Still feeling the frustration from the CRL, Gonna take some time to get over that, not gonna lie.
As a result, been doing a lot more reading, as one would being an investor in MSB. I've been seeing a lot of reference to 'manufacturing' issues, 'potency assays' and the like. This was I'd say due in most part to part of the announcement MSB released, shown here:
"The FDA also identified a need for further scientific rationale to demonstrate the relationship of
potency measurements to the product’s biologic activity. Assays measuring the potency of
remestemcel-L will continue to be refined to provide further scientific rationale for its use in severe
inflammatory diseases with high mortality risk, such as SR-aGVHD and COVID-19 ARDS."The FDA are just not happy with MSBs quality markers and/or the manufacturing process. I don't know enough to comment why. MSB say they have it under control. FDA says they're not convinced. So this is a fairly serious problem. If the FDA don't trust the process, what chance does any stem cell therapy from MSB have.
So digging a little deeper, I came across a section of the ODAC briefing documents the FDA released that covers where the FDA stand in terms of potency markers and MOA, shown here:
"The second approach is to use clinical performance to demonstrate potency. For instance, if a product meets the primary clinical outcomes, has been extensively characterized during product development, and is produced by a well-controlled manufacturing process, these clinical data may be considered to demonstrate potency even if the mechanism of action is not completely understood. In this scenario, assays purporting to measure product attributes thought to be related to product potency must be sufficiently robust in terms of reproducibility and as indicators of product quality and stability. This approach can allow novel therapies with clearly demonstrated efficacy and well-controlled manufacturing processes to progress to licensure even if the mechanism of action and its relationship to the relevant potency assay are not completely understood."
https://www.fda.gov/media/140988/download (page 6)This to me says, even if you don't fully grasp what is going on with the therapy, as long as you can show it works, then we'll accept it. This to me is a big driver behind the FDA wanting to see another randomised aGVHD trial. I personally think aGVHD is dead in the water for the next few years (recruitment time, costs, potential market size, just don't see it being worth it). I don't see the FDA granting conditional approval either. Decision is made, we need to move on. ARDS is the next hope and here I take a positive view for MSB the the 'second approach' as the FDA call it is a pathway to approval still even if the FDA don't have faith in the quality markers MSB use for their batching and quality controls (since the ARDS trial is the 'gold standard' to prove efficacy).
We need a clear and decisive result from the ARDS trial. Put all doubt and uncertainty to rest. Doesn't even need to be 'overwhelming' just a clear clinical benefit. A clearly successful result for a world stopping pandemic would be a huge win for MSB. Fingers crossed!
(20min delay)