“More is not necessarily better in repeat dose trials.”
Meddic, I agree. That’s why I’m betting we will hear about Bavi’s adaptive immune response on Oct 30 even if the 12-week wait has been finished only for the 0.3 mg and 1.0 mg cohorts, i.e. the first and second cohorts of the repeat dose study.
There is no waiting period required between cohorts in the current 1b study and we know the first cohort completed infusions in late June. Thus, we can be fairly confident the second cohort of the 1b repeat dose study finished its two-week infusion period by late July, which means the 12-week wait finishes for this second cohort before Oct 30. This second 1b cohort received a total of 4 mg/kg of Bavi in four infusions spread over two weeks at 1 mg per infusion. The big point is not the total dose was 4 mg, but as Meddic points out each patient gets four turbo charges of his immune system, with each charge happening just after all traces of Bavi from the last charge have cleared his system.
SK confirmed on July 14 that they are seeing some evidence of an adaptive immune response in humans after a single turbo charging event/dose:
“You seem to have some initial direct AV activity, and then something that really takes place several days later that hopefully can lead to longer-term effects.”
Well if the “something that really takes place several days later that hopefully can lead to longer-term effects” is already evident after a single turbo charging event/dose, what are the chances this “something” will be magnified when the immune system is hit with four consecutive turbo charging events?
That’s the point Meddic is focusing on. That’s the really big question.
A while back on this Board we had a discussion of whether we needed to see a 2 log, 3 log or 4 log reduction in HCV viral load to be in the game. For me to start popping Champagne, all I need to hear on Oct 30 is that the “something that really takes place several days later” did indeed have “longer-term effects” at the end of 12 weeks.
As Jazz keeps pointing out, we have a blockbuster on our hands if the “longer-term effects” (i.e. an adaptive immune response) is occurring regardless of whether the current 1b protocol produces a log 2, log 3 or log 4 reduction. If adaptive immunity is happening, our novel MOA will have been proven and it will be just a short time to find the right mono-therapy or combo-therapy protocol to achieve a permanent cure of most AV and AC diseases.
Remember, however, SK said only that he was seeing “Something … that HOPEFULLY can lead to longer-term effects.” So what are the odds we will see this “longer-term effect” at the end of 12 weeks following repeat dosing. To answer this question the Company gave us a huge clue in the June 7 PR. Be still for 15 seconds and think about the implications of this June 7 statement:
“Bavituximab also showed signs of durable anti-viral activity after a single dose, with some subjects achieving a greater than 80% (0.7 log) reduction in viral load by day four and maintaining a greater than 60% reduction in serum HCV levels up through the end of the study at week 12.”
Bottom Line: If the above level of “durable anti-viral activity” was achieved with a single immune system turbo charging event, what level of durable activity would result from four consecutive turbo charging events?
We should get more clues at the CC on Sept 11, but for sure we'll know the answer on Oct 30. :) :)
All IMO
