@Sector I am glad you have now realised that only 15 patients received treatment in your trial rather than quoting me the original trial protocol . I see that you have acknowledged this in a later post. @Barman76 Thank you for your kind words @BartBart Sorry I could not reply earlier but you worked it out in the end.
Just so I can fill in the gaps on dosing…Mesoblast did indeed use 2m per kg of body weight per dose (in line with the dosing regimen for study GVHD001….(with four infusions over an hour / not injections ) . As the patients in the study I referred too were all paediatric with a mean age of 10 …I would suggest average body weight for a emaciated child this age would be approx 30kgs….so your sums need to be adjusted. Those patients who received a partial or complete response to the first dose would therefore have received around 2 times 30 times 4 =240m cells whereas those requiring a second dose were given a lower dose of 1m per kg…which added a further 120m. No patient in this study received more than 8 infusions or a total 360m cells, based on the mean average weight implied.
I take on board your point about number of cells given per treatment but simply point out that this will only have a marginal effect on our relative project economics as CYP has to pay a large royalty for your licensed IP .
Silviu has already stated he has good reason to believe the cost of goods sold will go below 10% per treatment with volume production of the cells Your point regarding dosing might be of concern if there were safety issues around agglomeration when the dose was infused but that has not occurred to my knowledge in this or any other paediatric study. According to the FDA slides for the ODAC meeting there have been only 3 infusion reactions in total over three Mesoblast study programmes, two of which were easily resolvable but I believe one patient had a reaction to DMSO neurotoxicity (a substance used in cryopreservation which can now probably be replaced by Pentaisomaltose ) and was taken off the trial . Source FDA review slides GVHD001/Protocol 265 and 280. You’re probably not cognisant of the new blood filter upgrades mind you.
Lastly, you ignore the two most important points of my post , which is that Mesoblast were treating patients that would appear to be often on their 4th or 5th line of therapy after steroids and were the most severe grade non responders. To put it crudely, after transplant a Grade B GVHD patient had a 80% chance of survival over 2 years compared to less than 10% for a Grade D/IV. I suggest you spend some time studying Cahn J et al , Blood 2005, for the meta data analyses regarding survival probabilities of different Grades of GVHD. You are comparing diamonds with pearls. I would have used a different analogy but these are beautiful young lives who have perished. Now you mention it, very few companies have ever achieved consistently good results in paediatrics other than Mesoblast. Ruxolitinib has frightening toxicities and about half ? the efficacy in severe grade paediatric patients .The latter point does surprise me because as Rashidi et al and others have shown, older age is a negative prognostic indicator and often requires a 1.04 adjustment per decade…but I believe this does depend on the mechanism of action There you are….I even gave you a real point to go on ! Don’t say I am not fair and factual.
Whilst the recent study I have referred to showed exceptional efficacy , I should also point out that the wonderful J Kurtzberg’s EAP programme also enrolled many patients who had exhausted other treatment options. If our cells our administered earlier as first line therapy after steroids we may in theory achieve even better results.
Lastly, @ddwn Regarding chances of an EAP for Covid ARDS…They are good, but they are not the immediate priority… since I am sure the FDA will want to ensure they have the right in vitro potency assay before allowing either treatment out of the blocks. Post a successful outcome from the ODAC committee I am hoping for a dual BLA application for Remestemcel …but I would not get ahead of ourselves just yet ! So much technical progress appears to have been made from peer reviewed studies of our clinical trials. I provide a link below for the review of two paediatric patients who were given Remestemcel for MIS-C . Note the changes to the important cardiovascular biomarker BNP as well as the suppression of CRP and D Dimer . It would be wrong to make too much of these two cases alone, as the children may have already started some form of recovery but when you compare these heat map studies to other trials, you see a very encouraging pattern . I am very excited for the future..once we emerge from the paperwork. Have a great weekend !
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