Completed Trials Archive

What does the drug do?

Arimoclomol works by protecting cells from accumulation of misfolded proteins by using the cell's natural defence mechanism, the heath shock response, resulting in production of protective heat-shock protein (HSPs) in stressed cells. HSPs can also direct the removal of the abnormal proteins when folding is not feasible. 

Trial Outcome 

Arimoclomol was tested in phase 2 and 3 clinical trials. Despite initial potentially promising signs in the phase 2 trial, the larger phase 3 did not meet its primary or secondary endpoints to show benefit in people with MND. Results from the trial can be found here.

What does the drug do?

CNM-Au8 is an oral liquid suspension of gold nanocrystals designed to improve nerve cells’ survival, function, and communication by supporting their energetic needs, while lowering oxidative stress. Laboratory studies, in models of MND, have shown that CNM-Au8 can improve nerve cell survival and motor neurone function.

Trial Outcome

The Phase 2 trial (RESCUE-ALS) investigated the safety and efficacy of CMN-Au8 in 45 people with MND for 36 weeks. The trial did not meet its primary endpoint, which looked at the change in a marker of motor neurone loss (Motor Unit Number Index - MUNIX). However, additional data from the trial, including the open-label extension, showed potential signs that people who received CMN-Au8 earlier and for longer had a survival benefit. This trial was small and trends in each of the measures favouring CNM-Au8 suggest that a larger trial, better powered to see subtle, but potentially meaningful effects, will be valuable. This is one of the reasons CNM-Au8 was also trialed in a much larger clinical trial - the Healey Platform Trial. The results from this trial also highlighted a potential survival benefit, but this trial also did not meet its primary endpoint of changing the rate of disease progression. 

What does the drug do?

Edaravone was originally developed to treat acute ischemic stroke. One theory about why motor neurones die in MND is that they are affected by oxidative stress. Cell’s normal metabolic processes can cause oxidative stress, but in MND the metabolism can be heightened and increase the impact of oxidative stress. This can result in cellular damage resulting in excessive accumulation of free radicals. Edaravone acts as a ‘free radical scavenger’ helping to reduce the effects of oxidative stress, with the aim of slowing the progression of MND.

Trial Outcome

Treatment with Edaravone has showed some signs of beneficial effect in clinical trials. Other trials are underway, which are looking to see the impact Edaravone has on markers of the disease within the body (biomarkers). Both Oral and Intravenous Edaravone (Radicava) have been approved as a treatment of ALS in the United States and a select few other countries. Radicava was reviewed by the European Medicines Agency (EMA) but Mitsubishi Tanabe Pharma America withdrew the application. At the time of the withdrawal, the Committee for Medicinal Products for Human Use, of the EMA, was trending towards not approving Radicava. A different formulation of Oral Edaravone was tested in a clinical trial across Europe. This trial did not meet its primary endpoint, suggesting it was not beneficial for people with MND.  

What does the drug do?

ILB is a pleiotropic molecule which means it is believed to have multiple effects in the body. Its active component, a patented form of dextran sulphate, targets multiple pathways that are involved in the loss of function and death of neurons, which is characteristic of MND and other neurological diseases. It is administered via a subcutaneous (under-the-skin) injection.

Trial Outcome

The Phase 2 open label trial was stopped early due to the COVID-19 pandemic. 11 participants were enrolled into the study and took 2 mg/kg of ILB, by subcutaneous (under the skin) injection, once a week for up to 38 weeks. The trial found weekly ILB injections to be safe and well tolerated. Further research is needed to understand any potential benefit ILB may have for people with MND. You can read more about the trial here or in a pre-print article (please note pre-print articles have not been peer reviewed).

What does the drug do?

Levosimendan (ODM-109) is licensed to treat some forms of congestive heart failure by strengthening the action of heart muscle. It was hypothesised that Levosimendan might help to improve the function of the diaphragm muscle, one of the main muscles involved in breathing, and help maintain breathing capacity in people with MND.

Trial Outcome 

Levosimendan was tested in phase 2 and 3 clinical trials. Despite initial potentially promising signs in the phase 2 trial, the larger phase 3 did not meet its endpoints to show benefit in people with MND.

What does the drug do?

Memantine is an existing drug which is used for the treatment of Alzheimer’s disease. It works by blocking the action of glutamate, a chemical in the brain which helps to pass messages between the neurons. Increased levels of glutamate have long been associated with neuron damage as excessive amounts are toxic to the cells. Glutamate is known to have links to MND, with increased levels being found in the blood and cerebrospinal fluid (CSF) of those with MND.

