IMO it is correct to point out that the bar is set very low with remdesivir as the only approved antiviral to treat CV19 in the U.S.
Some of the confusion regarding remdesivir is due to its positive lab results in vitro versus its less than stellar effectiveness in treating CV19 patients. Farrell does a great job in explaining this in post #69701 dated 6/7/21. Remdesivir is a prodrug that must be converted to its active metabolite and is toxic at high dosage versus Brilacidin’s multiple mechanisms of action not needing to go through this conversion and being more effective as it disables the CV19 virus at safe levels.
When lab testing was done by GMU they tested Brilacidin as both a standalone drug and in combination with Remdesivir on human tissue. Brilacidin alone showed a 97% effectiveness in a human lung epithelial cell line (6/17/20 PR) and a near 100% effectiveness in a combination with remdesivir (9/15/20 PR). Brilacidin also attained a very high Selectivity Index of 426 (10/30/21 PR) as a proof point of both safety and antiviral effectiveness.
The end points of success in the Remdesivir human trials were modified by the FDA/ Fauci etc. and approved based on reduced hospital stays versus the original hope that it would show improved mortality rates and viral load reduction.
I believe Leo worked very closely with the FDA in the design and with every detail of the B-CV19 phase 2 study to insure that a successful result in the trial would lead to eventual approval of Brilacidin. We have not seen details on what the specifics are in regards to the trial design but it is likely that remdesivir was the major drug used as the SOC for U.S. patients as it is the only therapeutic antiviral approved in the U.S. to treat CV19. Speculation is that favipiravir was the used as the SOC for the Russian patients in the trial.
The B-CV19 trial was set up so that half of the patients were treated with SOC only and half of them treated with Brilacidin PLUS SOC. It is very likely that the U.S. based patients getting Brilacidin will show improvement which will prove that the combination of Brilacidin plus Remdesivir is superior to Remdesivir alone. My belief is that Brilacidin does not need Remdesivir to be successful but the U.S. portion of the trial will not scientifically prove that point even though common sense IMO does. If it takes a combination treatment designation to get Brilacidin’s approval process expedited in the U.S., so be it.
If the Brilacidin treated patients in the Russian portion of the trial show improvements over a different SOC it will be an additional proof point that Brilacidin is likely a very effective standalone treatment for CV19. The WHO, Russia and many other countries do not recognize remdesivir as a viable treatment so we may initially see Brilacidin as a combo therapy in the U.S. and possibly as a standalone treatment overseas.
I believe that if Brilacidin proves to be successful in the phase2 B-CV19 human trial it will trigger multiple events including funding from either/both government grants/BP partnerships, EUA for moderate/severe as a combo in US and possibly standalone abroad and an accelerated CV19 phase 3. I also believe that there will be ample funding to quickly develop additional delivery mechanisms such as an inhaler and/or depo which will expand the patient population to include mild/moderate CV19 and as a Broad Spectrum virus treatment.
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In vitro testing results can be vastly different than FDA human trial results. farrell in post #69701 explains “Remdesivir is a prodrug and is converted inside the cell to its active metabolite which is estimated to have an IC 50 of 38um to 231um or 7.7um in other studies, well below that of Brilacidin's IC 50 of .565um. In addition Remdesivir's hepatotoxicity limits higher dosing.” And…
“Fortunately Brilacidin is not limited by these factors.
With its good pharmcokinetics and high SI number it is well distributed throughout the body and kills the virus in the extracellular spaces as well as inside the cells. It was shown in the Viruses publication to block entry of Covid19 in the cells. And, computer modeling suggests it can disrupts the viral M-protein of Covid19 to prevent viral replication.
These multiple mechanisms of action, high SI number and safety all should make Brilacidin a superior antiviral, but also be active against Covid variants. It should make viral resistance much less likely.”
Some of the confusion regarding remdesivir is due to its positive lab results in vitro versus its less than stellar effectiveness in treating CV19 patients. Farrell does a great job in explaining this in post #69701 dated 6/7/21. Remdesivir is a prodrug that must be converted to its active metabolite and is toxic at high dosage versus Brilacidin’s multiple mechanisms of action not needing to go through this conversion and being more effective as it disables the CV19 virus at safe levels.
When lab testing was done by GMU they tested Brilacidin as both a standalone drug and in combination with Remdesivir on human tissue. Brilacidin alone showed a 97% effectiveness in a human lung epithelial cell line (6/17/20 PR) and a near 100% effectiveness in a combination with remdesivir (9/15/20 PR). Brilacidin also attained a very high Selectivity Index of 426 (10/30/21 PR) as a proof point of both safety and antiviral effectiveness.
The end points of success in the Remdesivir human trials were modified by the FDA/ Fauci etc. and approved based on reduced hospital stays versus the original hope that it would show improved mortality rates and viral load reduction.
I believe Leo worked very closely with the FDA in the design and with every detail of the B-CV19 phase 2 study to insure that a successful result in the trial would lead to eventual approval of Brilacidin. We have not seen details on what the specifics are in regards to the trial design but it is likely that remdesivir was the major drug used as the SOC for U.S. patients as it is the only therapeutic antiviral approved in the U.S. to treat CV19. Speculation is that favipiravir was the used as the SOC for the Russian patients in the trial.
The B-CV19 trial was set up so that half of the patients were treated with SOC only and half of them treated with Brilacidin PLUS SOC. It is very likely that the U.S. based patients getting Brilacidin will show improvement which will prove that the combination of Brilacidin plus Remdesivir is superior to Remdesivir alone. My belief is that Brilacidin does not need Remdesivir to be successful but the U.S. portion of the trial will not scientifically prove that point even though common sense IMO does. If it takes a combination treatment designation to get Brilacidin’s approval process expedited in the U.S., so be it.
If the Brilacidin treated patients in the Russian portion of the trial show improvements over a different SOC it will be an additional proof point that Brilacidin is likely a very effective standalone treatment for CV19. The WHO, Russia and many other countries do not recognize remdesivir as a viable treatment so we may initially see Brilacidin as a combo therapy in the U.S. and possibly as a standalone treatment overseas.
I believe that if Brilacidin proves to be successful in the phase2 B-CV19 human trial it will trigger multiple events including funding from either/both government grants/BP partnerships, EUA for moderate/severe as a combo in US and possibly standalone abroad and an accelerated CV19 phase 3. I also believe that there will be ample funding to quickly develop additional delivery mechanisms such as an inhaler and/or depo which will expand the patient population to include mild/moderate CV19 and as a Broad Spectrum virus treatment.
======================================================
In vitro testing results can be vastly different than FDA human trial results. farrell in post #69701 explains “Remdesivir is a prodrug and is converted inside the cell to its active metabolite which is estimated to have an IC 50 of 38um to 231um or 7.7um in other studies, well below that of Brilacidin's IC 50 of .565um. In addition Remdesivir's hepatotoxicity limits higher dosing.” And…
“Fortunately Brilacidin is not limited by these factors.
With its good pharmcokinetics and high SI number it is well distributed throughout the body and kills the virus in the extracellular spaces as well as inside the cells. It was shown in the Viruses publication to block entry of Covid19 in the cells. And, computer modeling suggests it can disrupts the viral M-protein of Covid19 to prevent viral replication.
These multiple mechanisms of action, high SI number and safety all should make Brilacidin a superior antiviral, but also be active against Covid variants. It should make viral resistance much less likely.”
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