Agreed, that @stanjupiter has done an excellent job in his 2 posts above today. On the first one, I thought the issue about RCT is moot given that the FDA has acknowledged that single arm trials can be relied upon in its recently released draft industry guidance on GVHD.
On the potency assay, the subject of his second post, there is FDA guidance (non-binding recommendations in regulatory parlance - refer to the header on each page and the last section on p.15) available online written specifically for the use of potency assays in cellular and gene therapy products. (Search for FDA on use of potency assays.)
I am not aware of any more up -to-date version than this, which was published in 2011. However, some things would not have changed, including on pp.3 & 4, how all potency assays need to abide by a list of applicable biologic and more importantly given where MSB is at, good manufacturing practice regulations. All these accurately describe the commercial requirements, under laws and regulations which the FDA itself has to look at in order to discharge its own legal obligations as an approval authority, that the company is currently trying to satisfy (the last 10% of the work quoting SI). As such, I find the guidance very informative. (As a digression, I do not subscribe to conspiracy theories in general because I would rather think of it as a process whereby I need to do my own research to understand how things work in a complex world, where incentives are complex and may clash in the flow and dissemination of information. We as consumers of that information just need to be extremely careful how we can be manipulated. The onus is on us too to think and decide how we react to information that comes our way.)
Then at the bottom of p.5, the FDA acknowledged that practically, clinical data may not be able to be used to quantitatively test for potency because it is not available until after individual product lot release and they may not be coupled to individual lots. However, it then goes on to provide guidance on how to develop potency assays on pp.6-14. As is quite clear from the recent Type A meeting announcement, the remaining hurdle now is to produce or “pad” the data for what was used in the clinical trial. I have been trying to understand this part of the recent Type A meeting announcement as part of the work foreshadowed by the company. Reading this document gives me a sense what the company should be aware of in terms of what the FDA looks at in order to give a tick. It is also good to know that the FDA has headlined a table on pp.4-5 “Challenges to Potency Assay Development” and supported each of these with examples. While the company works on “reverse engineering” some of these further data, it does not appear to be a completely impossible task, and certainly the FDA is not unaware of the challenges. My sense is, both the agency and the company should have a practical understanding of where each other is trying to achieve.
I hope the company will confirm or elaborate further on what it has achieved in advancing the potency assay, which I think @Phaedrus mentioned in a previous reply to @LeftYahoo as having passed the test for prospective product testing. What it is now doing with the clinical trial data and its inventory has significance for what the FDA will say when the further data are submitted in hopefully a couple of months’ time, whether it would be comfortable enough, in my view only, to allow the treatment to be used on children under 12, while moving on to decide whether the adult registration trial can then proceed.
For me, this guidance document on potency assays should really be read alongside the one on GVHD draft guidance. It indicates to me that the work done on potency assays in the last couple of years has not been wasted, and that the FDA is recognising the unmet need in GVHD. Not yet in an actual approval but it is moving in the right direction. There is perhaps a much more productive process going on than maybe apparent to the market between the agency and the company, and I am decidedly not trying to hype things in crafting this post. Instead, I have been trying to come up with my own assessment of how much confidence I should place on the recent announcement, and I think that confidence is increasing. What would be useful would be a frequent flow of information in the next few months to promote an even better understanding of what the company is achieving and the context in which it is happening. I think that will be very helpful.
(20min delay)