Clinical trials: Highlights from Glasgow

This blog is part of the ‘Highlights from Glasgow’ collection of articles, where you can read about the content of some of the talks and posters presented at the 29th International Symposium on ALS/MND.

In the Clinical trials and trial design (4B) session we heard from two speakers looking at ways to improve current design of clinical trials. In his plenary talk, Mahesh Parmar (C20) provided his perspective on the necessity of changes from his experience working on cancer trials, highlighting that any efforts to improve clinical trials should be focused on Phase 3 where the most money and time is spent. One solution that stuck with a lot of clinicians attending Prof Parmar’s talk was the design used in the STAMPEDE trial, a large clinical trial assessing effectiveness of new treatments for people affected by prostate cancer, which has been running since 2005. The innovation of this approach is the ongoing protocol that allows to test multiple treatments within the same established clinical trial, allowing new drug candidates to be tested (relatively) straight away, avoiding the creation of a brand new clinical trial. This design improves efficacy of testing new treatments, systematic approach to testing, and access to a large pool of participants who could take part in multiple treatment trials over time.

Brian Dickie, the Director of Research Development at the MND Association said: “Prof Parmar’s presentation generated a lot of interest amongst clinicians who are regularly involved in MND trials and there was a strong feeling that this is the direction that we need to be taking with MND as it could increase the efficiency and reduce the cost. That said, it will take a while to put the building blocks in place and we certainly wouldn’t want to hold up trials that are already in advances stages of planning, so I would expect to see a gradual introduction of changes to trials design over the coming years.”

You can learn more about the multi-arm multi-stage trial design from Prof Parmar here.

Read More »

MND Research in 2012

Word cloud from our 2012 blog posts. Created from wordle.net
Word cloud from our 2012 blog posts. Created from wordle.ne

At this time of year, it’s always good to look back on the previous year to see just how far we’ve really come. We’re pleased to say that 2012 was full of progress being made in the world of MND research and we hope that the speed and number of exciting findings being announced continues at this pace in 2013.

In 2012, 1,466 scientific papers were published in MND, which is 200 more than the previous year, demonstrating the energy and speed at which progress is being made.

Twitter: If you follow us on Twitter, then we’d like to take this opportunity to thank you for your re-tweets and mentions throughout 2012 to help raise awareness of MND and to keep your friends and family up-to-date with our exciting news. We managed to double our followers in 2012 because of your continued support!

News stories:

We wrote over 30 blog articles in 2012 to take you behind the scenes of MND research. These were viewed over 36,000 times with visitors coming from 126 countries. Here’s an over of a few of the findings we wrote about in 2012:

Clinical trials

At the start of the year, we heard some exciting news that a drug called Cogane produced some encouraging results in an MND Association funded study. A few weeks ago we heard an update that the drug company who owns Cogane called Phytopharm are moving toward a clinical trial and are currently securing funding and support for this. This could  take a number of months before final plans are made but it’s positive to see that MND Association funding has led to this exciting development!

It was also positive to hear some encouraging NP001 clinical trial results for MND, which is leading toward a larger Phase III study to test the effectiveness of this drug in MND in America this year.

Angiogenin findings advance our understanding of MND

In June, we heard that Irish Angiogenin research lead to promising results. One finding was related to a new biological finding of the vital role that angiogenin plays and the second expands on this work and led to the testing of angiogenin in mice that model MND. Later on in the year, we also heard how University of Bath research showed how angiogenin affects motor neurone survival.

New genes

We also heard about some exciting findings in understanding how genes can influence survival and cause MND for some people. In July, Profilin1 was identified as a cause of MND. In our blog, we explained that Profilin 1 has a role in holding the shape of the cell through the cells scaffolding – called the cytoskeleton. We then heard about another gene called EPHA4 which influences survival in MND.

EPHA4 also plays a role in the cytoskeleton which means that researchers can explore this pathway in more detail as it, in conjunction with the Profilin 1 finding, suggests that this guidance/growth system of motor neurones may play an important role in the development of MND.

