Treatment trials

AP-101 is a human monoclonal antibody that targets, and therefore seeks to reduce or eliminate, misfolded superoxide dismutase-1 (SOD1). This defective protein has been established as one of the causes of familial ALS. 

AL-S Pharma AG, a biotech company jointly founded and financed by Neurimmune and TVM Capital Life Science, has enrolled the first patient in its Phase 1 clinical trial assessing the safety and tolerability of AP-101. The multi-center, open-label, study is expected to recruit 18 participants from five clinical sites in Canada. Find out more about this trial at clinicaltrials.gov.

The experimental therapy has received orphan drug designation from the U.S. Food and Drug Administration, the European Medicines Agency (EMA) and Swissmedic for the treatment of ALS. 

CuATSM (Copper ATSM) is a candidate MND drug that is being investigated by the Collaborative Medicinal Development company for its effects of slowing down progression and improving respiratory and cognitive function. The drug is thought to work by delivering copper to cells where the cell's energy batteries, mitochondria, have been damaged, allowing for selective delivery of the drug (i.e. to only those cells that have been damaged).

The Phase 1 results were first announced in December 2018, showing that the treatment was safe and well-tolerated, with some beneficial effect observed. You can read more about the results in our blog article.

Find out more about this trial at clinicaltrials.gov

Phase 2/3 has begun recruiting in Australia in September 2019 to explore whether the drug is beneficial to people with MND, in a larger cohort of people.

Find out more about this trial at clinicaltrials.gov

Edaravone was originally developed by Mitsubishi Tanabe Pharma Corporation to treat acute ischemic stroke, however it was then tested in people with MND. One theory about why motor neurones die in MND is that they are affected by oxidative stress. Edaravone acts as a ‘free radical scavenger’ helping to reduce the effects of oxidative stress (as explained in a post on our research blog).

The first Phase 3 clinical trial of edaravone in MND found no overall benefit in people with MND, but showed an improvement in breathing function in a subgroup of people with an early form of the disease. Two studies have been conducted in this subgroup of patients. Results of the second study, announced at the 27th International Symposium on ALS/MND in 2016, revealed that after 24-week intervention patients showed some signs of beneficial effect. It has been estimated that approximately 7% of people with MND were eligible to take part in the clinical trials, showing improvement in only a small amount of people.

In early May 2017, edaravone (Radicava) was approved to treat MND by the FDA (Food and Drug Administration), the drug licensing authority in the USA. Read more about edaravone on our blog.

Edaravone is currently available in Japan, South Korea, the U.S, Canada, Switzerland, and China. In 2018, Mitsubishi Tanabe Pharma applied for consideration of edaravone as a treatment with the European Medicines Agency.

The Phase 3 clinical trial testing an oral suspension formulation of edaravone was launched in November 2019, but was paused in March 2020 due to the COVID-19 pandemic. The study, recruiting up to 150 adults with ALS (ages 18 to 75 years), is taking place at 65 clinical sites in the U.S., Canada, Europe, and Japan  (NCT04165824).

EH301 is a dietary supplement, combining pterostilbene and nicotinamide riboside, aiming to increase activity of sirtuins, proteins that are involved in multiple cellular processes known to go wrong in neurodegenerative disease and aging. 

In February 2019, a small Phase 1 trial reported results from 32 participants who were receiving 1,200mh of EH301 a day across four months. Most people taking EH301 significantly improved on ALSFRS-R, muscle strength, activity and mass, compared to people taking placebo, who were progressing at a 'normal rate'. Some adverse events were reported and 12 people withdrew from the study.

Phase 2 trial is now being planned to replicate the findings in a larger group of people. 

GM604 is a regulator peptide that monitors and corrects the nervous system. Prior research revealed that, when administered intravenously, it has neuroprotective effects in people with MND diseases. Genervon, the company behind the drug GM604, have already shown through Phase 1 and Phase 2 clinical trials that the drug is safe in people living with MND and Parkinson’s disease. Read more on our website.

