Last year we there was a buzz at ECTRIMS about ocrelizumab and this year it may well be Siponimod and its influence on secondary progressive MS. This is to be presented at the late breaking session at ECTRIMS 2016.
Is this a game changer?
The disruptor for MS pharma, is fingolimod coming-off patent in 2019. With the development of generics the price tumbles (except that MS pharma control a number of generic companies 🙂
However, does the success of siponimod mean that people in power are happy that fingolimod failed in PPMS?
Had it been a success could they have protected the PPMS market, whilst the RRMS fell to generic competitors?
As fingo is second line surely Sipo will get a first line label now. This is because the climate has changed since fingo was approved and got a second line label (It was expensive and had side effects), as alemtuzumab exceeds this on price and side-effects but that has a first line label (in UK).
Siponimod has succeeded in relapsing MS in early trials just like fingo other all other fingo me too’s and now with some success in SPMS. Why go for fingo when you could have sipo to cover RR and SP bases?
Was this the master plan?
However, will this be a game changer?
First we have to know is whether it is really progression that is being targeted or has the trial been loaded with relapsing people with SPMS? If I was designing a trial I would load it with people with lower levels of EDSS and have as many gadolinium enhancing subjects in the mix.
We know that relapsing MS/MRI activity contributes to damage and we know that this responses to Spingosine-1-phosphate modulators?
We will have to wait and see the data. It will be the first question everyone asks but I suspect that “the data is still being analysed”.
Answers to this may help define the battle ground with ocrelizumab.
Is Siponimod the first drug to have an effect on progressive MS? However, will we have deja vu and just as oral cladribine stumbled at the last hurdle to be beaten by Fingolimod, will siponimod be pipped or pip ocrelizumab to the final progressive hurdle?
Will the regulators buy the idea that ocrelizumab was active for all of progression, rather than just working in active (MRI positive relapsing) progression? I suspect the data has been collected in such a way that it will be impossible to answer as there were probably not enough scans to work out if lesions occurred after the initial negative scans. I personally think this will be a tough ask, but can the regulators be hood-winked?
Importantly will the cancers that popped up (nine verses 0 in placebo) in the ocrelizumab progressive trial, do it in just like it did for oral cladribine (three verse 0 in placebo. You say there were more in the original publication but some turned out not to be cancer). I suspect one pharma may be lobbying hard for the bad view to be upheld. Maybe the additional RRMS studies will change the view of the regulators, but if the regulators are of the blinkered-phenotype which seems par for the course for reviewers then there will be problems, I suspect.
I hope not
However, the other issue of a successful progressive MS drug, may mean that trials, like the MS-SMART may not be so smart, because if there is a positive result, pharma will surely insist that any drug that is positive in academic studies undergo the same rigour of the process that pharma are made to do.
The academic trials will not have that level of support and it would be terrible if the studies stalled at the end of phase III.
Will it now be worth pursuing the simvastatin story which will take many years to complete, because doctors will be encouraged to prescribe the licensed option?
However, we may get some insight into MS-SMART as results of using prozac in progressive MS are being presented at ECTRIMS 2016.
Anyway, one further nail in the EAE coffin as one more aspect of MS appears to get a solution. But how does it do this ?
CoI None….ProfG may know the answers already and take a different view