Bazsa wrote:
"So at what stage do you think we are at now?"The yellow highlighted statements by Dr Eric Rose that
"the potency assay that we originally proposed had problems" and "
And we've reverted to a new potency assay that speaks to the mechanism of action of the cells as an anti-T cell entity" are having a big impact on my thinking about what stage MSB is at.
This is because Dr Eric Rose is MSB's Chief Medical Officer and the person at MSB that is most responsible for preparing the BLA resubmission and so his statements matter a lot and his statements in my opinion are a departure from the messaging that the company had been sending out. I don't think anyone else at MSB has admitted that the potency assay had problems before Dr Rose did. And I think that those problems are not just communications problems or perception problems due to the FDA (or OTAT) misunderstanding the data they have, but are in fact substantive technical problems requiring a new potency assay. I think that's a hard conclusion to avoid from Dr Rose's own statements. Until Dr Rose made those statements and I'd properly considered them I was able to imagine, because of what I still didn't know, that MSB was a lot closer to being able to make a coherent argument using biomarkers related to survival to rescue the pivotal trial as being an adequate and well controlled trial.
Now with the additional information from Dr Rose, I am reminded of and have been revisiting statements made by the FDA's in their ODAC briefing materials and presentations as recorded in their slides and the transcript which were very powerful sounding (on the science, in my view) criticisms of TNFR1 as a potency assay.
The problem I see for MSB is that, Tumor Necrosis Factor Receptor 1 expression, was absolutely integral to it's ODAC presentation. It was only on the basis of showing stronger TNFR1 expression after some manufacturing changes were made in the production of the product in 2009 that MSBs selecting of data from different clinical trials made any sort of sense to me.
IF MSB has to pivot away from TNFR1 expression to some other new potency assay then I don't see how they can credibly do that. It will look like they are casting about to try and find data to fit what they want to be true even if they are not doing that. I'm not saying that they can't. I'm just saying that I can't currently see how they can credibly shift away from TNFR1 expression as the potency assay. If I knew what exactly was the problem with the potency assay, then maybe I'd have a clearer understanding but Dr Rose hasn't shared that information.
The thing that is really important about the potency assay from the standpoint of rescuing the pivotal trial as being an adequate and well controlled trial is that, unlike patient biomarker data which can be looked at after the trial, and patient matching which can be done after the trial, the actual product that went into patients cannot have been subject to any new potency assay (the potency assay was also a product release test) that is adopted now, its too late for that.
Science is largely about correlating things. If there was a problem with the potency assay that was used as only potency assay available at the time that products went into patients then there is a problem with knowing that patients got treated with what effectively was the same product.
A new potency assay instead of TNFR1 expression, perhaps IDO or something else that relates to an ant-T cell mechanism of action, that wasn't used before seems to necessitate a new trial be done. There is no time travel option available to go back with the new assay to product release with it and so put the better assayed product in the pivot trial patients that already got the product.
(
@Phaedrus - I'd written a long and perhaps too rambly response to you that didn't go through when I hit the post button - by that I mean that I had decided to post it - hit the post button and then sat waiting for maybe 10 seconds or so to see if it would go through and when it still hadn't I aborted out of trying to post - I was conflicted because some of my long posts are in my opinion long because they need to be to work logically through things step by step but sometimes they are just long because I'm a bit waffly and should do more proof reading and editing to be clearer.)
(20min delay)