I know science isn't black and white. I'm talking about the application of the science in the form of RCTs, which are considered the "gold standard" and my view is they're more of an art. PEs are selected and they're not always what stakeholders want. Results are affected by bias, decisions as to who to include or exclude, unforeseen circumstances, emotion, corruption and fraud. Just because a RCT meets its PE doesn't mean the product is safe and effective.
Take Vericiguat for HF which met its PE. You can see criticism of the PE in one of the letters, that the results might be somewhat statistically significant but not clinically relevant. There's an obvious problem if this drug has to be applied as SoC.
Take MSB's Dream HF. Top cardiologist Valentin Fuster doesn't appear to see it as a failed trial. He says the finding of CRP as a biomarker of inflammation is very important and that inflammation is a key driver. He makes the obvious point that failure is important when you learn something important. I think MSB's "failed" trials are actually very clever in pinpointing the group most likely to benefit.
Re. GvHD. You both confirmed that neither of you know whether or not Dr. Prockop was asked to participate in a RCT. How then can you so confidently assert that SI ignored what the FDA wanted or was avoiding one because he knew it would fail?
I think it's likely Dr. Prockop is related to Darwin Prockop (his daughter IMO). Darwin Prockop is an esteemed biochemist and researcher in cellular medicine who has published many papers including one on potency assays for anti-inflammatory attributes of EVs.
I immediately thought there was a remarkable quality about Dr. Susan Prockop because of her lack of hubris in giving an interview with so much din going on in the background, the way she firmly dispelled the myth that GvHD was good for patients and in so doing, shone a bright light on the greatly differing standards among centers. Even patients who had BMTs for non malignant conditions were still being told absolute nonsense that GvHD was beneficial to them.
Whytee said that it seems premature to dismiss a treatment (Ruxolitinib) after using it in just three patients. That's not what I suggested. If I recall right, Dr. Prockop was very specific about not participating in a trial (from the context, I suspect trialling Ryoncil vs Rux) and being a KOL, she may have based her decision on knowledge gleaned from other sources in addition to her center's experience. It was a good call - this interview was recorded well before Reach2 results were published.
Whytee's comment also ignores the other side of the equation - Dr. Prockop's experience of using Ryconcil. Again, speaking from memory, she talked about using it in a child fairly late on but he still responded completely and was able to come off all immune suppression. I think coming off immune suppression may not be that common, which is why she mentioned it.
DocMcstuffins:
If MSB had run a RCT, they'd likely have recruited from centers which have participated in the EAP (where adults have also been treated) and are therefore familiar with Ryoncil. I'd like to know how you're so confident that patients suffering grade C and D GI aGvHD would agree to a 50% chance of being assigned to a tablet after receiving proper informed consent from physicians such as Dr. Prockop and Prof Kurtzberg who's seen patients "cured" by the product (off immune suppression.)
@JB1975 You've repeated what whytee says a lot, that Osiris managed to run a RCT. These patients were not steroid-refractory and in the most severe category of GI involvement where consensus is their prognosis is abysmal; not only that but since those days, Ryoncil has been improved and physicians become more familiar with the product through the EAP (Perhaps they've also worked out how best to use it ie. by delivering according to biomarkers or only waiting a couple of days after steroid failure.)
You speak of sophistry but what kind of argument ignores the parameters of time and choice? You also don't appear to have learned about the condition of acute GvHD because if you had, you'd know there's no "chance" in the category MSB targets. Dr. Prockop made it clear there are NO spontaneous remissions.
The best reflection Ryoncil works really well is that physicians don't want to subject children to SoC in a randomized, controlled study. For those who claim RCTs are the only way to go, it makes no sense they state MSB could have run one against SoC when the dosing and duration of other therapies themselves haven't been established in RCTs. A trial against Ruxolitinib could never have been done in children because it isn't approved for under 12s.
Regardless of the results of a study in adults, I don't see how it's in any way scientific to make approval for children contingent on adult results for any product, let alone one that responds to signals of peak inflammation.
The apparent recommendation for further data in adults is important because it sounds plausible but makes no sense if you look into it. The intention IMO was always to delay Ryoncil. I think the "FDA" is also lying about the potency assay issue. I really don't buy such pantomime level incompetence or that Caplan would have allowed it to go on so long.
My view is the powers that be want to use Ryoncil to validate the algorithm. I also think the IL2 potency assay is important for other paediatric cytokine storms which are not actually rare, and I'm also finding a lot of papers now mentioning IL2 re. Crohn's Disease. The paediatric IBD market is huge, which could be lucrative for MSB if it makes it.
This is highly speculative but IMO the parallels and contrast are so blatant between MSB's science (which can be questioned) and the other science that can't be questioned (hence the extreme censorship) and I wonder if at some time in the future they meet head on.
MSB Price at posting:
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