Until recently there has been little hope for effective treatment for migraine, meaning that more than one billion people around the world who experience this severe and painful condition have had little respite. For the last five years, King’s research has been at the heart of the step-by-step progression through a series of clinical trials and regulatory approval of new drugs to treat migraine.
Migraine is a severe and painful long-term health condition. It is varied, complex and until recently there has been little hope for effective treatment, meaning that more than one billion people around the world who experience this condition have had little respite. For the last five years King’s research has been at the heart of the step-by-step progression through a series of clinical trials and regulatory approval of five new drugs to treat migraine.
Led by Professor Peter Goadsby, who has been working in this area for 35 years, this research has moved from identifying novel targets for treatment through to trials that have successfully shown several drugs to be safe and effective. As more and more people gain access to these drugs, they will be able to better manage this debilitating long-term condition.
I think the important thing about this research is that it shows a neuroscience-based approach has value and that bench and bedside research married together has the ability to change patients’ lives, and clinical practice. I’m humbled by the emails that we get from patients whose lives have been turned around by these medicines. We haven’t reached everyone, we have only just started. Crucially, what this research shows is that migraine is a tractable problemPeter Goadsby, Professor of Neurology, King’s College London & lead for pain research at NIHR Maudsley Biomedical Research Centre
Impact of migraine and lack of good treatments
It is estimated that there are 190,000 migraine attacks experienced every day in England. People who suffer migraine attacks can experience head pain, problems with sight, sensitivity to light, sounds and smells, fatigue and feeling sick, and often have a significant mental fog. Attacks can last up to three days and cause significant impact on people’s work, relationships and mental health, with 25 million days of work and education lost each year due to the impact of migraine.
When this body of research started there were no specific treatments to prevent migraine attacks, only those that reduced their effects. The available medicines were repurposed drugs originally developed for conditions such as epilepsy or high blood pressure. These drugs work slowly; are not effective in all migraine sufferers; and when effective, nearly half of patients have such severe side effects that they stop taking the treatment.
In early work in Australia, Prof Goadsby collaborating with his Swedish colleague Prof Lars Edvinsson, identified a small protein, calcitonin gene-related peptide (CGRP), which is released in sufferers during migraine attacks. This discovery has proved transformational for migraine research globally by suggesting that reducing the effect of CGRP will reduce the likelihood of a migraine attack.
Subsequent research by these researchers, who have been based at King’s since 2014, focused on creating novel drugs which do exactly this. Specifically, King’s research has unlocked the potential of two novel migraine drug classes: the first using antibodies that target CGRP or its receptor; the second based on small molecules, CGRP receptor antagonists (‘gepants’). This work led to the first drugs specifically designed to treat migraine.
Four specific antibodies were developed commercially to bind to the CGRP itself, or its receptors, as a means to reduce the levels of this protein. Studies by King’s and US collaborators, including industry, showed this approach was safe and effective.
King’s then led or collaborated on the next stage of clinical trials for three drugs (Erenumab, Fremanezumab and Glacanezumab) developed by different pharmaceutical partners. These trials were multi-centre and long-term and demonstrated that the drugs reduced the number of days on which migraine was experienced and alleviated their impact on daily activities. The clinical trials provided the evidence on which these drugs were granted approval for use by the US and European regulatory authorities between 2018 and 2022.
Migraine is giving up its secrets to our research efforts and this will benefit our patients now and their children in the futureProfessor Peter Goadsby
Recommendations for use
The National Institute for Health and Care Excellence (NICE) in England and Wales, and the Scottish Medical Council (SMC) in Scotland, are the UK bodies providing evidence-based guidance on the best and most cost-effective drugs and treatments available. Any new drug must be recommended by NICE or the SMC for use in the NHS.
King’s research was central to the appraisal and successful recommendation of the drug fremanezumab by NICE and the SMC, as well as NICE’s recommendation of galcanezumab and erenumab, for the treatment of both chronic and episode migraine.
Making migraine treatments accessible around the world
One of the downsides to antibody therapies is that they are complex and expensive to make, meaning that despite regulatory approval there is still a price barrier for their adoption by the NHS and other healthcare systems.
King’s research was integral to the development of a second, novel class of drugs which will ultimately be cheaper to manufacture. These drugs still work on the CGRP system but use small molecules instead of antibodies to reduce the levels of the protein. They are known as gepants.
Early trials by King’s and collaborators showed that gepants can relieve the symptoms of a migraine attack soon after treatment. King’s research provided evidence to support the FDA approval of rimegepant. A later study of rimegepant also showed that this class of drugs does not have the side-effect of headache caused by overuse of medicines, which is common to other treatments. For migraine sufferers, this is in itself a game-changer.
These regulatory approvals – and others in the pipeline – can potentially help millions of people who suffer migraines around the world because, when this class of drugs comes off-patent, gepants will be incredibly inexpensive to produce. This means that these early steps pave the way for phenomenal impact through migraine treatments which will have far greater reach, and can be made available to everyone, around the world.
The new drugs are already being used to treat more than 500,000 migraine patients in the US more effectively. NICE predict that 11,700 people in the UK can now receive fremanezumab and based on trials showing the drug to be effective in 45% of patients, predict that 5,300 migraine sufferers will therefore benefit.
With the recent further recommendation by NICE for the use of galcanezumab for not just chronic, but also episodic migraine, many more migraine sufferers in the UK will benefit.
Those migraine sufferers who have already received the treatment say that they have been given their lives back. Research shows that these novel therapies improve quality of life, particularly for migraine sufferers who have previously tried 2–4 unsuccessful treatments.