Advancing our understanding of C9ORF72

Since the discovery that a repeat expansion in the C9ORF72 can cause MND in 2011, researchers have been working to understand more about it. We announced that we would be funding a new Fellowship which aims to explore how C9ORF72 causes MND using our DNA bank samples. Very late in 2012, we also heard that MND Association funded researchers had identified the structure of C9ORF72 repeat, which looks (with some artistic license granted) surprisingly like a Battenberg cake! It will be interesting to see this field of research continue to yield exciting developments over 2013 and beyond.

TDP-43 research in yeast

TDP-43 was identified as a cause of inherited MND for approximately 4-5% of people with a positive family history of the disease in 2008. Since then, researchers have been working to identify how this gene can cause MND and how this system could be targetted to develop a new treatment for MND. In November, we wrote about a study which marked the first steps in the identification of a treatment that can target TDP-43, which is found to clump together in over 90% of cases of MND. Using a novel yeast model, the research group identified that they could reduce the toxic effect of TDP-43 as a potential therapy for MND.

As this is the beginning of the story of TDP-43 specific treatments for MND, it will inevitably be a long journey to answer these questions and to bring treatments to the doctor’s prescription pad. However, it is positive that this research is moving forward and that we are moving in the right direction.

Symposium 2012

One of the highlights from our year is always our International Symposium on ALS/MND. It’s an accumulation of over a year’s worth of work for our Research Development Team and is a fantastic platform that really demonstrates how far research has come in a year.

For our 2012 International Symposium on ALS/MND, we received 419 high quality overviews of research (called abstracts) from across the globe, totaling 172,581 words!

Over 900 researchers, clinicians and healthcare professionals from 30 countries attended our sympsoium in Chicago USA in 2012 to hear 86 platform presentations and to see over 300 poster presentations.

To keep you up to date with news from the symposium, delegates used the Twitter hashtag #alssymp. In total, 950 tweets were sent using this hashtag!

We also blogged live from the symposium to bring you news as it broke, we summarised these findings in our Symposium highlights 2012. There’s still time to share your thoughts about our symposium blogging to assist us with plans for 2013! To take part, please visit www.surveymonkey.com/s/alssymp.  We will be closing this survey on 31 January.

Thank you!

For following news from the ever changing world of MND research on the MND Association’ research blog, we would like to thank you! We hope you enjoy reading our blog posts in 2013 and help us to raise awareness of MND and the pace of research by sharing our news stories with your friends and family!

The clinical trials session

A very much ‘must report on’ session of the 23rd International Symposium on ALS/MND was the clinical trials and trial design session. There are many reasons that make this an interesting session – perhaps the most eagerly anticipated were the presentations on the NP001 study and the results of the stem cell safety trial:

NP001 update

We reported on the blog on 1 November the results of the NP001 study, and these findings were confirmed today by Dr Bob Miller from Forbes Norris Centre in California USA. The trial showed that intra-venous administration of NP001 was found to be generally safe and well tolerated, with a modest clinical benefit seen in the high dose (2mg/kg) group.

As previously reported in their press release, ‘post-hoc analysis’ (meaning literally after the event), showed that some patients in the higher dose group did not have any change of a scale that measures the functional capabilities of people with MND called the ALS-functional rating scale (ALSFRS) over the course of the study. Historical controls were used in the post-hoc analysis – the first time that the US Food and Drugs Administration (FDA) had allowed them to do this.

The room was packed and there were five people queuing to ask questions about this talk. Questions were asked about the use of historical controls; the possibility that patients would identify that they were in the treatment group due to the presence of a ‘burning feeling’ at the injection site; and about other forms or ways of taking NP001. On the last of these points, a question about the chemical structures of NP001 and WF10 went unanswered.

But Dr Miller was categoric about different ways of taking NP001. “Taking NP001 in any other route [than intra-venously] is unsafe and unproductive”.

Results of stem cell safety trial

The first regulatory body (FDA) approved phase I safety trial of a stem cell treatment for MND, conducted in America, is now complete. Dr Johnathan Glass from Emory ALS Center, Georgia USA presented the results of this study.

In the last 5-10 years there has been a huge amount of interest from MND researchers, clinicians and patients alike about the possibility and potential for using stem cells to treat MND. More information about what stem cells are and how they might help is available on the MND Association’s website.