The Phase 2A trial, taking place in the USA, recruited 12 patients with ALS, out of which 8 received the active agent and 4 received placebo. Results of this study reported in Genervon’s research article showed that there was no difference in ALSFRS-R ratings between patients receiving GM604 and those receiving placebo. The research article was posted on the public publishing platform F1000 in March 2017 and is currently awaiting peer-review.

No information on FDA approval of GM604 for ALS has been released, with the last updated information on the FDA website dating back to 2015.

Find out more about this trial at clinicaltrials.gov

Ibudilast, also known as MN-166, is an anti-inflammatory drug which is currently used to treat asthma, and tested for the treatment of MND and other neurodegenerative diseases (including Multiple Sclerosis) by Medicinova. It is thought to suppress inflammation, activate neuronal function and reduce the number of toxic glial (support) cells.

The Phase 2 randomised, placebo-controlled, double-blind clinical trial recruited 51 people with MND who were taking 60mg of ibudilast daily together with riluzole across 6 months, with a follow-up six month open-label phase. The treatment was shown to be safe and well-tolerated. Results of secondary outcome measures showed that, in some participants, the ALSFRS score didn’t decline. More detailed analyses revealed a connection between reduced disease progression while on ibudilast and higher survival rates after the treatment.

Ibudilast is currently being tested in a Phase 1/2 biomarker trial, which is trialling a higher dose (100mg) in 35 participants taken across 36 weeks, while tracking their progression using an MND biomarker [11C]-PBR28. This marker is a protein that is abundant in toxic glial cells and can be traced using imaging. Effectiveness of using this marker to track progression after treatment with ibudilast is the primary objective. Secondary objectives include ALSFRS , muscle strength and slow vital capacity scores.

Planning is now underway for a Phase 3 trial with 166 people with MND.

Masitinib inactivates a cellular enzyme called tyrosine kinase, which is believed to be involved in tissue inflammation. While inflammation of the central nervous system may not be a direct cause of MND, it is likely to play a role in the speed of disease progression. Reducing the activity of inflammatory cells in the brain may reduce the damage to motor neurones.

Phase 2/3 trial of this clinical trial examined the safety and effectiveness of masitinib in combination with riluzole in 394 people with MND, when taken for nearly a year. AB Science, the company behind masitinib, has recently published promising results, showing improved ALSFRS-R score when given 4.5mg/kg of masitinib per day. However, no benefit on overall survival was observed. A further clinical trial that will aim to confirm the previously-found results is planned to run through 2017-2018.

In April 2018, AB Science announced that masitinib was given a negative opinion for marketing authorisation by the European Medicines Agency (EMA). 

Phase 3 trial is now planning to test masitinib at two doses (4.5 and 6mg/kg/day) in combination with riluzole in 495 participants in Canada. The study should be completed in 2024. 

Neuralstem is a stem cell treatment that involves several injections of foetal-derived neural stem cells into the spinal cord of patients.

The latest Phase 2 study involved giving injections into the lower regions of the spinal cord, at increasing doses (number of cells), to help work out the optimum number of stem cells to give (these injections are given as a surgical procedure). Results from this study confirmed that the transplantation can be safely performed at high doses, to both lumbar (lower back) and cervical (neck) regions.

It is unknown whether another Phase 2/3 study will be conducted in the future. 

NP001 is being developed by Neuraltus Pharmaceuticals Inc. It acts on particular cells within the immune system in the bloodstream, which in turn influences inflammation within the brain and spinal cord. The study is focusing on people with MND who are also showing signs of an elevated immune response. By ‘damping down’ the immune system, the aim is to reduce the inflammation which damages motor neurones.

Results from the initial Phase 2 study, reported in late 2012, suggested that the treatment was safe, but did not significantly slow the progression of MND. The trial recruited 136 participants in centres across USA and at one centre in Canada. 

