banter and General Discussion, page-4714

https://www.nature.com/articles/s41409-022-01741-3#MOESM1

"The possibility that somepatients might have responded to concomitant therapies rather thanremestemcel-L cannot be excluded".
@JB1975
Whilst your clinging on to use of the word “possibilities” , let me point out the difference between those that were treatment naive and those that received prior biologics as shown by the responder and non responders rates in EAP275 (found in the Supplemental Appendix-see below table S1 from astctjournal ) . Despite the relatively large sample size for a SR aGVHD dataset, there is nothing to suggest any material difference in outcomes between those who received a prior therapy and those that did not. Indeed, in normal circumstances this would be an unusual observation to make.

Bearing in mind that most patients in EAP275 were salvage therapy patients and had often already received three non steroidal therapies by the time Remestemcel was administered i would say the Overall Response Rates considering the Grade C/D percentages was exceptional …and this was achieved using cells from 11 different donors with multiple product lots ! I also show a link above from an excellent article in Nature (see below), showing the results of a another large trial of sr aGVHD patients where the first line therapy for refractory patients was Ruxolitinib, but other Best Available alternatives were administered as second and third line treatments to non responders. Please observe a declining overall response rate (see Figure “a” as subsequent treament options are exhausted ….which is what you would normally expect in salvage or “treatment of the last resort” patients.

The simple fact is that in the last TWENTY odd years, there has been very little progress in the Overall Survival outcomes of Grade C/D sr aGVHD . Have you ever asked yourself why Mesoblast is so keen to provide the FDA with an analysis of their EAP 275. I believe the answer lies in the data showing superior dosing strength achieved post modifications to the therapeutic process for Ryoncil alluded to in the ODAC meeting. I would postulate that improved overall survival and in vitro potency assay data, will establish the clear link that the FDA has been requiring . I would point to similar efficacy results in both the EAP and GVHD001 Phase 3 trial , to show consistency in the data. As Silviu mentioned to the ODAC Committee the small dataset from just the GVHD001 alone was never going to be enough to show statistical significance …but I would postulate that including the 241 patients from the EAP will make it pretty bleeding obvious ! The FDA has a dispute process to work through but, in my opinion , anyone with a modicum of understanding about Grade D sr aGVHD non responder rates especially those patients with validated biomarker MAP scores over 0.29, will know that Mesoblast is head and shoulders above any other approved therapy.



https://www.astctjournal.org/article/S1083-8791(20)30059-8/fulltext

Therapy response to sr aGVHD

Table S1. Summary of Overall Response at Day 28 by Baseline Characteristics

Baseline Characteristics

Responder' Non-responder p-value