Ann: DMC Completes Final Review of Phase 3 Heart Failure Trial, page-71

Stanjupiter, what a wonderful and thoughtful post. Please remember that the centrepiece of the Circulation Research article was around our ability to affect levels of eNOS which is an important protective molecule in the vasculature and responsible for most of the vascular NO produced. The Prof has also mentioned how important the process of macrophage polarisation is..so do not underestimate that part of the therapeutic effect.


Let me follow on by saying that I have now checked and i have been advised that, if, there was a stopping rule for overwhelming efficacy it had be lodged with the protocols on the clinical trials register. There is none. Mesoblast has confirmed that this is the case. The reasoning behind this is (as I correctly stated before ) is that whilst the trial would be stopped for safety and efficacy the FDA needed to have at least 5 years clinical data .
Frankly I am not surprised. The recent failure of Incyte’s second generation drug itacitinib in severe grades of adult GHVD leaves the door wide open for Mesoblast. What most people forget is that the FDA approved ruxolitinib (Jakafi Incyte Corporation ) for SRgvhd in adult and paediatric patients aged 12 years and older was based on an open label, single arm, multicenter study of only 49 patients including Grade 2 patients. Interestingly this was based on the Mount Sinai Acute GVHD International Consortium Criteria... this was the same MAGIC consortium which has just completed a control data study of 30 matched patients from their contemporaneous database using best avaliable therapy against the efficacy of Mesoblast’s phase 3 results. The result of the later study is that Mesoblast has provided overwhelming evidence of its clinical superiority and I believe it would be unethical, post its approval , for it not to be used “off label” in adult srGVHD . I am also pleased because of the toxicity profile for Jakafi whose debilitating side effects were tolerated because it was the only real therapy available.
Secondly, as regards the LVAD trial, I have spent a great deal of time looking at the data. This trial was very poorly structured allowing different hospitals to continue using their own preferred LVADs rather than having one particular make. There is of course big differences between pump thrombosis rates between different devices. The “problem” LVAD was originally given to 40% of the enrolled patients . It is my understanding that many of the patients were simply too frightened towards the end of the trial to allow the devices to be turned off to allow a weaning test . These patients were marked down as a fail . If the patients had been given the latest Abbot LVAD I am pretty confident Mesoblast would have achieved its primary endpoint.
Furthermore, I have been assured that virtually all the bleeding events in the LVAD trial related to the large ischemic subset. I take the point that others have made about the average rate of hospitalisations being the same as the control group...but this is a complete red herring because of the trial complications. The ability to substantially reduce bleeding events in ischemic patients was a major success. Remember also that when you are hooked up to a continuous flow device you cannot expect many of the benefits of an improved level of ejection fraction resulting from a remodelling of the left ventricle which was so apparent in the phase 2 results. I therefore believe that the results of the LVAD trial are not going to prevent a successful outcome for the Dream CHF trial. On the contrary. I will explain in my next post why I think the share price of Mesoblast should have risen substantially over the last month based on information provided to the market.... but first I have to go to an engagement. I am very excited right now .

Please do not rely on the accuracy of opinions expressed in these posts when making an investment decision. I could be the cleaner . OP