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?

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? 

NP001 acts on particular cells within the immune system in the bloodstream, which in turn influences inflammation within the brain and spinal cord. It was hypothesised that NP001 might be able to reduce inflammation which is known to damage motor neurons in people with MND. 

Trial Outcome 

NP001 was tested in phase 1 and 2 clinical trials. The drug was found to be safe but NP001 was not shown to slow disease progression or improve breathing function. Post-hoc analysis (completed after the study has ended) has potentially identified a small subgroup of people from the trial that demonstrated slower declines in ALSFRS-R compared to placebo. Further research would be needed to confirm these findings. 

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?

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.