@ukpdam just a quickie , to help. If you read this study I think you will see that TNFR1 is an excellent bio marker but it is not quite as good as ST2 which outperforms any panel combination of anything else .
https://www.sciencedirect.com/science/article/pii/S1083879118309534As you can see from the graphical illustrations TNFR1 gives a good account of itself as a prognostic bio marker . I can’t find the recent study that shows how ST2 is the only bio marker which is uncannily accurate in children under 10 with srGVHD.
Some biomarkers should also get a creditable mention , like Elafin which is particularly good with skin GVHD.
https://www.frontiersin.org/articles/10.3389/fimmu.2021.516078/full Remember an accurate bio marker may inform doctors the likellihood of a severe outcome (non responder) very early in the treatment process when there are few symptoms using standard clinical graded classification scores . This allows stronger dosing or alternatively quicker tapers from steroids for those not likely to progress to a more severe condition.
When you appreciate the accuracy of these MAGIC algorithms which utilise the latest machine learning techniques in interrogating the meta data of patients with GVHD you realise how petty and pathetic the FDA are in questioning the lack of a placebo control in our last Phase 3 . Indeed if you really want to get annoyed , look at results for Kadmons Belumosudil as treatment for Chronic GVHD. Despite managing to cure a significant percentage of patients who were refractory to Ruxolitinib and Ibrutinib the FDA still has approved it only as a treatment AFTER at least two lines of existing approved therapies have failed . I mean seriously, do these clowns at the FDA have a clue ? They seem unable to prevent therapies they have approved being used as the first line options despite lower efficacy levels. Meanwhile they frustrate the entry of much safer , better tolerated and effective alternatives because they fail to adequately stratify treatments for various types of GVHD to allow the most effective for a particular organ such as liver or GI in acute srGVHD. These errors cost the lives of many in the FDA pursuit of rigorous , well controlled and randomised trials … Don’t the FDA get it. The grading system is not as accurate as the ST2/Reg3a bio markers that they criticised Mesoblast for using with the Magic retrospective analysis . If I showed you how the clinical trials system is manipulated by big pharma you would be astonished and disgusted … and it’s all perfectly legal . It’s Silviu’s job to educate these people politely to understand what they are regulating . He must be incandescent inside at all the delays …and deaths!!!
https://investors.kadmon.com/news-releases/news-release-details/kadmon-announces-fda-acceptance-nda-belumosudil-patients-chronicThe points above should not come as a surprise to anyone. In the last few years we have seen the car companies use defeat devices to avoid emissions testing , flash boys to manipulate HIgh Frequency trading etc etc . Big business will always outsmart these guys . When Bauer’s team wanted to show their machine learning studies at the ODAC meeting they used totally misleading data . For example , Mesoblast never uses cells which have exceeded more than 5 passages in total . Bauer insisted on showing the effect of putting cells through 7 passages ! Totally irrelevant information. Most of his research had been worked out by Kaplan over a decade ago.
Please do not rely on the accuracy of any facts or opinions in the above post when making an investment decision. OP
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