Trial Outcome 

Memantine was tested in a phase 2 clinical trial, which did not meet its primary or secondary endpoint of slowing disease progression as measured by ALSFRS-R. Memantine was also tested in the MND SMART platform trial in the UK, but testing was stopped early after interim analysis found that memantine was highly unlikely to be beneficial to people living with MND. 

What does the drug do? 

Nuedexta is a drug that treats emotional lability (‘pseudo-bulbar affect’, or PBA) in MND and other neurological conditions. Emotional lability can be described as inappropriate emotional expression often characterised by uncontrollable laughing or crying; it is a feature of MND and some other neurological conditions.

Trial Outcome 

Nuedexta was shown to be beneficial in treating emotional lability. However, the drug is not available for patients in the UK and EU. This is because the drug the company who owns Nuedexta withdraw the marketing authorisation for Nuedexta in the EU in 2016 and did not take the necessary steps to make it available in the UK. 

What does the drug do?

Pegcetacoplan inhibits the activity of a protein called C3, which is involved in a specific immune response called the complement system. Incorrect activation of the complement system can cause inflammation and damage to healthy motor neurons. C3 protein levels have been found to be increased at the junction between nerves and muscles in people with MND. Pegcetacoplan is designed to block the action of the C3 protein and reduce inflammation which was theorised to help to slow disease progression.

Trial Outcome 

Pegcetacoplan was tested in a phase 2 clinical trial. The drug was found to be safe and well tolerated but the trial did not meet its primary or secondary endpoints, suggesting pegcetacoplan does not have a clinical benefit for people with MND. Development of pegcetacoplan for the treatment of MND has been discontinued. 

What does the drug do? 

Reldesemtiv is a muscle activator that increases force (contraction) and power of skeletal muscles and delays muscle fatigue. Instead of aiming to slow down progression of MND, the drug was designed to increase quality of life by increasing muscular strength.

Trial Outcome 

Reldesemtiv was trial in phase 2 and 3 clinical trials. Despite initial potentially promising signs in the phase 2 trial, the larger phase 3 trial was ended early. Interim analysis found there was no evidence that reldesemtiv had a beneficial effect for people with MND.

What does the drug do?

RT001 is made from slightly modified linoleic acid (LA). Linoleic acid is typically part of a normal human diet and is found in most oils. RT001 can protect cells from lipid peroxidation – a process that is believed to cause damage in several neurodegenerative diseases, including MND.

Trial Outcome
The results of the phase 2 clinical trial found that those who received RT001 had a small slowing in disease progression compared to those who took the placebo. However, this was found not to reach statistical significance due to the small size of the study. The results did show a potential that the treatment is more beneficial for those with severe disease, however an additional, larger, trial is needed to confirm these results. 

What does the drug do?
Tegoprubart is an antibody against a protein called CD40 ligand (CD40L) which is present on the surface of some immune cells. Antibodies are proteins that bind to and block a particular target. CD40L plays a role in regulating the immune response and that can trigger inflammation in the spinal cord. Research has shown that the CD40L pathway is overactive in people with MND. By inhibiting CD40L, AT-1501 could block or delay the activation of the damaging inflammatory immune response which could delay the onset or slow the progression of MND and increase survival.

Trial Outcome
The results of the phase 2 clinical trial found tegoprubart to be safe and well-tolerated in people living with ALS. They also found that the drug hit the target pathways within the body, with some ALS biomarkers (biological signals of the disease) being reduced.

What does the drug do?

WVE-004 is specifically designed for MND caused by a mutation in the C9orf72 gene. WVE-004 uses an approach known as ‘antisense’, where the drug directly interferes with the faulty instructions for making a protein. The C9orf72 gene contains three different sets of instructions (RNA) to make the C9orf72 protein and these three RNA are called V1, V2 and V3. In some forms of MND, mutations in the C9orf72 gene cause the V1 and V3 instructions to be faulty and this leads to the production of toxic proteins which build up in the neurons. WVE-004 targets the faulty V1 and V3 instructions and signal to the cell that they need to be destroyed, leaving the V2 instructions functional so that healthy version of the C9orf72 protein can still be made.

Trial Outcome 

WVE-004 was tested in a phase 1b/2a clinical trial. While WVE-004 was found to reduce levels of the toxic proteins thought to play a role in C9orf72 MND, it did not have any clinical benefit for people with MND. The development of WVE-004 has been discontinued.