As for any other drug or potentially beneficial intervention, the first part of the assessment should always be to obtain a robust and objective measure on whether such a treatment is safe, and this is what the NeuralStem study was designed to find out.

A team of highly trained specialists, in close consultation with the FDA, designed a study to look at the safety of giving an injection of stem cells directly into the spinal cord of people with MND. Eighteen surgeries were performed on fifteen patients – three of these patients volunteered to have two surgeries (two injections).

The first three people with MND recruited into the study received a single injection of stem cells on one side of the bottom (lumbar) of the spinal cord. The next three received injections on both sides of the lumbar spinal cord. These first six patients were at an advanced stage of MND, where they were unable to walk.

The next six patients, who were able to walk, received injections at one or both sides of the lumbar spinal cord. The last three patients received a single injection higher up the spinal cord (cervical) and finally, the three patients able to walk who received a single lumbar injection underwent a second surgery to receive a single cervical injection.

The results from the first six patients has already been published in a scientific paper:

Stem Cells 2012 30(6) 1144 – 51

Dr Glass concluded that the procedure is well tolerated and safe and that there is no indication that the surgery accelerates the progression of the disease. The next phase of the study, giving injections into the cervical spinal cord at increasing doses (numbers of cells) is funded and is awaiting FDA approval.

Our International Symposium website news stories:

International Symposium closes in Chicago

International Symposium focuses on clinical trials

International Symposium focuses on carer and family support

International Symposium begins in Chicago

Researchers unite at our International Symposium on MND

After you’ve finished reading the symposium articles that interest you, we’d be grateful if you could spare a few minutes to fill in our short online survey on our symposium reporting. Your comments really are useful and allow us to continually improve our symposium reporting. surveymonkey.com/s/alssymp 

Encouraging NP001 clinical trial results for MND

Promising results from a Phase II clinical trial for a drug called NP001 have been announced by the biopharmaceutical company Neuraltus.

The trial, conducted in America, suggested that NP001 is safe, well tolerated and could be beneficial for MND.

Following these encouraging results, Neuraltus plan to begin a larger, Phase III trial of NP001 in the second half of 2013. As the Phase III trial is still being planned, we do not have details on American recruitment centres, nor what the eligibility criteria will be.

The trial
The Phase II clinical trial for NP001 was rigorously controlled. This means that it was randomised, double-blinded and placebo controlled. These are important factors in controlling possible bias. We have more information on why these factors are important on our website.

The trial included 136 people living with MND in America across multiple centres.

Participants were randomised into three groups to receive an intravenous infusion of either high dose NP001, low dose NP001 or placebo (inactive substance) treatment for six months. They were then followed for an additional six months. Approximately 45 people were used in each treatment arm.

The results
Results suggest that the treatment was safe and well tolerated. Promising signs of effectiveness were also identified, but were not statistically significant to draw firm conclusions as to whether the treatment could be effective for MND.

The trial organisers state in their press release that 27% of people taking the high-dose NP001 did not progress during the trial period. It’s important to treat these results with a certain degree of caution, as approximately 10% of people taking the inactive placebo also did not progress during the same period as measured by changes in the functional rating scale.

The results provide enough evidence to warrant a larger scale trial to investigate this treatment further.

This finding also importantly identifies the optimum dose that should be used in this larger-scale clinical trial, as their results suggest that a higher dose could be more likely to yield a beneficial effect than the lower dose.

Finding out the optimal dose is an important part of Phase II clinical trials to ‘fine tune’ the details to provide the treatment with the best chances of demonstrating its success at Phase III.

Importance of sharing results via peer-review
These results will need to be published in a peer-reviewed scientific journal. Peer review is an important process to determine whether findings are valid and that appropriate standards have been used in the study. Once published, these findings will also be used by the scientific community to add to their knowledge.

Importance of Phase III planned for 2013
The promising results identified in Phase II will need to be confirmed in the Phase III trial planned for the second half of 2013.

Leading UK clinical trial researcher, Prof Nigel Leigh said, “A larger Phase III randomised placebo-controlled trial is required before we can be confident that these positive trends are consistent and clinically significant.”

