Has there been any hint that Amilioride, Prozac or Riluzole will be fast tracked, if there is evidence it works in MS-SMART,...Not that I've heard. Is this the difference between academic studies and pharma led studies or pro-active Americans verses lazy bummed Brits.
However, based on what happened with Simvastatin. I think we can be sure of slow track for academic-led stuff:-(The phase II happened in 2010 phase III yet to be funded and by the time it will complete pharma will have found something so that it will never be licensed:-(
As for MS-SPRINT I suspect they will still need to do a phase III if this trial is positive. So access may not happen soon.
MS -SMART is a UK based trial originally intended to test Ibudilast, Amiloride and Riluzole in Secondary Progressive MS.
However, the UK missed out because they could not get a drug supply as I guess it was being funnelled into MS-SPRINT in the USA
I first heard about Ibudilast when someone who had been trawling the patent data base brought this to my attention and wanted us to do some EAE work.
I first came across these, because phosphodiesterase 4 inhibitors were reported to block tumor necrosis factor (TNF) and not surprisingly it was reported that they block EAE, because at the time tumour necrosis factor was considered to be bad for MS. However...
Does this ring any alarm bells?
You may know that in contrast to EAE when you block TNF then two MS trials in relapsing MS were stopped because of apparent worsening and it seems that anti-TNF can exacerbate MS. Therefore blocking TNF=bad
Now there a loads of different PDE4 inhibitors, another one was called rolipram.
This too could block EAE if used at high doses and was also reported to block TNF.
However, this could make some symptoms of disease worse in mice, which we reported in 2002 and importantly
Clinical trial in MS was stopped because it was apparently making MS worse.
Now you can say that this is yet another example of EAE failing, but rather than it making EAE worse, or better as was originally shown when TNF=Bad, at doses equivalent to those used in humans, rolipram and ibudilast etc actually did nothing and had no effect on relapsing disease. Showing us that unless we read the animal data properly, we may get the wrong idea.
Thus animals in contrast, what many think actually, predicted what was found with Ibudilast in humans ...in the first clinical trial there no effect on relapsing disease....No worsening Phew.
So maybe not all PDE 4 inhibitors are created equal.
(Were the anti-TNF and rolipram trials flukes?.....the occurence in people with arthritis treated with anti-TNF says there is something in it and also that not everyone treated with anti-TNF gets MS so there is something selective in this.
I suspect TNF= good and TNF=bad also but it is context dependent and timing may be critical is what happens when.
However the ibudilast trial was large and had nearly 300 hundred people in the trial and so if there was a problem you would hope it would have been seen.