I wholeheartedly agree that we deserve the EUA for Mild to moderate. More so when the bar has been lowered so much (please see Remdesivir).
But we are not GILD. We are just a small company with a very good drug. It should not mater but it does.
So, what would an impartial and efficient agency do ??? Well, study carefully the secondary outcomes:
We know we barely missed the primary outcome (according to NP). We know we succeeded statistically In point 2 of Secondary outcomes (NEWS2 Per Patient Population p<0.03 and p<0.02 days 3 and day 14 respectively). We probably did well in point 1 TTCR, however I have no idea if this was statistically significant.
Point 3 is also probably good as is part of the NEWS2 measurement (actually there are two items, Scale 1 and scale 2 for SpO2 and BOTH score points in NEWS2). Point 5 is probably good as there were much less SAEs in Leronlimab than in Placebo. The same can be said for 5-11.
However, imo, the KEY part are other outcome measures:
The patients were being monitored with blood-work. If I am the FDA and somebody shows me in charts a comparison between placebo and Leronlimab cohorts for the first days and I see a marked difference, I don’t need further proof.
Say, for example, the CD4/CD8 ratio goes down to normal levels more rapidly with LL than in placebo… or the cytokine/chemokine levels go down dramatically one does not have to be a genius to conclude that the drug is working and the statistically-significant clinical outcomes of NEWS2 can be explained by these numbers. Period.
My point: I am putting my money in the rest of the supporting evidence to convince the FDA that Leronlimab works.
Now, if we don’t get a positive response there are three possibilities:
-- Leronlimab simply does not work for M2M COVID-19
-- The data is good but not conclusive (P3 necessary), or, in other words: Leronlimab works but is not the last frozen coca-cola in the dessert.
-- The FDA is corrupt and, in spite of obvious benefit, will slow-walk us until GILD and/or other FDA-contributing BPs launch their less efficacious products.
We will know more on Wednesday.
But we are not GILD. We are just a small company with a very good drug. It should not mater but it does.
So, what would an impartial and efficient agency do ??? Well, study carefully the secondary outcomes:
Quote:1. Time to clinical resolution (TTCR) [ Time Frame: Day 14 ]
2. Change from baseline in National Early Warning Score 2 (NEWS2) [ Time Frame: Days 3, 7, and 14 ]
This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). Higher scores mean a worse outcome.
3. Change from baseline in pulse oxygen saturation (SpO2) [ Time Frame: Days 3, 7, and 14 ]
4. Change from baseline in the patient's health status on a 7-category ordinal scale [ Time Frame: Days 3, 7, and 14 ]
A 7-category ordinal scale of patient health status ranges from: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Lower scores mean a worse outcome.
5. Incidence of hospitalization [ Time Frame: Day 14 ]
6. Duration (days) of hospitalization [ Time Frame: Day 14 ]
7. Incidence of mechanical ventilation supply [ Time Frame: Day 14 ]
8. Duration (days) of mechanical ventilation supply [ Time Frame: Day 14 ]
9. Incidence of oxygen use [ Time Frame: Day 14 ]
10. Duration (days) of oxygen use [ Time Frame: Day 14 ]
11. Mortality rate [ Time Frame: Day 14 ]
12. Time to return to normal activity [ Time Frame: Day 14 ]
We know we barely missed the primary outcome (according to NP). We know we succeeded statistically In point 2 of Secondary outcomes (NEWS2 Per Patient Population p<0.03 and p<0.02 days 3 and day 14 respectively). We probably did well in point 1 TTCR, however I have no idea if this was statistically significant.
Point 3 is also probably good as is part of the NEWS2 measurement (actually there are two items, Scale 1 and scale 2 for SpO2 and BOTH score points in NEWS2). Point 5 is probably good as there were much less SAEs in Leronlimab than in Placebo. The same can be said for 5-11.
However, imo, the KEY part are other outcome measures:
Quote:1. Change in size of lesion area by chest radiograph or CT [ Time Frame: Day 14 ]
2. Change from baseline in serum cytokine and chemokine levels [ Time Frame: Days 3, 7, and 14 ]
3. Change from baseline in CCR5 receptor occupancy levels for Tregs and macrophages [ Time Frame: Days 3, 7, and 14 ]
4. Change from baseline in CD3+, CD4+ and CD8+ T cell count [ Time Frame: Days 3, 7, and 14 ]
The patients were being monitored with blood-work. If I am the FDA and somebody shows me in charts a comparison between placebo and Leronlimab cohorts for the first days and I see a marked difference, I don’t need further proof.
Say, for example, the CD4/CD8 ratio goes down to normal levels more rapidly with LL than in placebo… or the cytokine/chemokine levels go down dramatically one does not have to be a genius to conclude that the drug is working and the statistically-significant clinical outcomes of NEWS2 can be explained by these numbers. Period.
My point: I am putting my money in the rest of the supporting evidence to convince the FDA that Leronlimab works.
Now, if we don’t get a positive response there are three possibilities:
-- Leronlimab simply does not work for M2M COVID-19
-- The data is good but not conclusive (P3 necessary), or, in other words: Leronlimab works but is not the last frozen coca-cola in the dessert.
-- The FDA is corrupt and, in spite of obvious benefit, will slow-walk us until GILD and/or other FDA-contributing BPs launch their less efficacious products.
We will know more on Wednesday.
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