Ann: COVID ARDS Trial Topline 60-Day Results, page-539

There are a couple assumptions about 'Clinical Trials' being made here by people that are largely irrelevant.

1. These are not normal times, there is a world wide pandemic that ultimately could mutate enough to wipe out entire societies.

2. This was not a normal trial. In conjunction with the FFA, the multiple end points were selected in the face of no vaccine, no treatment that would stop death, no idea why people were dying, no idea on the virus mechanism of action, and no way to check quickly if someone had it. A desire to find anything that would help in any way, mortality, hospitalisation length, ventilation need...

3.if the mortality reduction was 100% in the sub group, adjusting for multiplicity would still not achieve the primary end point. But shows an obvious benefit that cannot be ignored.

4.This is speculation here, but for the sub group that benefited, the company has their profiles of circulating cytokines before, during and after treatment that it would have used to compare with the over 65's. I speculate that the effect of the cells was still there but to a lesser extent over time-meaning further treatment ( repeat or larger doses ) may well have made a difference.

5. Further- the same profiles might allow early identification of the 25% group under 65 that died , where they might also have needed more or multiple treatments for longer because of their own underlying conditions.

It will be telling if Novartis walk. There is no way it will be as simple a decision as some on here have indicated. It won't be a case of them buying into a topline result, the failure to reach an end point, or the P value of a mortality reduction, or an article in a publication. Now in the 5th month of the cooling off period...they are waiting and will be looking to see if the science works entirely. They could have walked months ago if they simply read the headline topline data - clearly they are more interested in what is under the hood, the biomarkers linked with the people that were saved... and in this regard we are thankful mesoblast recorded a gazillion exploratory end points for that exact reason.

As the CEO illuded to, the FDA wanted another trial using Remestemcel-L to confirm it has an effect using biomarker evidence... now they have another one.


Exciting times to be a holder, this month will be more important than the phase 3 results missing the primary end points by far.