Najima et al. (who are KOLs, very familiar with aGvHD and pioneers in FMT for SR cases, which Malard et al. (Nature, 2023) say looks to be "one of the most promising approaches") do not appear to agree with you that the trial NCT00366145 failed.
We know now the cells respond to the most severe inflammation (independently confirmed by Dr.Lightner) and NCT00366145 included milder cases of skin, which caused it not to meet its overall PE; however, Najima et al. say, "Prochymal significantly improved the response of liver（76% vs. 47%, P＜0.05）and gut（82% vs. 68%, P＜0.05); the response of skin was not significantly different between Prochymal and the placebo groups（78% vs. 77%, P＝0.9)"
The trial was poorly designed. Steroids are well known to do an effective (quick but often temporary) job in skin but don't work that well for gut, which is a problem if OR is the endpoint. I've been through in detail most of the therapies listed by Malard et al. for SR aGvHD and while many give good OR, even CRs, they don't correlate with survival. Only 1/3 of responders to steroids get a durable response. That's well known.
Another concern I have with response at 28 days, particularly for skin, is that it may not be long enough to see results for a product that responds to the inflammatory milieu of the individual, a therapy that supports the natural healing process. The body likes to heal in a certain order (I found this by observing the process of Red Skin Syndrome in my daughter) and the cells could be engaged in healing the connective tissue first and it could be that a longer period of observation is required for visible results in skin.
That said, MSB had the confidence to include severe cases of skin only in GvHD001 which got impressive results through a combination of improved technology and better selection of patients.
You've complained before about the dearth of raw data. I agree with you to an extent but what I have seen points to something phenomenal (ie. the subset of severe lower GI matched with patients in the MAGIC database according to biomarkers where OR correlated with survival and being able to come off immune suppression; In HF, 2 patients in the LVAD MPC group had their devices removed and hadn't undergone transplant after a year vs no controls, which is consistent with what Dr. Perin said about an early trial. Out of 17 patients, 2 who could hardly move were out jogging on the beach after treatment)
It's the
degree of improvement from baseline in quite small cohorts. Identifying the right patient and the timing could be key to reproducing that difference in greater numbers.
This is not a scientific thing to say but I know awe when I see it. I'll never forget the interview with Dr. Keren Osman of Mt. Sinai about the EAP results in CARDS. I think Reme was delivered here appropriately, according to biomarkers.
When my attention is being drawn to something I always wonder what I'm being distracted from. I don't buy the issue with the potency assay at all. I think there was a problem with consistency in the past but technology (AI) has likely solved that. The key IMO is the individual, the wanting to validate an algorithm because it's more scientific than RCTs, which can give misleading results because of poor design and other factors.
https://www.researchgate.net/publication/318482034_Mesenchymal_Stem_Cells_The_First_Approved_Stem_Cell_Drug_in_Japan
(20min delay)