Dr Brian Dickie, the MND Association’s Director of Research continues, “We welcome Neuraltus’ plan to initiate a Phase III trial to determine whether NP001 is beneficial for people living with MND.”

Discussing results at the International Symposium on ALS/MND
Results from the Phase II NP001 trial will be discussed in more detail at the 23rd International Symposium on ALS/MND, to be held on 5-7 December 2012.

The symposium, organised by the MND Association provides a platform for researchers, clinicians and healthcare professionals to discuss the latest developments in research and care, including discussing results from recent clinical drug trials.

We will be reporting live from the symposium via our research blog. To ensure you have daily updates from the symposium, please sign up to our automatic email alerts on the right hand side of the blog.

References:
Our news release
Neuraltus’ press release
International Symposium on ALS/MND
Brian’s NP001 blog article

Clinical trial low down, down under

“After a time where patients and sponsors of trials alike had become disheartened about the lack of positive clinical trials, it is exciting to see so many positives, including the recently approved Neudexta, and the dexpramipexole study”, commented Professor Robert Miller from the Forbes Norris ALS/MDA centre in San Francisco opening the discussions on clinical trials.

Designing a good trial
As MND is a rare disease clinical trials are notoriously difficult to design in order to ensure that they have meaningful results. Designing better and quicker clinical trials will aid us to find the answers as to whether a treatment is beneficial or not, without losing the significance of a study. It is therefore important that clinical trial designers share their methods with one another. In the first presentation of this session Prof Miller gave us some pointers on how this may be done, looking at every aspect from designing shorter trials with fewer participants, to how an effect is measured.

The next few talks were then dedicated to discussing results from recent clinical trials:

Lithium
Prof Leonard van den Berg, from University of Utrecht, The Netherlands presented the results from the Netherlands lithium clinical trial. Unfortunately, although they found the treatment to be safe, no beneficial effects were seen. The results from the UK clinical trial of Lithium Carbonate, which was designed in a different way with more participants will be published early 2012.

Memantine
Dr Ming Chan from University of Alberta, Canada discussed the results of the recent memantine pilot trial for MND. This trial treatment was administered via tablets. Twenty four people took part in this study and were randomly divided into one of three groups who would receive either: high dose memantine; low dose memantine; or a placebo (dummy) drug. Overall, the trial results suggested that the treatment is safe, and at the higher dose a larger, multi-centre clinical trial for memantine may be warranted.

Nogo-A (GSK1223249)
Dr Pierre-Francois Pradat from the Centre for MND in Paris, France presented the very hot-off-the-press results of the Nogo A trial – a drug developed by the pharmaceutical company GlaxoSmithKline, that is delivered directly into the blood stream via an intravenous (IV) drip. This was a Phase I ‘first in man’ study, given to people with MND first. This is different to other Phase I clinical trials, as healthy volunteers are more commonly used for this stage of trial.

The aim of this study was to ensure that the treatment was safe and well tolerated in people with MND. Dr Pradat discussed that the drug was found to enter the body effectively. The investigators saw trends (ie they are not statistically sure) of benefits in slower decline of respiratory function, of a scale that measures the functional capabilities of people with MND called the ALS-functional rating scale (ALSFRS) and muscle strength. Tentative plans are underway for a larger clinical trial next year.

NP001
NP001 is a drug developed by Neuraltus Pharmaceuticals.  This trial treatment is administered directly into the bloodstream via an intravenous (IV) drip.

At present a Phase II clinical trial for NP001 is underway in the USA and we acknowledge that a lot of people living with MND are interested in hearing more about the status of this trial. This talk however, focused on the Phase I trial to tell us the effects of NP001 on potential markers of disease progression in MND (known as biomarkers), identified through the earlier Phase I trial. We can therefore not comment on the current status of the Phase II trial in this blog article.

As discussed by Prof Miller, from Forbes Norris ALS/MDA Research Center in San Francisco USA and principle investigator to the trial, it is thought that NP001 may be beneficial as the levels of proteins which are increased as a result of an inflammation response in MND are decreased by the drug. They also concluded that the levels of these inflammatory response proteins can be related to the rate of progression for people with MND and could potentially be used as a marker.

