Convo is not over, just because you found yourself with your pants down once again after a very well-researched post by people you constantly belittle over here, on a stock you own and we don't. Yet you just can't stop preaching "your" facts over here. You don't know and the more you post, the more obvious it is.
Great find @truss20. I actually missed that. The following might have some clues as to why the preference is to not have a direct comparison.
But but but Ryoncil is approved, no other MSC treatment in this indication blablabla.
Ryoncil has been approved, no doubt. But even the sentence that no other MSC treatment will be approved by the FDA due to Orphan Drug exclusivity may be wishful thinking. Ignoring the differences across MSC therapies and manufacturing processes, there are a few things worth noting and in fact, that have been noted along the way.
J Galipeau, to my knowledge not on your MSB HC truthsocial channel, therefore his published articles MUST be taken with a grain of salt (I'll take the liberty to highlight a few things using ****):
"Gut and liver GvHD are more responsive than skin GvHD. In the absence of robust predictive biomarkers, these observations **provide guidance in clinical trial design biased toward subject selection likely to be responders**. These data likely informed an adaptive clinical trial design for NCT02336230, where identical MSC products and dosing schemes in both studies were maintained but the definition of response, age of inclusion, severity of disease, and exclusion of skin-only GvHD as well as a more aggressive start time for MSC transfusion were implemented (Table 2).
[...]
In the absence of robust predictive biomarkers of response, the judicious use of clinical observation and subgroup analysis of responders and non-responders in early-phase clinical trials **may inform the rational selection of patients enrolled in advanced clinical trials to bias toward outcomes meeting primary clinical endpoints of success**."
https://www.sciencedirect.com/science/article/pii/S1934590918302224
Could this be?
"Absence of data to support a null hypothesis, considerable concerns related to bias due to the single-arm nature with differences between the study group and the external control group in baseline prognostic factors, concomitant medications, absence of a clear MOA and the observation of ORR predominantly **in a trial that enrolled a substantially higher population of lower GI involvement where assessments may be subjective**, the absence of data to support Day 28 ORR as an the optimal endpoint are factors that contribute to this recommendation."
That's the comment from the reviewer leading up to CRL#1, which can be found here:
https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/ryoncil
"* Prochymal significantly improved response rates in patients withsteroid-refractory gastrointestinal GvHD (88% vs. 64%, p=0.018, n=71).
* In pediatric patients, Prochymal showed a strong trend of improvement
response rates (86% vs. 57%, p=0.094, n=28)."
https://www.fiercebiotech.com/biotech/osiris-therapeutics-announces-preliminary-results-for-prochymal-phase-iii-gvhd-trialsProchymal - children and GI. What patient group was substantially higher represented in your P3 single-arm trial?
I'll leave the organ involvement at baseline at that for now.
There was however something else that I considered to be interesting, the underlying stem cell transplant that lead to GvHD. I'm sure you have noticed that as well, right?
What was the ratio in your single-arm P3 trial?
Bone-marrow 30/55, so majority of the children treated received initially a bone marrow transplant that caused aGvHD to develop.
Is that a real-life screenshot? Are most stem cell transplant bone marrow ones?
What about the real-life Temcell evidence in Japan, published by Murata - what was the ratio?
90/309, less than 1/3. Interesting.
https://pubmed.ncbi.nlm.nih.gov/33976381/What was the ratio in your previous trials, the one that didn't meet its primary endpoints?
20/163 in the remestemcel-L + SOC group and 14/81 in the placebo + SOC group, 12% and 17% respectively.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7060124/Makes you wonder, why your single-arm P3 trial seems to have such an unnatural selection of patients that have initially undergone peripheral blood stem cell transplant.
Maybe - but without "firm conclusions", lets see what the FDA reviewer noted:
https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/ryoncil
Based on the above, I'd even argue that there may even be room for a clinically superior MSC product in that ill-represented sub-group of patients that received a PBSC stem cell transplant and if the untampered ratio is right, that may even be the largest sub-group of patients with SR-aGvHD.
Your response, something very smart, and Cynata, and cool vibes, and Ireland, and [who gives a crap]. You want to preach and teach us, please do. But we can all see that you can't handle replies.
But Ryoncil has been approved, yes, again, in December 2024. Could it have been approved earlier? There are a few comments amongst the FDA records that the ambulance chasers in their court cases would have loved to include if knlwn at the time, for example if you change your manufacturing, you have to let the FDA know and they may request a comparability study.
Did you know that MSB submitted a comparability study back on 9th October 2015 to show the manufacturing changes and the FDA did not agree with it?
https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/ryoncil
8 out of 54 patients in your single-arm P3 trial received MSCs from DP2, while 46 received MSCs from DP3.
https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/ryoncil
Bauer mentioned it even during ODAC, however, at the time we didn't know exactly what he was talking about, although I had my suspicion when discussing it with JB1975 here:
https://hotcopper.com.au/threads/2021-year-of-the-boom.6097217/page-6#post-59877446
Bauer said:
https://www.fda.gov/media/143337/download
@JB1975 in case you are still reading this, now knowing the date when this study was submitted by MSB to the FDA, that between 2015 and 2019 when MSB started the approval filing, they would have not received any feedback from the FDA regarding the comparability study not being accepted?
And with this study not being accepted, why use that same product in their COVID trial?
Anyways, Ryoncil has been approved, Ireland, cool vibes, and the same people are still involved in your trial designs going forward.
We can also discuss the FDA's wording "may" when it comes to approval chances of a single arm P3 trial, as communicated, but I can see that the word "may" is likely another word like "just" that will fly well over your head since it doesn't suit your agenda.
The above released data will hopefully give us Cynata holders enough points to see how the data in our P2 trial stacks up - or if the first line treatment should be put on ice, right next to Japan.
Michelle over and out.
(20min delay)