In April 2018, Neuraltus Pharmaceuticals Inc. announced that results form their follow-up Phase 2 clinical trial that tested the treatment in 138 people with MND with evidence of increased inflammatory activity in the blood (C-reactive protein). The study didn’t show slower progression of the disease or improved breathing function.

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.

Nuedexta was originally granted a marketing authorisation by the EMA in July 2013, but Avanir Pharmaceuticals Inc, the company who developed and manufacture the drug, did not take the further necessary steps to make it available in the UK, such as agreeing a price with the NHS under the Pharmaceutical Prices Regulation Scheme.

In February 2016, the European Medicines Agency (EMA) had withdrawn its marketing authorisation for Nuedexta in the EU.

The withdrawal has been made at the request of Avanir Pharmaceuticals Inc. Avanir have never made the drug available in Europe, and this decision means that it is not available to prescribe for patients in the EU. 

Because Nuedexta is a patented medicine, Avanir has the sole right to produce and distribute it; it will not be possible for another company to make it or for it to be imported into the EU – although it remains available in the USA

NurOwn reprogrammes bone marrow-derived stem cells into neurone-supporting cells. These are then transplanted back to the same patient so that they can secrete neutrotrophic factors to protect and promote growth of neurones. This study is run by Brainstorm-Cell Therapeutics.

Brainstorm’s  randomised, placebo-controlled Phase 2 trial of NurOwn in the USA looked at the safety and effectiveness of stem cell transplantation in 48 people. The injections were given into the spinal cord (intrathecally) and also into the muscle. Results announced in July 2016 revealed that NurOwn treatment was safe and well-tolerated. While not a primary objective of this trial phase, the study also showed beneficial effects of NurOwn as assessed by lower levels of inflammatory biomarkers in the cerebrospinal fluid (CSF).

Phase 3 trial has fully enrolled 200 participants across centres in the USA to investigate NurOwn's effectiveness, and treatment is now underway. Results are expected by the end of 2020.

Find out more about this trial at clinicaltrials.gov

Prosetin is an oral, brain penetrant, small molecule shown in multiple laboratory models of ALS to block MAP4K, a specific group of protein kinases that several leading academic researchers & drug companies have identified as a key player in ALS/MND.

While a Phase 1 clinical trial investigating Prosetin was due to start the summer of 2020, the COVID-19 pandemic delayed previously ongoing preclinical and clinical research. However, Project ALS’ goal is to initiate human clinical studies by the end of 2020.

In August 2020, the U.S. Food and Drug Administration has granted Prosetin orphan drug designation for the treatment of amyotrophic lateral sclerosis (ALS). While Prosetin’s orphan status will not change the timing or viability of clinical trials, it does make it eligible for research grants specific to orphan drugs. These could support more rapid and robust efforts to develop Prosetin as a clinically useful compound. It also allows Prosetin’s developers to seek additional FDA help and guidance when designing clinical trials.

A research paper detailing Prosetin’s development and mechanisms of action was published last year, in the journal Cell Chemical Biology.

Tirasemtiv is a muscle activator that increases force (contraction) and power of skeletal muscles and therefore delays muscle fatigue. Instead of aiming to slow down progression of MND, the aim of this drug treatment is to increase quality of life by increasing muscular strength. The drug is being developed by Cytokinetics.

A Phase 3 clinical trial (known as VITALITY-ALS) recruited 600 people with MND in the USA, Canada and Europe (including the UK). The trial tested the effectiveness of different doses of Tirasemtiv on breathing function over a period of 48 weeks. The trial was designed to try and reduce the side effects of the drug experienced in previous studies.

In November 2017, Cytokinetics announced that tirasemtiv failed to meet its primary and secondary endpoints in their Phase 3 clinical trial. Read the press release here.

A new version of the drug, called Reldesemtiv, is being tested in a Phase 2 trial (known as FORTITUDE-ALS) which recruited 458 people with MND worldwide. Results from this trial are now expected.