The clinical results of Kevzara (Sarilumab) trial
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Posted On: 06/19/2020 6:29:26 PM
The clinical results of Kevzara (Sarilumab) trial can teach us some lessons. The FDA is taking them “by the hand” and gave Regeneron an “adaptive” trial, AKA “let’s throw the spaghettis to the wall and see what sticks”:
Not only they got an adaptive trial but in P2 the primary end point was the lowering by inflammation as measured by C-reactive protein (CRP). As we know, Kevzara is an anti-inflammatory drug (interleukin-6 (IL-6) receptor antibody) used for moderately to severely active rheumatoid arthritis. Basically, they told Regeneron: please show us that you can reduce inflammation. Is like asking CYDY, please show us that you can show occupancy of CCR5.
In any case, the results for mild to moderate where disappointing (maybe because the levels of IL-6 are lower for this condition), as where the results for 200mg in the “critical” group.
Only results for 400mg in the “critical” cohort stuck to the wall.
So, what can we learn? Well, the 200mg group showed a very similar response as far as % of change in baseline CRP: -77% (200mg) vs -%79 (-400mg) and, yet, the death rate was higher than for placebo: 36% vs 27%.
That is, measurements of the primary end point did not translate into clinical outcomes.
Frankly, I would be worried about the results of P3 with 400mg as the correlation does not seem well stablished. The clinical improvement for 200 mg was 51% vs 59% for the 400 mg arm (41% placebo). So, apart from the reduction of IL-6 in measurements carried out by Dr. Patterson and the reduction of CRP in those made by Dr. Yang in our patients at Montefiore we will need to show clinical results (as our IND patients have been demonstrating).
Another lesson for us is that they (FDA + REGENERON-SANOFI) defined “Clinical improvement” as a 2 point improvement on a 7-point scale (1) death; 2) hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4) hospitalized, requiring supplemental oxygen; 5) hospitalized, not requiring supplemental oxygen – requiring ongoing medical care (COVID-19 related or otherwise); 6) hospitalized, not requiring supplemental oxygen – no longer requires ongoing medical care; 7) discharged from hospital.).
This translates to 1.14 improvement in a 4-point scale.
The good news is that for us, such a difference for the means of our trial should likely yield a very small p (if FDA keeps consistency). So, an equivalent result of the one defined for Kevzara would mean a positive outcome in out trial with a very low p-value.
But the main hurdle is still there: demonstrate clinical outcomes. I am sure we will pass the test wit flying colors.
You all have a great $3.69 SP week-end, feel free to "review" your account as often as you like
Not only they got an adaptive trial but in P2 the primary end point was the lowering by inflammation as measured by C-reactive protein (CRP). As we know, Kevzara is an anti-inflammatory drug (interleukin-6 (IL-6) receptor antibody) used for moderately to severely active rheumatoid arthritis. Basically, they told Regeneron: please show us that you can reduce inflammation. Is like asking CYDY, please show us that you can show occupancy of CCR5.
In any case, the results for mild to moderate where disappointing (maybe because the levels of IL-6 are lower for this condition), as where the results for 200mg in the “critical” group.
Only results for 400mg in the “critical” cohort stuck to the wall.
So, what can we learn? Well, the 200mg group showed a very similar response as far as % of change in baseline CRP: -77% (200mg) vs -%79 (-400mg) and, yet, the death rate was higher than for placebo: 36% vs 27%.
That is, measurements of the primary end point did not translate into clinical outcomes.
Frankly, I would be worried about the results of P3 with 400mg as the correlation does not seem well stablished. The clinical improvement for 200 mg was 51% vs 59% for the 400 mg arm (41% placebo). So, apart from the reduction of IL-6 in measurements carried out by Dr. Patterson and the reduction of CRP in those made by Dr. Yang in our patients at Montefiore we will need to show clinical results (as our IND patients have been demonstrating).
Another lesson for us is that they (FDA + REGENERON-SANOFI) defined “Clinical improvement” as a 2 point improvement on a 7-point scale (1) death; 2) hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4) hospitalized, requiring supplemental oxygen; 5) hospitalized, not requiring supplemental oxygen – requiring ongoing medical care (COVID-19 related or otherwise); 6) hospitalized, not requiring supplemental oxygen – no longer requires ongoing medical care; 7) discharged from hospital.).
This translates to 1.14 improvement in a 4-point scale.
The good news is that for us, such a difference for the means of our trial should likely yield a very small p (if FDA keeps consistency). So, an equivalent result of the one defined for Kevzara would mean a positive outcome in out trial with a very low p-value.
But the main hurdle is still there: demonstrate clinical outcomes. I am sure we will pass the test wit flying colors.
You all have a great $3.69 SP week-end, feel free to "review" your account as often as you like
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