The FDA recommended another trial in order to gather more evidence.
Dr Krause who is from the FDA told SI to commission a long term follow up study of the patients by a 3rd party ( In this case CIBMTR registory) as part of gathering further evidence, with no chance MSB could contaminate, alter , cherry pick, post hoc or influence the data at all, whatsoever in any way. It was provided by the registory as factual data, and it does support both MSB's null hypothesis rate, and potency assays.
Both of you need to look deeper than the downramping headline, that is in the first half of the FDA's sentence, the second half being the part you never talk about as it debunks the theme that MSB have gone rouge. On the contrary they have done exactly what the FDA asked for.
To argue an RCT is needed you must understand why that is the case. Why is not throwing out silly sayings like " because" or even " to gather more evidence "
I think, at least some of the long term holders understand what the issue is. It really came down to two things. 1 - FDA insisted MSB explain all previous results, which they did not do a great job of doing ( although they had more data than they showed ) 2 - The TNFR1 potency assay seamed to have been confounded some how, and MSB were not prepared to demonstrate in Vivo how the potency assay worked, ie show the correlation.
The FDA admitted in their matching of TNFR1 levels to patient outcomes in the GvHD trials, there did not appear to be a link between benefit and potency.
We were not given the full dataset the FDA recieved, and so we don't know how they were measuring benefit. It was not done using mortality since that data was not available, and I believe only went for a few months at most back then. Were MSB measuring circulating cytokines at that stage ? Did FDA look at proliferation numbers not decreasing and say this is the opposite to the in vitro lab tests? That is what it sounded like to me.
In the absence then of a potency assay that was linked to benefit, FDA lost faith that the potency assay was valid at predicting benefit, and so could not be sure in that case each dose would give benefit, or that the benefit that was seen, was the result of a potency assay at all.
Enter a request for more data ( CRL ) , which asked for a potency assay linked to benefit, and more evidence that would provide proof the potency assay is linked to more benefit. Here is the downrampers dream where the FDA recommended another trial to generate the data. The FDA had no idea that MSB were in possession of other assays, that it had use spanning all the way back to 2008, and were used in the huge EAP 275 program, and in the gvhd001 trial, so nearly 300 treated patients.
MSB then consulted with the FDA, do you think this IL2Ralpha assay is reasonable? Because we have a load of data on it from 300 patients. FDA said that looks reasonable.
MSB then set about ensuring all their product on the shelf meets the IL2Ralpha potency assay, and were able to immediately demonstrate a direct link of patients that used this assay , and survival rates. They simply took patients that recieved the treatment with the highest potency scores, down to the mid potency grade, and compared survival to the group who recieved the lowest potency up to the middle potency grade.
This evidence that potency is linked to survival was shown in the overall group ( no sub group analysis ) , aswell as grade D, Minnesota High risk and high MAP score, which represents 3 subgroups that are all at the highest risk of death.
The result was scientifically valid in all sub groups, and in the overall study population, and supported the MOA.
The higher the potency score was, the higher the survival was plain and simple. 85% vs near 60% survival overall, but in the most serious groups that had the highest inflammation, survival was over 90% in the high potency treatments, and between approximately 17% to 60% in the low potency groups. Thus demonstrating IL2Raplha potency is a valid measurement of clinical benefit ( survival ) and providing evidence that the cells detect and reduce inflammation, since the most inflamed patients had the highest benefit of all. - supporting the MOA.
Now... what was the point of an RCT again ?
To provide evidence the ( a ) potency assay works, and is linked to survival.
MSB had some of this data all along ( Not the long term survival, and not the other trial results as they were still being conducted at the time )
They have been able to pull together a valid potency assay that is linked to survival and tested, and evidenced as consistent through the Gvhd001 trial, and EAP275 programs.
They have avoided needing to run another 3 to 5 year trial that ultimately if it did ever finish, would have simply shown the same thing, and that's a big If it ever finished.
Ball is now in the FDA's court. MSB has answered all the questions, the potency assay is scientifically significant with the survival linked to potency, the Factory Inspection found no violations, evidence has been provided.
Dr Krause knows what has been submitted, and purchased shares on market.
They should be in labelling discussions right now !
Short % increasing... the more the better, they will only add more buying pressure post approval.
Unless someone can provide a valid counter argument to the above that is more than half of what FDA said, and actually go into depth... I think they've got this one ! $2 party more likely than not!
17 Trading days left !!!!!!!!
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