Last month saw the two-year anniversary since the first COVID lockdown in England (the UK) which changed our lives forever – not least because of the distress and disruption caused to all of us – including MND research and the ability to perform and complete clinical trials here in the UK and across the world. After the frustration of the last couple of years, we all now hope to move away from restrictions and the pace of MND research and clinical trials can return and continue to grow.
Thankfully it looks as though this hope and positive outlook is coming to fruition – thanks to the dedication, generosity and commitment of the entire MND community.
As such, this year is set to be an exciting time for MND research, and we are especially hopeful that MND clinical trials will take centre stage in the coming months. During 2022 we are expecting new trials to begin recruitment in the UK, other trials to readout their results and decisions to be announced by authorising bodies for potential treatments that have completed trials for MND.
We know how important being up to date on the latest trials is to the MND community so we will always endeavour to keep you updated with all the latest news and updates. For the latest information you can follow us on twitter, sign up to our research monthly newsletter or check out our latest news page.
In this two-part blog, we discuss what trials to keep an eye out for this year, including those that are starting, reading out results and awaiting announcements from approval bodies on trials that have completed.
In the first part of this series, we give a rundown of all the new MND trials expected to start recruiting in the UK this year.
“Usually, we have on average one trial or less to offer people coming to our Motor Nerve Clinic. We currently have six in the final stages of set-up, two recruiting nationally (not even including gene therapy trials), and we also have the MIROCALS trial ready to be analysed. This huge increase in activity is a reflection on the excitement in the MND research community that this is a condition that can be cured, something which until recently, was regarded as impossible.”
Prof Ammar Al-Chalabi, King’s College London
Tofersen (ATLAS)
Tofersen, a form of precision therapy for people with SOD1-related MND, is being investigated as a potential treatment for SOD1-MND. It is an antisense oligonucleotide (ASO), which targets the genetic instructions for the faulty SOD1 protein and aims to reduce or prevent the faulty disease-causing protein from being made. You can read more about how Tofersen works in a previous blog here.
In short, there are two recent clinical trials which investigate tofersen as a treatment for MND. The first is a phase 3 trial, called VALOR, which investigated the effectiveness of Tofersen in people living with MND with the SOD1 mutation. Results of this trial were announced in 2021. Although the trial didn’t reach its primary endpoint, it did show that early access to Tofersen led to less decline across secondary outcome measures, including reduced levels of SOD1 protein in the cerebrospinal fluid (CSF). You can read more about the results of VALOR in a previous blog here. This led to the second phase 3 trial, known as ATLAS, will help to determine the point in time tofersen should be administered for maximum benefit and the impact on disease onset. This trial aims to investigate the benefit of tofersen in those who have the SOD1 gene mutation but who do not yet have clinical manifestation of MND, so are considered pre-symptomatic. The trial is expected to start in the UK in the coming months. You can read more about the trial here.
AMX0035 (Phoenix)
AMX0035 is a combination therapy, made up of two compounds – TUDCA and Sodium Phenylbutyrate. The combination of both these compounds is believed to improve the survival of neurones. TUDCA is thought to increase the threshold for cell death by blocking key cell death pathways. While Sodium Phenylbutyrate reduces the stress on the endoplasmic reticulum (ER), part of the cell which maintains the balance of proteins.
The results of the phase 2 trial, known as CENTAUR, were released in late 2021 and showed some encouraging results, suggesting that over the 2-year trial people who started the treatment earlier lived longer than those who started the treatment 6 months later. The data from this trial is currently being evaluated to see if the drug should be approved and you can read more about this approval decision in the second part of this blog series. Nevertheless, further testing of the drug is still underway through a phase 3 trial, known as PHOENIX, which aims to further investigate the effects of AMX0035 in people living with MND. The trial is expected to start later in the year, at a variety of sites over the UK. You can find out more about the trial here.
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MAGNET (Multi-arm, Adaptive, Group-sequential trial NETwork) Platform trial
TRICALS, a European, Australian & Canadian research initiative to find a cure for ALS, announced in March 2022 that the MAGNET (Multi-arm, Adaptive, Group-sequential trial NETwork) platform trial has begun recruiting participants. This is a clinical trial in which multiple treatments for ALS are investigated simultaneously – known as a platform trial. The trial has had funding from a range of funders, including the MND Association.
