Hi Scott,
Yes it is possible that it could have come from the product, but that will be difficult for anyone to know, even those with the current data set.
If the current data set isn't large enough, then you can't say anything. you can't say if it was or was not product related cause there isn't enough data to go off.
Thus yes it could be product, but as I said it 'suggests', as if it had been product issues, that would make it less realistic to say that it can resolved from doing more trials. If it were to be clearer that it is product then doing more trials would seem a waste of a lot of time and money for Mesoblast.
Regards the IC trial, the primary end-point I do feel is difficult to assess what will be satisfactory and not.
To assess the Maximal Walking Distance is a valid end-point as for these patients of moderate disease severity they wouldn't have any tissue damage yet, but would have pain at rest and pain after walking. So given the walking is the greater effort on the body, then checking against the walking ability is what will be most meaningful for these patients, and of course that also translating into a lower chance of disease progression to CLI.
However yes, I would like to have seen more clarity on what % of increase from baseline would be good, or something clear like the Short Physical Performance Battery (SPPB) score as they are correctly using in the Hip-Fracture study.
We can garner additional IC end-points from the company presentation
"Other endpoints include the change in initial claudication distance,
hemodynamic parameters, quality of life score and the rate of revascularization."
I do not know how well we would need to score on these, but I am happy to see that elements of heamodynamics and quality of life etc are included. For example if the walking distance isn't improved a lot, but the pain at rest, which is a constant issue even when laying down and often wakes IC sufferers from their sleep with pain, we score well on that, then patients will still want it and the FDA can recognise such needs for approval.
If inconclusive, then like Mesoblast we should have had a bigger sample to make the data conclusive of either good or bad.
If not off the charts, then like above I think it will be at the discretion of the FDA to weigh the pros and cons, including potential cost on the value of the observable benefits to patients.
