@captainpaul. There is a fair deal of cynicism in your comments...

@captainpaul. There is a fair deal of cynicism in your comments . Frankly I am not surprised . When I look at this industry I see one company after another doing exactly what you are suggesting ... changing endpoints part way through trials and data mining p values to find some clinical significance to their work.... but I think you are wrong about Mesoblast on several counts. I would prefer you hear the reasons direct from the management because you will have the ability to cross examine the answers at feel more comfortable holding the stock .
The FDA is interested in the total disease burden and total pharmacoeconomic costs of therapies . Put simply time to first event analysis is not able to quantity healthcare costs per patient properly . A joint frailty model focussing on actual MACE events is a much more relevant and modern method of determining results . Using an enriched patient group allows the number of events required to power a trial without having to increase enrolled numbers to thousands of patients at significant time and cost. So Mesoblast did not have to “justify its approach“ by issuing a paper.. it has been widely praised for adapting a trial to more relevant endpoints after discussion with the FDA. In fact I hear that it is being looked at as a template for many clinical trials going forward. For what it is worth , I believe the phase 3 trial will meet the original endpoints but it is just the statistical powering ( in terms of number of events) which may have made it more difficult to achieve the required p values with a smaller number of outcomes... but you know this.
I also think your assessment about the relative effectiveness of MSC treatment in grade 3 heart patients vs grade 2 is incorrect. It is my understanding that the polarisation of M1 to M2 macrophages shows the best results in the sicker patients... reflected by the SR GVHD results in Grade 3&4 patient groupings. Lastly you should be aware that the LVAD trial was independent of Mesoblast. The primary endpoint was not chosen by the Company and the large number of Bridge to Transplant patients and thrombotic devices skewed the results badly. Interestingly I have heard that there were a number of patients successfully weaned of devices after the trial had finished . Furthermore in the non ischemic sub group there were a number of “genetic” heart related complications in the younger patients which were always likely to make our treatments less effective. The devil is always in the detail as they say.
When someone as knowledgeable as you is posting , people might consider what you say to always be accurate... so please talk to the management before jumping to conclusions. If you still disagree having heard their explanations I will be interested to hear why . Please keep up the posts because you can help all of us with your expertise. I will take a break from posting for a few days whilst I am travelling. Happy New Year everyone.