You may not believe that GVHD001 had a positive outcome, but even the FDA reviewer, Kristin Baird, is quoted as saying it did (see link abstract) you mixed up the primary with the secondary endpoint before going on to make your calculation …you then failed to use binomial distribution for calculating the p value which was determined prior to the commencement of the trial. ..you said that none of the trials for GVHD were published in a journal..that is not the case as EAP275 and GVHD001 were both published in ASTCT. You suggest the positive results could have happened by chance or been the result of cherry picking…maybe 10,000 to 1 ?…i will grant you…but Prof John Levene (the worlds leading expert? on sr aGVHD and founder of the MBS algorithm) pointed out in the actual ODAC meeting, that the severity of disease at baseline plus the MAP biomarker scores show that the opposite is likely to be true ..see P values above . The argument used by Baird and her team to discredit the null hypothesis used in the trail GVHD001..was littered with material inaccuracies such as misrepresenting the efficacy of alternative treatments which had much lower response rates..in one case she quoted from the efficacy rates after an additional third and fourth line treatment had been administered ,rather than the lower number of the second line treatment which inflated her response rates.
Baird was left looking pretty stupid when it was pointed during the ODAC meeting that Ruxolitinib had achieved a lower response in severe grades during one of the Reach trials , than the null deemed too low by the FDA to be used by Mesoblast (45%) …one of the FDA review team was left suggesting that Ruxolitinib was a previously approved therapy for other indications, so this was not as important. I could go on , but what’s the point ? The FDA wants more data to conform the accuracy of the potency assay …In my opinion the Magic Biomarker Score above 0.29 to show high risk grade is now a validated and commonly used method for stratifying risk for steroid refractory aGVHD. I believe it to be a far more accurate method for patient grading than that used for RCT clinical trials …and has been tested over thousands of patients . The FDA is talking out of its ar$e but Silviu has to shut up and do as he is told…because they are the referee .
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