Read our official press release from day three of the symposium.

NP001: Dr Brian Dickie’s comments…

I’m sure many of you who follow our blog have also been following the discussion on our forum about the Neuraltus trial for a drug called NP001. First of all, thanks to ‘Matt J’ for initially raising this issue on our forum. It highlights the power of the forums in facilitating information spread and getting new news out to the community quickly. I also appreciate his initial trepidation in posting as it illustrates some of the ‘messier’ aspects of forum-based communication, such as the difficulty in following threads and in separating the ‘wheat’ from the ‘chaff ‘in terms of evidence.

Secondly, the disclaimer. It is not the Association’s role to provide medical advice. We’re not clinicians. Where possible, we’ll try to present the facts as we understand them, throwing in a few assumptions or speculation where it’s unavoidable.

This relates to a third point. NP001 is a North American trial. If it were a UK trial we would undoubtedly know much more about it and be in closer contact with the company. The downside of a closer relationship is that Patient Organisations have to sign a Confidentiality Disclosure Agreement (CDA) with the company, which restricts the amount of information that can be disseminated. I suspect this is probably the case for some of our North American counterparts. So this means that while our information is more limited that we would like, we are at least in a position to communicate something.

At the moment we simply don’t know whether NP001 is working or not. I appreciate the frustration that statement will generate, but there are some issues that have to be discounted before any conclusions can start to be drawn and these form a large part of the rest of this blog.

I’m going to spend some time on the underlying biology of MND as it is highly relevant to this issue. I’ve tried to make it accessible and not cut too many corners, but given the different degrees of knowledge among our readership, it can be difficult to pitch at the right level, so I hope it is understandable to all, but does not come across as simplistic or even patronising to some. That is certainly not my intention. Neuroscience and Immunology are arguably the two most complex subjects in medical science and drug trial design in MND is a ‘dark art’ in itself. I can’t claim to be speaking with authority on every aspect.

How do we think NP001 works?

From what we know, NP001 affects the activity of modified white blood cells called macrophages, which are an important part of the immune system and, among other roles, are involved in inflammation. Macrophage activity and proliferation increases alongside disease progression in MND. Neuraltus are seeking to prove that reducing macrophage activation with NP001 has a beneficial effect on disease progression. They have not stated clearly how they expect lower numbers of activated macrophages to achieve this. However, the mechanism probably involves cells called microglia.

Microglia are macrophages that have infiltrated the central nervous system (CNS). Unlike the rest of the body, the CNS does not have an immune system, so it relies on microglia as a key part of the ‘defence system’ here. Previous research, mainly based on SOD1 mouse models of MND, has shown that microglia play an important role in influencing the progression of MND but they do not appear to be involved in triggering the disease in the first place. Instead, they form part of a specialised inflammatory response which aggravates the initial problem. We know that MND is not primarily an immune system disorder because treatments like immunoglobulin, which impact significantly to depress immune system, responses, have no effect on the disease.  Controlling microglia activity more selectively is a valid strategy which may help slow the progression of MND but as it is probably addressing a secondary pathology rather than the primary pathology, the strategy is aimed at slowing disease progression rather than stopping or reversing it.  

Neuraltus may believe that, because macrophages give rise to microglia, a reduction in macrophage activity and numbers in the blood will be paralleled by a reduction in microglia activity in the CNS. However, macrophages also produce lots of chemical messengers that act to promote inflammation in general – within the CNS it’s microglia that respond to these messages. It may be that Neuraltus scientists are working on the theory that reducing the production of these inflammatory messengers may limit inflammation in the central nervous system, at least in part through decreased stimulation of microglia. Whatever the precise mechanism, they intend to measure macrophage levels and activity as a ‘biomarker’, to demonstrate that the drug is at least hitting its intended target.

Could NP001 have an instant effect?

One of the members of our forum commented that the reported changes within a few hours were surely too fast to be drug related? I’d tend to agree.

