block this effect. Triptans on the other hand, suppress the release of CGRP and act on different receptors.

Gepants and triptans bind to the blood vessel. However, gepants (unlike triptans) do not constrict or tighten the blood vessel. They prevent it from dilating.

This makes them safer for people with heart issues and they can be used in people with cardiovascular disease. Therefore, gepants may be an option for people who can’t take triptans, such as those with heart related risks, those who find triptans ineffective or have had unpleasant side effects.

Early indications suggests that gepants may be the first acute treatment not associated with medication overuse headache. Due to this, they may also be used as a preventive treatment, if prescribed for this use, making them among the first oral (tablet) CGRP treatments to prevent migraine.

What are the side effects?

The most common side effects of the gepants reported in clinical trials have been fatigue, nausea, dizziness, tiredness and dry mouth. You should let your doctor know about all other medications you are taking to be cautious of medication interactions.

Availability

NICE / SMC approval is required for use on the NHS. The table below shows the licence and approval status of gepants in the UK.

The gepant treatments currently developed are listed in the table below. However they are not yet all licenced and available for use in the UK. Licences are granted by the MHRA. The Medicines and Healthcare products Regulatory Agency (MHRA) is the UK body responsible for ensuring that medicines and medical devices work and are safe to use. An MHRA licence will also allow a treatment to be used privately.

Name NHS Review/Approval (NICE/SMC)* MHRA Authorisation** Route Use
Atogepant Scotland – preventive and acute

England, Wales, and Northern Ireland – under review

Yes Tablet Preventive
Rimegepant England – preventive and acute

Scotland – preventive and acute

Northern Ireland- preventive only

Wales – preventive and acute

Yes Tablet Acute/preventive
Ubrogepant No review date yet Not yet Tablet Acute
Zavegepant No review date yet Not yet Nasal spray Acute

*NICE=National Institute for Health and Care Excellence; SMC= Scottish Medicines Consortium
**The Medicines and Healthcare products Regulatory Agency (MHRA).

The Migraine Trust will continue to publish updates when new treatments get approved and become available on the NHS.

Benefits of new treatments

The availability and access to new migraine treatments will make an enormous difference to the lives of many people affected by the debilitating impact of migraine. It will give doctors more options to prescribe from, especially to people who have other conditions or experience side effects that limit their treatment options. Understanding migraine better and developing precise medicines to target migraine will also help to remove some of the stigma people with migraine face.