The first drug to be investigated in the platform trial is lithium carbonate. Lithium carbonate may benefit people living with MND who have the UNC13a mutation, a gene known to be associated with MND. This concept emerged due to data from previous clinical trials testing lithium chloride in people with MND. After these trials completed researchers returned to the data and compared any effect of the treatment with new genetic information gathered from each participant. The data suggested that lithium carbonate treatment might be effective in a subset of people who were carriers of a genetic change in a MND associated gene called UNC13a. Therefore, this new trial is testing lithium chloride in people with MND and the UNC13a gene change. You can read more about how lithium carbonate works in a previous blog here.
Although the trial has already began recruiting in other countries in Europe, it is still currently “in preparation” in the UK. This means that it is undergoing the required ethics and regulatory approval before the trial can begin. We will provide more information about recruitment and trial sites when these are available. You can find out more about the trial here.
Lighthouse II
One possible trigger of MND is thought to be the activation of genetic material from ancient viruses (retroviruses) which was left in our DNA during evolution. One of these ancient viruses, known as HERV-K, is thought to sit dormant within us all but may become re-activated in some people and has been suggested to play a role in the development of MND symptoms. Triumeq is a mix of three drugs. These are known as ‘antivirals’ which as the name suggests can prevent viruses from harming us. Antivirals are used in HIV and more recently against COVID-19. Together these drugs block an enzyme know as integrase. Without this enzyme the virus cannot make new copies of itself and this leads to the reduction in the amount of these activated viruses in the body.
The phase 2, Lighthouse, trial showed some encouraging results, including a statistically significant reduction in disease progression, measured by the ALSFRS-R. You can read more about these results here. Building on the initial Lighthouse trial is a phase 3, placebo-controlled trial called Lighthouse II. This trial, partly funded by the MND Association, will further investigate the potential of using Triumeq as a treatment for MND in a larger cohort. The trial is currently “in preparation” but is thought to start recruiting in the coming months. You can find out more about the trial here.
Edaravone (ADORE)
Edaravone (Radicava) is already approved by the FDA, in the US, Canada, Japan and South Korea for the treatment of MND, but only in an intravenous form which involves a slow and inconvenient intravenous infusion with a regime consisting of a cycle of an infusion every day for 10 days followed by 10 days off. Edaravone is thought to work by reducing the effects of oxidative stress, which is thought damage motor neurones.
Over the years, researchers have been investigating oral forms of Edaravone. This new phase 3 trial (ADORE), looks at investigating one formulation of oral edaravone, known as FAB-122. This trial will build on the phase 1 trial which showed FAB-122 to be safe and tolerable. The trial is currently “in preparation” in the UK and should be recruiting in 2022. You can find out more about the trial here. You can also read about another oral formulation of Edaravone, known as MT-1186, which is awaiting a decision on FDA approval in the second part of this blog series.
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Trimetazidine (MetFlex)
It is known that changes in metabolism and the way energy is used in the body can occur in MND. A new phase 2a trial, known as MetFlex, will investigate a drug called Trimetazidine. Trimetazidine is already used to help treat angina but has shown some promise in slowing MND disease progression by reducing heightened metabolism and oxidative stress. MetFlex is an open label trial and will investigate the drug’s safety and tolerability in people living with MND. The trial will also look into markers of oxidative stress within the body to see if the drug helps to reduce this oxidative stress as thought. The trial has already began recruiting in Australia and the Netherlands and is expected to start recruiting in the UK in 2022. You can find out more about the trial here.
We know how important being up to date on the latest trials is to the MND community so we will keep you updated as soon as we know more information on when and where these trials will start recruiting. For the latest information you can follow us on twitter, sign up to our research monthly newsletter, check out our latest news page or our treatment trials page.
I have recently been tested and carry the SOD 1 gene. My brother died 2 years ago, he too had that gene, along with 3 of my cousins. As yet I have no symptoms (I am 70 this year). Our father lived to be 93 and showed no symptoms of MND but he must have carried the gene and passed it down to my brother and I. Our dads eldest sister must have been a carrier too as she passed it to her eldest son, also passing it down to her second eldest son (who didn’t have MND) but he passed it down to his two eldest children who died from it.
If I can be of any help to a trial I am happy to do so. I live in Yorkshire
Hi Gillian,
Thank you for your comment and we are sorry to hear about the impact MND has had on you and your family. Thank you for your amazing offer to help with MND research in a clinical trial. There is a clinical trial, called ATLAS, which will seek to determine the value and optimal timing to begin treatment with a drug known as Tofersen in people who have the SOD1 gene mutation but have not yet started to show symptoms, such as yourself. You can read more about this trial here. The trial is currently not yet recruiting in the UK, but will be in the coming months. We will make sure to update the community as soon as we have more information about when and where the trial will be recruiting. Best wishes, Charlotte