"Bring it on!!!".
If what I think has happened is correct, you are simply reproducing the same mindset that led SI and the team to the decision of rejection by the FDA.
If you are reasonable (which you personally aren't but I'm going to progress anyway) you should agree that the ODAC questions weren't the first time MSB had seen them. The MSB responses weren't shrouded in shock and awe when they were tabled directly prior to the ODAC meeting. It was the first time WE saw them. Big difference!
If they had been tabled previously and not answered or countered sufficiently previously and then reiterated at the ODAC meeting (as such still falling short) then the outcome was always going to be the same. You and SI believe that the responses were sufficient for the reasons MSB supplied - the FDA DISAGREES! Then (rolling BLA) and at the time of the ODAC meeting. I struggle with SI not knowing this or at least sensing it was going to be the case?? SI has acted like he has been wronged......hmmmmm.......maybe he was ill equipped or unwilling to jump through any more hoops?
The questions tabled prior to the ODAC meeting are FUNDAMENTALS relating to the technology. If the FUNDAMENTALS that form the basis for the solution/technology are 'on the nose' or 'shaky' or 'unclear' or 'uncertain' then the FDA is really left with no other choice but knock it back and think 'well, jeez, we did tell you?!'. You, like SI wants to brush past the questions relating to the FUNDAMENTALS. Do I have to remind SI and you that this is new technology? Do you and SI think that a quantum shift was going to get through on a nod and a wink?
Before your biased and 'sizzle' questions are discussed, the following ORIGINAL and FUNDAMENTAL rolling BLA questions will be discussed in any court environment:
Product Characterization Discussion
1. DISCUSSION: Product quality attributes measured for remestemcel-L are intended to
ensure that key qualities of the drug product are maintained consistently from lot to lot.
Please discuss the adequacy of the potency assay established by the Applicant for
remestemcel-L.
2. DISCUSSION: In addition to discussion of potency, please propose and discuss other
possible product quality attributes or characteristics that could be controlled to better assure
consistent quality of remestemcel-L with regard to safety or effectiveness of the product.
Clinical Discussion
1. DISCUSSION: Limitations of the single-arm study design of MSB-GVHD001 include, but
are not necessarily limited to, the following: a) limited ability to ensure that baseline
prognostic factors, both known and unknown, were similar in MSB-GVHD001 and the
Applicant’s control; b) limited ability to ensure that unknown and known potential
confounding factors (e.g., additional salvage therapies for treatment of aGVHD) that could
influence efficacy outcomes were similar in MSB-GVHD001 and the historical control
group; c) potential bias with selection of patients, subjective nature of the assessments to
score aGVHD d) the adequacy of the historical data to support a null hypothesis.
Please discuss the strengths and weaknesses of the design of Study MSB-GVHD001.
2. DISCUSSION: As noted previously, primary endpoint results in Study MSB-GVHD001
were statistically significant; the measured response was durable (median 54 days). However,
the results of Studies 265 and 280, the two randomized trials, did not provide evidence of a
treatment effect for remestemcel-L in aGVHD, even when reanalyzed using the efficacy
endpoint of Day-28 ORR. In fact, a treatment effect has not been identified in any of the
previous clinical trials conducted in various disease entities, including: Type 1 diabetes
mellitus, Crohn’s Disease, myocardial infarction, or severe chronic obstructive pulmonary
disease and the mechanism of action of remestemcel-L in mitigating aGVHD remains
unclear.
a) Please discuss whether the results of Studies 265 and 280 are relevant to the
effectiveness of remestemcel-L for the treatment of pediatric SR-aGVHD. In your
discussion, please consider not only the similarities and differences in the study
populations, but also any other factors (e.g., number of years between studies;
pathophysiology of adult aGVHD / SR-aGVHD vs. pediatric aGVHD / SR-GVHD)
that you deem relevant.
b) FDA may require an additional clinical trial to support the effectiveness of the
remestemcel-L in pediatric SR-aGVHD. If so, what are your recommendations
regarding the design of such a trial? For example, please discuss the population (e.g.,
aGVHD or SR-aGVHD; adult and/or pediatric), treatment assignment (randomized
vs. single-arm), primary and secondary endpoints (e.g., Day-28 ORR, Day 100
survival, Day 180 survival, etc.), and any other aspects of the trial design.
3. VOTE: Do the available data support the efficacy of remestemcel-L in pediatric patients
with steroid-refractory aGVHD?If these questions were tabled by the FDA in the rolling BLA then the onus was and is on MSB to rectify. MSB (and you) make the mistake of answering the questions to the best of the ability rather than solving the issue of the question. a MASSIVE difference.
Stop cherry picking what works for MSB and takes the conversation away from the real issues. It's deceitful IMO.
There were two parties in the rolling BLA: The FDA which are the experts and veterans of any and all things FDA (funny how that works) and there was MSB with their first ever rolling BLA with their very first Phase 3 FDA trial with a solution that has NEVER been given approval before.
If you take your blinkers off and read the questions above and 'imagine' that the FDA outlined these issues at the rolling BLA meetings you will come to the conclusion that MSB decided to solider on regardless. They decided that rather than heed "FDA may require an additional clinical trial to support the effectiveness of theremestemcel-L in pediatric SR-aGVHD. If so, what are your recommendationsregarding the design of such a trial? For example, please discuss the population (e.g.,aGVHD or SR-aGVHD; adult and/or pediatric), treatment assignment (randomizedvs. single-arm), primary and secondary endpoints (e.g., Day-28 ORR, Day 100survival, Day 180 survival, etc.), and any other aspects of the trial design." they moved forward thinking this step was not required or suitable.
MSB wanted to cut this corner! The FDA says: No.
SI has now made statements that MSB wishes to be granted approval whilst they conduct the trial. From the FDA's perspective, they would have to be thinking, 'we told you that in 2019 at the rolling BLA meetings - looks like you are trying to pull the wool over OUR eyes'. Naughty, naughty....very naughty!
I believe that SI thought he had enough to get it over the line but how would he know? He didn't know, he took a risk. And he was wrong. RISKY from the FDA's perspective.
And the product characterization discussion points are (in SI's own comments) largely inconclusive at this point. As well as additional safeguards regarding quality are offered. RISKY from the FDA perspective.
Add it all together and no wonder it got knocked back! The FDA is not worried, IMO.
MAYBE SI will be ultimately right and the process he is now on will bare fruit. He's never done anything like it before (RISKY). I want to know why MSB didn't take action earlier? If the FDA wanted another trial in 2019, why didn't MSB start one back then?
I hope for the best as a shareholder. I just don't buy into all the 'convenient' crap that gets thrown around here.
Do you people really believe that SI and MSB are not capable of making a mistake or error of judgement? What evidence have you that the FDA is in any way corrupt? It seems to me that you and others don't want to take anything on face value but rather join dots to other things far and wide. No one is talking about the ODAC questions!!!!
I think the ODAC questions are important. Argue with that?
Deal with the issues and move forward is the smart play, IMO. Or keep smashing into the FDA wall with a slight chance of breaking through.
Some time long ago the team at MSB decided they will achieve FDA acceptance. Now they are here and the FDA is the enemy? Makes no sense and I don't accept everyone being surprised at what has happened - it doesn't sit well with me at all!
Surprise is telling us they don't know what they are doing!
Anyway, here's hoping the share price rockets from here! Ha ha ha.
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