I wouldn't rule out an AA pathway for the class 2 and class...

I wouldn't rule out an AA pathway for the class 2 and class 3 patients just yet. We know that Silviu recently noted another trial is needed for the class 2 & 3 population and there has been several references that improvement in LVEF at 12 months may be an acceptable surrogate endpoint. I believe FDA agreement on this is critical for AA. If the FDA are agreeable, then the next trial can include both a 12 month LVEF surrogate endpoint and clinical MACE and mortality endpoints at say 3 years. If the 12 month endpoints read out positive, then Mesoblast may be able to apply for AA and the 3 year clinical endpoints act as the confirmatory trial and we can be given full approval once the trial completes. This would allow us to go to market 2 years ahead of schedule under AA. I note this is referred to as a 1 trial approach and has been mentioned as an acceptable approach to AA in the most recent oncology guidelines. Something similar may be adopted here.

So yes, chances of immediate AA for class 2 and 3 based on current trials is very minimal, however, the option above may very well be on the cards. It was interesting that a pathway to approval in class 2 and 3 was not established in the recent meeting as expected, I imagine we may need to wait until formal submission of the trial protocol or it may need to be discussed in the proposed pre BLA meeting for the LVAD population. For all we know this trial may be connected to the LVAD AA as a confirmatory trial etc. A confirmatory trial in the same disease at an early time point is also discussed in the oncology AA guidelines and something similar may apply.

Interesting times ahead.