Aidenb,
I would be very disappointed with these results if I were a Regeneron-Sanofi investor. First of all, there are typically three reasons an IDMC might recommend termination of the study: safety concerns, outstanding benefit, and futility. They have terminated their efforts on the “severe” arm for both, 200 mg and 400mg. I read this as a futility reason (did not work)
https://www.prnewswire.com/news-releases/rege...47326.html
The FDA gave Regenon an adaptive trial:
And, not only they got this, but the primary outcome of P2 is percent change of CPR levels at day 14. That is to say: you have an anti-inflammatory drug, let’s measure the inflammation at day 14 to see it works. Nothing wrong with it, but, did the FDA tell CYDY your primary outcome will be reduction of inflammation?? No, we need to produce clinical outcomes.
And no adaptive trial for us, no sir.
By the way, according to Dr. Yang's data in Southern California we did reduce substantially the blood CPR levels on the majority of patients of the reduced group in which he measured CPR.
Speaking of which, what worries me is that, in spite of reducing the inflammation Placebo-200mg-400mg (-21%;-77%;-79%) respectively the 200mg cohort did not produce positive clinical outcomes .
So, basically they found out that the dosage that might work out is 400mg and the group that might work in is only the “critical”. Well, of course, as we know from the Patterson paper that IL-6 levels are much higher in critical than in mild/moderate (trusting the definitions are very similar). According to BP the difference is very significant (p<0.0001).
Again, this is equivalent to analyzing the data from Leronlimab and say: well, let’s concentrate in the Critical (of your Severe-to-Critical P2) for P3 as it did not work out well with the "severe" part.
Also, it is worth remembering that Leronlimab reduced the IL-6 levels in 14 days with a p-value of 0.0371 to normal levels (p-value 0.3431). I would kill to know the numbers of IL-6 reduction for Kevzara.
What is left for Regeneron-Sanofi ??? With the help of BARDA and FDA who will "lead them by the nose" to the "changing" (or, shall I say: adaptive?) goal, they need to probe clinical benefit for “critical” patients at a 400mg dosage. Their scale is a 7 point and they have defined a 2-point improvement as "clinical improvement" in the report for P2.
Not sure if they will just do a two group parallels analysis (those with and without clinical benefit) test or take the means of the results for all the patients (compared to placebo) to demonstrate efficacy. In any case, they are likely to enter the COVID space only for "critical" patients if the trial pans out with lots of help from government and FDA.
CYDY is not getting any, but I am not worried. At the end the Science prevails. Doesn’ it ???
I would be very disappointed with these results if I were a Regeneron-Sanofi investor. First of all, there are typically three reasons an IDMC might recommend termination of the study: safety concerns, outstanding benefit, and futility. They have terminated their efforts on the “severe” arm for both, 200 mg and 400mg. I read this as a futility reason (did not work)
https://www.prnewswire.com/news-releases/rege...47326.html
Quote:Regeneron and Sanofi reviewed the discontinued "severe" group data, which revealed that the negative trends in the Phase 2 trial (n=126) were not reproduced in Phase 3 trial (n=276), and that clinical outcomes were balanced across the Kevzara and placebo treatment arms.
The FDA gave Regenon an adaptive trial:
Quote:Phase 2: The primary objective of the study is to evaluate the clinical efficacy of sarilumab (Kevzara) relative to the control arm in adult patients hospitalized with COVID-19 regardless of severity strata
Phase 3:
The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with COVID-19 (severe and critical).
And, not only they got this, but the primary outcome of P2 is percent change of CPR levels at day 14. That is to say: you have an anti-inflammatory drug, let’s measure the inflammation at day 14 to see it works. Nothing wrong with it, but, did the FDA tell CYDY your primary outcome will be reduction of inflammation?? No, we need to produce clinical outcomes.
And no adaptive trial for us, no sir.
By the way, according to Dr. Yang's data in Southern California we did reduce substantially the blood CPR levels on the majority of patients of the reduced group in which he measured CPR.
Speaking of which, what worries me is that, in spite of reducing the inflammation Placebo-200mg-400mg (-21%;-77%;-79%) respectively the 200mg cohort did not produce positive clinical outcomes .
So, basically they found out that the dosage that might work out is 400mg and the group that might work in is only the “critical”. Well, of course, as we know from the Patterson paper that IL-6 levels are much higher in critical than in mild/moderate (trusting the definitions are very similar). According to BP the difference is very significant (p<0.0001).
Again, this is equivalent to analyzing the data from Leronlimab and say: well, let’s concentrate in the Critical (of your Severe-to-Critical P2) for P3 as it did not work out well with the "severe" part.
Also, it is worth remembering that Leronlimab reduced the IL-6 levels in 14 days with a p-value of 0.0371 to normal levels (p-value 0.3431). I would kill to know the numbers of IL-6 reduction for Kevzara.
What is left for Regeneron-Sanofi ??? With the help of BARDA and FDA who will "lead them by the nose" to the "changing" (or, shall I say: adaptive?) goal, they need to probe clinical benefit for “critical” patients at a 400mg dosage. Their scale is a 7 point and they have defined a 2-point improvement as "clinical improvement" in the report for P2.
Not sure if they will just do a two group parallels analysis (those with and without clinical benefit) test or take the means of the results for all the patients (compared to placebo) to demonstrate efficacy. In any case, they are likely to enter the COVID space only for "critical" patients if the trial pans out with lots of help from government and FDA.
CYDY is not getting any, but I am not worried. At the end the Science prevails. Doesn’ it ???
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