The CNS has an amazing capacity for compensation – this is particularly the case in Parkinson’s disease, where up to 80% of the vulnerable neurones have degenerated before the first appearance of symptoms. Even in MND it’s estimated that by the time a muscle group is affected, it will already have lost up to 50% of its neuronal connections.   

The compensation occurs by a process called collateral innervation (or compensatory innervation). In a nutshell, if a motor neurone cell dies back from its target muscle, the muscle releases neurotrophic factors that attract a neighbouring, healthier, neurone to literally ‘sprout’ a new connection, but this will take place over a longer timecourse than a few hours. A really good example of this process in action comes from looking at polio patients.

Polio is caused by a virus (poliovirus) that wipes out a large number of motor neurones in an instant, causing paralysis.  However, people can often recover partial or complete function, caused by the compensatory innervation by the surviving motor neurones. This process takes a long time, as many people who contracted the virus in childhood in the 1940s/50s and spent many months, even longer, in ‘iron lungs’, will testify. 

So, the first point is the rapidly reported changes are too rapid. This doesn’t discount, for example, a drug effect directly on the muscles rather than the nerves themselves, perhaps reducing peripheral inflammation, or some other metabolic ‘pick me up’. However, as outlined above, that doesn’t appear to be the mechanism of action of NP001 and certainly not the mechanism by which restoration of function is most likely to occur. 

It’s important to remember that in MND, compensatory innervation is occurring even after the disease symptoms appear. This can explain why any individual can have a plateau phase or even slight transient improvements in muscle function.  So, the second point is that loss of muscle function in any single individual cannot be viewed simply as a straight line, a constant decline.

For a moment, let’s assume that the drug has a quick acting effect. The question that follows is whether it is a short-term or a long-term effect? It could be transient.

The only way of working that out is through continuing the trial for a longer period. I am less familiar with FDA regulations, but the NP001 trial will have an independent Data Monitoring Committee, which will confidentially review the trial data at various timepoints, with predefined ‘stopping rules’. This is primarily carried out for safety, to ensure the drug is not making things worse. However, such committees are also able to flag up any significant positive deviations due to the drug, but they would need to be convinced that this was not down to the inherent variation in disease progression within and between individuals (some of which has already been discussed) and/or a statistical ‘glitch’ due to the low power of the study (by that I mean not enough participants). I completely understand the need for answers as quickly as possible – this is a disease where time is very much a luxury. It makes my third point that more difficult to state: basically, the trial needs to run its course and calls for the discontinuation of the current NP001 trial are premature.

If the results from the current Phase II trial are outstandingly positive, it is possible that the company could attempt to apply for licensing straight away. In this case, their first port of call would be the FDA in America, which has already granted NP001 ‘fast track’ status. This is a commitment to dealing with the licensing paperwork quickly but is not an endorsement of efficacy. ‘Fast tracking’ does not automatically mean that a Phase III trial will not be necessary – if the data from the Phase II trial are encouraging but not significant enough to be conclusive, then the company would need to proceed to Phase III.

The FDA has no influence over UK licensing. We will investigate whether there is anything we can do to hurry the European licensing authority along in the event that the Phase II trial or a future Phase III trial produces positive results. Ultimately though, while we may be able to try and ‘pull’ things along from this end, it is up to the company to ‘push’ by making the application in the first place.

As has been mentioned elsewhere, information on NP001 will be presented at this year’s International Symposium in Sydney (30 November – 2 December 2011). I believe that the Phase I study data, which was also performed in MND patients, will be presented. That should at least tell us whether any rapid effects were seen in that preliminary study.

This leads to a point which I approach with a great deal of trepidation, but it needs to be raised. With all the discussion on NP001, there hasn’t been much said about the placebo effect but it does offer one explanation for the improvements claimed by some of the participants. I’ll talk firstly from personal experience of 15 years in working in the MND field. In virtually every major trial I can recall (myotrophin, xaliproden, creatine, BDNF, pentoxiffyline, etc) there are invariably a small number of claims of improvements which have unfortunately not been borne out by the trial results. Additionally, in every clinical trial, participants in the placebo group also experience ‘adverse events’ that could be perceived as drug side effects, but are unrelated.

