An interesting read, thanks for sharing.They are obviously a...

An interesting read, thanks for sharing.

They are obviously a qualified consulting business, so their view is something to note and does appear to have substance behind it. That is they have picked out a few references the FDA made about CQAs not , DP / batch consistency and how it didn't correlate with clinical effectiveness. These are probably the type of things that Mesoblast and the FDA have referred to as 'CMC items', which are not critical enough to call out individually, but are required to be addressed prior to approval.

If it were only these items, I think it would have been a relatively easy CRL to address.

But my first thought in reading what they have said about Mesoblast's CRL, is that they've kind of missed the key point made at the ODAC re potency assays (just look at the conclusion slide, I think they only highlighted one of the several points made by the FDA)... so they either didn't realise or purposely left out critical context, such as the fact that this was a single arm trial and that the potency assays / CQA / MOA proposed by Mesoblast relied on data from three separate data-sets, that is from a trial over a decade ago, the extended access program and the actual phase 3 trial conducted by Mesoblast. On top of that, they also used data from the MAGIC database. All of this was required, because it was a single arm trial.

What Mesoblast proposed for its potency aassays/CQA/MOA relied on the fact that the FDA would accept the use of the presented data from those various sources. Had Dark Horse pointed that out, then I think what they say or conclude would have been a bit more accurate/impactful. But instead they appear to have cherry picked references from the ODAC to possibly fit a message they wanted to make, obviously as a consulting firm, they want their prospective clients to think that they could have helped Mesoblast get a better outcome.

But I believe while there were definitely CMC items to address, the critical flaw was the reliance on data other than the phase 3 trial. The rationale behind it was noble, that is to avoid a randomised controlled trial on these very sick children who have a disease with mortality as high as 80%, but as I've said before, the decision to save a few may end up costing many. I hope that is not the case, but that was a risk Mesoblast, and Dr Kurtzberg took and now they are trying to work with the FDA to overcome this issue.

So in short, an interesting read.. but probably not that insightful given they didn't seem to cover the key issue at hand. Well my opinion of it anyway.

Thanks again!