I wrote some months ago, that if we failed this FDA hurdle, then I believed that we had all been lied to.
That a class action would probably ensue.
And... Here we are.
I, like many here, believed what we were told, and that was that Si and the team were hand- holding the FDA, on the path to approval. That all their objections would be telegraphed to us and we WOULD overcome and prevail.
And yet.... here we ARE.
i'M HUNDREDS OF THOUSANDS OF DOLLARS DOWN.
And we are now faced with the flip of a coin!
Will we even get the A meeting?
What's the new evidence that we can present? The Covid trial?
will they even look at that, success or not.
This was the simple first step. Everything else would follow.
I believed all of our ducks were lined up. That's what we were told.
They obviously weren't.
For all my long term friends on here, please read this with an open mind
Copied and pasted from ? but greatly appreciated
You guys remind me of diehard football supporters back in clubrooms after their team has just suffered a disastrous loss. After a few beers everyone agrees the cause of the loss was bad umpiring.
My opinion is that your team (MSB) lost because they missed two set shots 20 meters in front of the goal posts.Imagine clinical trial has million moving parts most of which are not under the direct control of the sponsor.
But the one thing that was completely 100% in MSBs control was creating the control group 28 day ORR estimate in the pivotal P3 single arm trial.Everything hinged on this because it would be the difference between the ORR rate achieved in the treatment group versus this hypothetical rate that determined efficacy.Common-sense tells you that the rigour through which you derive the hypothetical control estimate should be commensurate with the rigour by which you derive your treatment arm rate.
So what MSB actually?
Well probably no more than a couple of hours work. MSB started with what thought would be anticipated ORR for children receiving the treatment – 65%. Then it posited what would be a clinically significant effect – 20%. Therefore, 65%-20% = 45%. for the control estimate.They then conducted a cursory checking of 4 papers in the literature and found the 45% estimate was in the range of patients receiving SOC. And so the trial was good to go.You will not find anywhere in clinical trial history anyone that constructs a control group estimate like this.
It completely lacks any rigour. Anyone (as the FDA did) can find other papers that have a different (higher) estimates.MSB needed to work forwards not backwards.
First establish the likely outcome for children not receiving the treatment from a proper systematic and reproducible review of the literature. Lets this say produced a 45% figure. Next posit your estimate of what would represent a clinically significant improvement (say 20%). Then calculate your sample size to this difference of 45% to 65%.But why is working forwards better than working backwards if the answer comes out the same? Because by working forwards you are forced to provide a proper justification for the 45% estimate at the start. It doesn’t drop out thin air as it did for MSB.
Naturally the manner in which MSB had calculated the control estimate was rejected by the FDA.
This occurred over a year ago. MSB informed investors of this in a very obscure way. Buried on page 22 of the 231-page of the 2019 AR in a section of template / boiler language:“For example, our Phase 3 study for remestemcel-L, which met the primary clinical endpoint with statistical significance, was conducted as a single-arm study due to the seriousness of the condition, the rapid clinical deterioration of affected patients, the mounting literature suggesting a meaningful treatment effect, and the position in the medical community that a randomized controlled trial was neither feasible nor ethical in this patient population. While we intend to provide the FDA with comparator outcomes from control subjects, it is possible that the FDA may not find the data sufficient for approval.”At the time trying to understand this paragraph was nigh near impossible.
Investors would have assumed that MSB already had a comparator; the 45% estimate. So why was it “intending” to provide the FDA comparator outcomes from control subjects; long after the trial had finished?Because their first effort had been rejected. Having had the first control group estimate rejected you would have thought that now that MSB would pull out all the stops in its next attempt for a set shot in front of the goals.This was the MAGIC study.What did MSB do?
It failed to submit to the FDA a Statistical Analysis Plan for how exactly the MAGIC study was going to produce its estimate. By failing to submit this MSB were condemning whatever estimate was produced to be exploratory in nature. Not confirmatory. So this in time was also rejected by the FDA.MSB had run out of free kicks.But why then did the ADCom members vote 9:1 if the trial was so fatally flawed? I suspect the AdCom members put their clinical detective hats on and answered a different question to what was actually being asked.
From divining the tea leaves their best guess was that there was signs of treatment efficacy.But was this evidence generated from a well-controlled trial?
No.
In fact as one member (who voted yes) commented the trial was really just a series of 53 anecdotes. Nothing any of the AdCom members said would have caused the FDA to rethink their view that the pivotal trial here was not well-controlled.
And so positive evidence from a small poorly controlled single arm trial is never going to trump negative evidence from larger more rigorously controlled trials.
No matter that trialists will tell you absence of evidence is not evidence of absence.The root cause of this. What big pharma learnt decades ago. The very worst people to try and produce confirmatory efficacy signals are the people who developed the product in the first place.To them it is self-evident the product works and it should be out their saving lives.
Trials are viewed as bureaucratic devices; focused on procedural correctness that comes at the expense of helping people. This might be a good headset for convincing shareholders to open their wallets. But not such a good headset for a regulator.
My words now.
So, where are we now?
Honestly?
I don't know.
I do know I've ;lost a lot of FAITH (and money)
The magical bus, driven by Si, taking us to our futures, has suddenly got flat tyres.
Our future suddenly looks like where we've been.
I am bitterly disappointed. And that's not the first time with MSB
This smells like bull shit.
I've currently got sell orders in for different parcels, (my first sells in over ten years)
I want to actually get something for my steadfast support, I'll buy back in under $3
Imagine the opportunity cost I've endured?
Can Kingtup still buy his yacht?
Celestial, Wow I feel for you
All the good guys, My "island" friends, you must be as shattered as I am
Weren't we all told that Si was a long term FDA Advisor?
So WTF?
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