In your paragraph here: "The severe to critical trial also did not meet its primary endpoint — considering all patients the difference in Day 28 mortality between leronlimab and placebo was not statistically significant (N=384, 50/50 split, p > 0.05)." that study was NOT a 50/50 split (eg a 1:1 treatment to placebo) but rather a 2:1 Treatment-to-Placebo. I don't know the numbers in each group, but I'm sure you can find them quickly. The reason why this study did not hit its endpoint was because in the 2:1 trial design it was a fairly small n for the placebo group, and just by chance because of the small n there were proportionally younger patients in the placebo with more elderly (>65) in the treatment arm, which skewed the mortality towards the treatment group. In the end for the whole data set at day 28 the mortality benefit was ONLY 6% over placebo (24% survival in treatment vs 19% survival in placebo) -- but even this positive 6% was not statistically significant endpoint because of the small n overall. ... So, two problems: small study size (n < 400) and a just by chance enrollment of more elderly to the treatment arm. This caused them to miss the primary endpoint, but anyone looking at all the data in whole (CD10 + CD12 + all eINDs + HIV safety data) would conclude that leronlimab should be considered for emergency use now given the present emergency situation with a continuation of data collection.
One correction: leronlimab is an immunomodulators, NOT an immunosuppressant. Big difference. The downside of immunosuppressants is they increase the risk of secondary infections. Leronlimab, on the other hand, "Leronlimab restored CD8 T-cells and increased Granzyme A to better clear virally infected cells. It also inhibits Treg cells and repolarizes macrophages which both enhance the immune response against infected cells." (quoting Dr. Bruce Patterson). So leronlimab does indeed help reduce blood viral load.
In your paragraph here: "The severe to critical trial also did not meet its primary endpoint — considering all patients the difference in Day 28 mortality between leronlimab and placebo was not statistically significant (N=384, 50/50 split, p > 0.05)." that study was NOT a 50/50 split (eg a 1:1 treatment to placebo) but rather a 2:1 Treatment-to-Placebo. I don't know the numbers in each group, but I'm sure you can find them quickly. The reason why this study did not hit its endpoint was because in the 2:1 trial design it was a fairly small n for the placebo group, and just by chance because of the small n there were proportionally younger patients in the placebo with more elderly (>65) in the treatment arm, which skewed the mortality towards the treatment group. In the end for the whole data set at day 28 the mortality benefit was ONLY 6% over placebo (24% survival in treatment vs 19% survival in placebo) -- but even this positive 6% was not statistically significant endpoint because of the small n overall. ... So, two problems: small study size (n < 400) and a just by chance enrollment of more elderly to the treatment arm. This caused them to miss the primary endpoint, but anyone looking at all the data in whole (CD10 + CD12 + all eINDs + HIV safety data) would conclude that leronlimab should be considered for emergency use now given the present emergency situation with a continuation of data collection.
One correction: leronlimab is an immunomodulators, NOT an immunosuppressant. Big difference. The downside of immunosuppressants is they increase the risk of secondary infections. Leronlimab, on the other hand, "Leronlimab restored CD8 T-cells and increased Granzyme A to better clear virally infected cells. It also inhibits Treg cells and repolarizes macrophages which both enhance the immune response against infected cells." (quoting Dr. Bruce Patterson). So leronlimab does indeed help reduce blood viral load.
Really thorough, thoughtful article. Great work!!