New and effective treatments for MND are urgently needed and many scientists around the world are working towards this goal. Throughout 2024, we saw many new clinical trials beginning across the globe as the pace of MND research continues to grow. This momentum is continuing into 2025, with clinical trials set to begin and release results. In this blog we will highlight some of the most anticipated updates from MND clinical trials happening across the world that we are expecting this year.
International trials expecting results this year
AP-101
AP-101 is a drug which is designed to target the faulty SOD1 protein which is made in people with MND who have a change in the SOD1 gene. These changes lead to clumps of faulty SOD1 protein within neurons which is toxic and can cause damage and neuron death. AP-101 is designed to stick to the clumps of SOD1 protein to prevent them from causing damage to the cells and help to remove them. Studies in the lab have shown that AP-101 has been shown to slow the progression of the disease and prolong survival.
A phase 2a trial of AP-101 is investigating the safety and tolerability of AP-101 in people with MND, as well as looking at how it works in the body. The trial is comparing AP-101 to a placebo for up to 48 weeks and testing different doses of the drug. Top-line results from this trial are expected this year.
Ambroxol
Lipids are fatty compounds which play an important role in the body, such as storing energy and controlling what goes in and out of cells. It has been found that the breakdown of lipids may change in MND. Ambroxol is an existing drug which is used to treat respiratory diseases and break down the production of excess mucus. It is being tested as a potential treatment for MND, as it might help to correct the lipid changes that happen in cells in MND. Previous lab studies have shown that the drug may help to improve motor neurone function, muscle strength and protect motor neurons.
A phase 2 trial of Ambroxol, called AMBALS, is looking to see if the drug could be safe and effective for people with MND. It is testing Ambroxol in people with MND in Australia and those on the trial will either get the drug or a placebo for 24 weeks. There is also an open label phase where everyone has the chance to receive the drug for a further 6 months. Results from this trial are expected to be released in the coming months.
Masitinib
Inflammation in the brain and spinal cord is thought to play a role in the progression of MND. It has been suggested that reducing inflammation in the brain may help to reduce the damage to motor neurons and slow the progression of the disease. Masitinib is a drug which is designed to block the action of a protein which is involved in inflammation in the body. A previous phase 2/3 trial suggested that masitinib might be beneficial for a subgroup of people with MND.
This phase 3 trial is further testing masitinib in this subgroup of people with MND to determine whether the drug is beneficial and able to slow disease progression. It is testing two different doses of masitinib alongside riluzole for 24 weeks and comparing these with those on a placebo alongside riluzole. The top-line results of this confirmatory trial are expected this year.
Metformin
Metformin is an existing drug which is used in the treatment of diabetes to help control blood sugar levels. It is being investigated as a potential treatment for MND for people who have changes in the C9orf72 gene. Changes in this gene cause toxic proteins to be made in neurons which can cause damage and neuron death. Studies in the laboratory have suggested that metformin might be able to reduce the number of toxic proteins that are made due to the C9orf72 gene change . The drug is thought to block a key pathway in cells that is essential to the production of these toxic proteins.
Metformin is being tested in a phase 2 trial to see if it is safe, well tolerated and beneficial for people with MND. The trial is an open label study meaning that everyone on the trial gets the drug and there is no placebo. The results of this study are expected to be announced this year.
International trials expecting to begin this year
PrimeC
PrimeC is made from a combination of two existing prescription medicines, an antibiotic called Ciprofloxacin and a non-steroidal anti-inflammatory agent called Celecoxib. It is thought to target three key biological features of MND. These include inflammation in the brain, abnormal microRNA activity (small molecules help to control the activity of other genes) and the build-up of iron in neurons.
All of these have been suggested to contribute to the damage of motor neurons in MND and reducing them could help to limit the damage to neurons and slow disease progression. A previous phase 2 trial of PrimeC showed promising signs of slowing disease progression and identified a subgroup of people with MND who the drug may be more effective for.
A phase 3 trial is planned to begin in 2025 which will test the drug in around 300 people with MND to see if it could be an effective treatment by comparing those on PrimeC to those on placebo. Participants will then be given the chance to enter into an open label exetension, where everyone on the trial can take PrimeC for a longer period of time.
Last year, the company behind PrimeC had announced that they planned to apply to Health Canada for accelerated approval of the drug. If accelerated approval is granted, it will mean that people with MND in Canada will be able to access the drug while the phase 3 trial is running. The phase 3 trial results will determine whether the drug should be fully approved or removed from the market.
CNM-Au8
A phase 2 study, called RESCUE-ALS and it’s open label extension found that the drug may increase survival in people with MND who received CMN-Au8 earlier and for longer.
The RESTORE-ALS trial is a phase 3 trial which is further testing CNM-AU8 to determine whether this possible survival benefit can be confirmed. It will also investigate if the potential treatment can slow disease progression for people with MND. This trial is expected to begin in 2025.
The company behind the drug have also announced that they are planning to submit an application to the Food and Drug Administration (FDA) in the USA for accelerated approval of CNM-AU8. If accelerated approval is granted, it will mean that people with MND in the USA will be able to access the drug while the phase 3 trial is underway. The phase 3 trial results will determine whether the drug should be fully approved or removed from the market. This application for accelerated approval is expected to be submitted in the second half of 2025.
AMX0014
AMX0114 is a new potential gene therapy for MND and is designed to target the instructions for a protein called calpain-2. Calpain-2 has been found to be increased in people with MND and this increased activity is thought to be involved in causing damage to neurons. AMX0114 is thought to decrease levels of calpain-2 and has been suggested to improve neuron survival and reduce levels of a marker of disease activity called Neurofilament Light Chain (NfL).
A phase 1 trial of AMX0114, called LUMINA, has already begun in Canada and is expected to open more sites in Canada and the USA in 2025. This is first time that the potential treatment is being tested in people and the trial is investigating whether AMX00114 is safe and works within the body as designed. The LUMINA trial will recruit 48 people with MND who will be randomised to receive either the potential treatment or a placebo. This trial will reveal if the potential treatment is safe and whether it should be tested in larger trials in the future.
There are other clinical trials happening around the world and you can find out more about these on our website.
With so many clinical trials for MND happening across the globe , we know it can be hard to keep up to date with them all! We hope that this blog series has helped to give you a snapshot of the international clinical trial updates that we’re expecting this year. You can find more on the latest news in MND research on our website.
