On Tuesday, Innate Immunotherapeutics released a report outlining the first set of results from their Phase 2b trial on the use of their compound, MIS416, in people with secondary progressive multiple sclerosis (SPMS).  Unfortunately, these findings have shown that there was no statistically significant benefits received for the people on the trial who received the treatment, compared to those who were in the placebo group.

In the trial, the researchers assessed the following factors:

    • Neuromuscular function – including upper extremity function and strength, walking speed and distance, cognitive processing and visual acuity
    • Individual reported outcomes – including fatigue, quality of life and pain
    • EDSS
    • Brain volume change
    • Lesion number and volume

Across each of these different factors, the initial reporting has shown that MIS416 did not result in any statistically significant benefits.  Innate have said that they will be conducting further analysis on the results to see whether or not there was a specific group of people in the study that did respond positively to the treatment.  If there is, they will then be trying to work out what factors caused these people to benefit, while others did not.

It is important to note that more than a quarter of the original participants in the MIS416 group (as well as 13% of the placebo group) did not complete the trial.  This was due to either an adverse event, not complying with the protocol or purely deciding that they didn’t want to continue.  It is my understanding that the results that were available from these participants were included in this first analysis that has been presented.

That summarises the results that have been released so far, but I thought it might be worthwhile to share some of my own personal thoughts on this news.  It is worth mentioning again that we did some promotion of the MIS416 trial in late 2015.  As part of this, I did meet a number of the team that were involved in the trial and were hugely impressed by their commitment, dedication and complete desire to help people living with multiple sclerosis.  For these reasons, I am (on a personal level) very disappointed for all involved at this result.  Further, this disappointment is massively compounded by what it means for people living with secondary progressive MS.  Despite this disclosure, none of what I am about to say is influenced by these feelings.

The first point that I would like to make is that I would love to see the actual data that has been generated from the trial.  It isn’t until this point that I can really make any definitive statements about the outcomes of the study.  However, I don’t believe we have reached the point where we should give up hope on MIS416.

In some ways, this reminds me of the recent anti-LINGO trial results – positive early phase findings not being replicated in a larger study.  In this case, Biogen have since determined that some aspects of the trial design need to be altered for a real test of the treatment potential.  This may not be the situation for MIS416, but it warrants investigation.

Secondly, I think it will be interesting to see what happens when the comparison of results from only the people who completed the full trial are analysed.  I do wonder whether the quite large drop-out rate from the treatment group has shifted the results slightly, though again, I need to see the actual data before commenting on this.  Obviously, the reasons behind the drop-out need to be better understood and whether any serious safety concerns exist.  Currently, it is suggested that it was mostly flu-like symptoms, which have been experienced by earlier trial participants across the first few treatment doses.

Lastly, the question must be asked about how the significant benefits reported from earlier trial participants were not replicated in this study.  Is it purely a placebo effect?  This is certainly possible and is the exact reason why placebo controls are necessary.  If this is the case, I would expect to see a positive response from both groups in the data (e.g. both reported an improvement in fatigue).  This is again something that I will be able to comment on in more detail once the full results become available.

As of today, I’m sure this result is very disappointing news for the MS community.  However, I hope that after that initial frustration subsides, there is still some positivity that can come out of this work and we will continue to see how it develops once the full analysis is available.

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