Let me give you an example, which was presented at the symposium several years ago. A pilot randomized, placebo-controlled trial of creatine was performed. Participants were assessed in a variety of ways, including direct objective measures of muscle strength (maximum voluntary isometric contraction). Participants were assessed before their first dose (baseline) then at 1,2,3 weeks, 4 months and 9 months.  When the results were analysed, it showed that those on the creatine arm showed an improvement in muscle strength in the first week and no overall decline from baseline in the first three weeks. However, those on the placebo also showed a subtle increase in the first week and no overall decline from baseline over the first three weeks. At the 4-month timepoint there was a marked decline in both groups, which was much more pronounced at the 9-month timepoint. As we know, the initial excitement of creatine was not supported in larger, more comprehensive trials. Basically, this illustrates another reason why the NP001 trial needs to be performed for longer.

 What about WF-10?

A colleague with extensive experience in drug discovery in the pharmaceutical industry has trawled though numerous patents to try and work out whether WF-10 and NP001 are one and the same, but were unable to reach that conclusion. Patents are legal, not scientific documents, so the scientific detail is often substandard or absent. The proposed mechanisms are certainly similar and the main active component is probably the same but the chemical formulation of NP001 is not available (if anyone can find it, please let me know). On the evidence available, we suspect that the two are different and we can speculate that NP001 is possibly a ‘souped-up’ version of WF-10 – either an improved formulation or a combination of more than one drug acting on inflammation /immunity. Either way, the bottom line is that if NP001 is ineffective, WF-10 probably will be too.

Some of our forum members have asked if we could organise a trial of WF-10. As you will appreciate from the previous paragraphs, there is no such thing as a quick or simple trial so the NP001 results would be known a long time before a WF-10 trial could come to fruition. Besides this, there is no reliable laboratory or clinical evidence to support the use of WF-10 in MND. While Nuvo Research and its subsidiaries have researched WF-10 in relation to a number of other macrophage-associated diseases, they have only hypothesised that it may be helpful in MND. Outside of a mention in a patent document of its short-term administration in two MND patients many years ago, they have not actually studied its effects in neurodegenerative disease.  

As you know, ALS Untangled is going to look into the evidence for WF-10 and have told us it’s next on their list. I don’t think we can pin them down to a date, as each review depends on the quality, quantity and availability of information, but they have at least moved the likely date forward from end of the year. The clinicians who are members of ALS Untangled are the best qualified to review the data and we will forward anything we find to them – including relevant information that our forum members may discover. I know that their objectivity has been questioned, given that some may be involved in the NP001 trial, but any such concerns are unfounded.

Some of you have asked about access to WF10 on a compassionate use basis.  As neither of these drugs is licensed for use in any condition in the UK, the situation is far more complex than for a licensed drug like lithium, which can more simply be prescribed ‘off label’ due to its use in treating other CNS-related conditions for the past 40 years.

The decision to proceed with compassionate use rests entirely with clinicians. In theory, consultants can prescribe unlicensed drugs like WF-10 to a particular individual (or ‘named patient’), provided that they and the NHS Trust they work for are prepared to accept complete responsibility for the consequences. I n the case of WF-10 they would need to do this for a drug that they have no previous experience of and for which there is not yet any evidence of efficacy in MND. Even if a consultant did decide to prescribe WF-10, the Medicines and Healthcare Regulatory Agency (MHRA), which oversees the licensing of medicines in the UK, must still grant permission for the unlicensed drug to be imported into the country for that particular patient. In order to give this permission, the MHRA will need to be satisfied that the patient has a ‘special need’ for the unlicensed drug. Although everyone with MND has a desperate need for effective treatments, the MHRA definition of ‘special need’ means a need that is relatively unique to that individual, such as an allergy to an ingredient in the equivalent licensed drug.

I hope the information provided is helpful.  These are exciting times in MND research – new knowledge about the disease is emerging fast and we are seeing an increasing number of trials emerging around the world – but due to the complexity of MND, these trials move at a speed that appears ‘glacial’ and NP001 is no exception. Only time can tell if we are looking at a genuine ray of hope and not another false dawn.