Misiu,
Yes, agree. The problem was that the HAART was suspended in some cases before Lero had "fully" taken charge (so to speak).
The problem was (as trding discovered and pointed out) that the half-life was wrongly assumed as 3.5 days. The net result is that the overlap was incorrectly calculated: “treatment Phase with the one-week overlap of existing retroviral regimen and PRO 140 at the beginning of the study treatment”.
The higher the dosage, the longer the half-live.
Now, if 3.5 days where used and the overlap was 1 week we have that only two half-lives where used with an already wrong duration half-live !!!
Now, let’s assume that the REAL half-life is 10 days for 700 mg (maybe still short but let’s assume) and we use 2 half-lives for the time it takes to reach full dose we have 2 X 10 days= 20 days (app 3 weeks). This is what was used with the 525 and 700mg before HAART was suspended (likely resulting in lower failures). This will work better for the 525mg dose than for the 700 mg one (remember, the higher the doses, the longer it takes).
It would be interesting to see what will be decided for the mono trial, IMHO occupancy will be the answer for dosage and overlap. The problem is that this will make the trial very complicated and, worse, lengthy as now we will be talking on effectivity vs occupancy and the FDA will want this earth and the next one worth of data … .
Instead, I would go for a high dosage (700 mg) and a good overlap (4 weeks). One or two weeks more in overlap will reduce the first 10 weeks failures dramatically; AND occupancy test in parallel to support (only support) the results.
I think that, down-the-road the doses will be decided on an individual basis with density and occupancy tests carried out frequently … but shhhhhhhhhh, don't tell the FDA. They have given us the roundabout for too long now.
We deserve a fast, trouble-free Mono approval.
Quote:Good results are when viral load is not going up when HAART is stopped and patient is only on Leronlimab
Yes, agree. The problem was that the HAART was suspended in some cases before Lero had "fully" taken charge (so to speak).
The problem was (as trding discovered and pointed out) that the half-life was wrongly assumed as 3.5 days. The net result is that the overlap was incorrectly calculated: “treatment Phase with the one-week overlap of existing retroviral regimen and PRO 140 at the beginning of the study treatment”.
The higher the dosage, the longer the half-live.
Now, if 3.5 days where used and the overlap was 1 week we have that only two half-lives where used with an already wrong duration half-live !!!
Now, let’s assume that the REAL half-life is 10 days for 700 mg (maybe still short but let’s assume) and we use 2 half-lives for the time it takes to reach full dose we have 2 X 10 days= 20 days (app 3 weeks). This is what was used with the 525 and 700mg before HAART was suspended (likely resulting in lower failures). This will work better for the 525mg dose than for the 700 mg one (remember, the higher the doses, the longer it takes).
It would be interesting to see what will be decided for the mono trial, IMHO occupancy will be the answer for dosage and overlap. The problem is that this will make the trial very complicated and, worse, lengthy as now we will be talking on effectivity vs occupancy and the FDA will want this earth and the next one worth of data … .
Instead, I would go for a high dosage (700 mg) and a good overlap (4 weeks). One or two weeks more in overlap will reduce the first 10 weeks failures dramatically; AND occupancy test in parallel to support (only support) the results.
I think that, down-the-road the doses will be decided on an individual basis with density and occupancy tests carried out frequently … but shhhhhhhhhh, don't tell the FDA. They have given us the roundabout for too long now.
We deserve a fast, trouble-free Mono approval.
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