A drug that can help prevent migraines could soon be available on the NHS. Atogepant (brand name: Aquipta) was recently recommended by the National Institute for Health and Care Excellence (Nice) to prevent episodic and chronic migraine attacks. The drug would be recommended to people who have at least four migraine days a month or where at least three previous preventative treatments have failed.
Author
Anna Andreou
Senior Lecturer and Director of Headache Research, Consultant clinical scientist; King's College London and Guy's and St Thomas' NHS Trust, King's College London
Migraine is a complex neurological condition that affects about 10 million people in the UK. It's characterised by recurrent, severe headaches that can be made worse by physical activity and are often debilitating. They're accompanied by other neurological symptoms such as aura (usually vision disturbances, such as flashes or light or blind spots), sensitivity to light or sound, nausea and vomiting.
About 1% of the population suffer from chronic migraine attacks. This means they have 15 or more headaches days a month, with at least eight of these headaches having migraine characteristics. Both episodic and chronic migraine attacks have a significant effect on a person's quality of life, as they may miss out on social activities and work.
Until now, the first options migraine patients had to prevent attacks was to use either blood pressure drugs or anticonvulsants. But many people prescribed these drugs for migraine attacks stop using them because they either aren't effective or because of the side-effects they cause - such as dizziness, tiredness and slow speech.
But atogepant has been specifically developed to prevent migraines.
Atogepant belongs to a new group of drugs named gepants. More specifically, it is a calcitonin-gene related peptide (CGRP) receptor antagonist.
CGRP is a small protein that circulates at elevated levels during a migraine. People who have chronic migraine consistently have higher levels of CGRP in their system. It's believed that CGRP is produced by neurons that provide sensory information to the head and neck. When CGRP activates the CGRP receptor, it's thought to contribute towards the development of the migraine headache.
But atogepant blocks this receptor, preventing it from becoming activated and stopping migraines from developing. It's the first oral daily treatment that blocks the CGRP protein approved for both episodic and chronic migraine. Other treatments that prevent attacks by blocking the same protein have to be injected to work.
Another gepant recently approved by Nice is rimegepant, which is to be taken once every other day. However, it's only suited to patients who suffer from episodic migraines - whereas atogepant can be used by people who have both chronic and episodic migraines.
Consistently effective
Three clinical trials have shown atogepant to be safe and effective for people with episodic or chronic migraines.
The Advance trial evaluated how safe and effective different doses of atogepant were compared with a placebo in preventing episodic migraine. Participants were aged 18 to 80 years of age. Over the 12-week period, all doses of atogepant were shown to reduce the average number of migraine days participants had per month.
Participants who received a 60mg dose of atogepant suffered four fewer migraine days on average. Those who received the placebo only had two-and-a-half fewer migraine days.
Another trial, the Progress trial, explored what effect different dosages of atogepant had in participants who suffered from chronic migraine. The researchers compared a 60mg daily dosage and a 30mg twice-daily dosage of the drug against a placebo.
They found that both dosages significantly decreased the average number of migraine days participants had per month over the 12-week trial period. The 60mg once-daily tablet was found to be well tolerated and effective, leading to nearly seven fewer migraine days per month.
A third trial, the 302-LTS trial, followed participants who suffered from episodic migraine for over a year, finding that atogepant was consistently effective for reducing migraine attacks. At the beginning of the study, atogepant led to an average of five fewer migraine days per month. By the end of the study, participants had an additional benefit of more than 30% fewer migraine days per month.
Atogenpant was consistently shown to be safe across all studies, including the one that lasted for a year. Any side-effects related to the drug were mild. The most common ones, affecting more than 5% of participants, were constipation, upper respiratory tract infections and nausea.
No serious cases of liver disease were reported, which used to be a problem with older generations of gepants. Atogepant's safety has not been tested in pregnant or lactating women.
Based on these trial results, Nice has recommended atogepant be made available as a 60mg tablet that can be taken orally once daily - with or without food.
Atogepant is the only once-daily oral CGRP receptor antagonist available for preventing and treating both episodic and chronic migraine. This offers more choice to people with migraine when it comes to treatment - especially those who might prefer taking a daily tablet over getting a CGRP monoclonal antibody injection or Botox injections.
Another benefit of atogepant is that it can be stopped quickly should a person experience any serious side-effects or become pregnant.
Although it's difficult to predict who may respond best to atogepant, it provides people who suffer from migraine with another treatment option - and may lead to a better quality of life.
Anna Andreou receives funding from the Medical Research Foundation and Brain Research UK. She also received research funding from eNeura, AbbVie and Pfizer. She is affiliated with the International Headache Society, being elected as a Trustee of the Board. She is Chair of the Headache special interest group of the British Pain Society.
