We are way past the point where negative trial news would come out...
Statements in the last presentation by Dr. John Yu regarding when they expected to reach 32 events and how it was calculated.
John Yu: The number, the anticipation of the 32 events came from a program where the outcome of patients was modeled with 80% power to show a nine-month survival benefit in the experimental group versus the treatment group.
So there were various scenarios that were modeled and we – and thereby gave the expectation of the 32 events to occur in the first quarter. So we’re waiting for those events to come out, and for the DMC to review those events and to let us know once that’s occurred.
John Yu: The assumption was for nine-month survival benefit based on the fact that when you have a small Phase I trial which is expanded to a larger Phase II trial, which is blinded and randomized, the expectation of the delta in survival is generally becomes tighter. And so in order to account for that we used a nine-month survival benefit. So the number of events that we’re waiting for, for the interim results is essentially the 50% of the expected events which is 64 by the end of trial.
John Yu: So there were various scenarios that were modeled and we – and thereby gave the expectation of the 32 events to OCCUR in the first quarter. So we’re waiting for those events to come out, and for the DMC to review those events and to let us know once that’s occurred.
John Yu: We are expecting THAT WE WILL LEARN of the interim analysis RESULT from the DMC, the Data Monitoring Committee in the second quarter.
John Yu: It was based on 18.8 months in the control group and the ADDITIONAL 9 months in the experimental group with a 2:1 ratio of experimental to control patients.
Based on the available data, I calc the point at which we would have been at zero benefit to have been in mid January. That works out to an additional month of advantage about every 8 days or so.
My first thought with the drop yesterday was something leaked about a dilution... I have good bit of skin in the game so no matter what anyone else says - we all get that churn in our stomachs hoping that there is nothing bad leaked about the trial. Naturally I thought - what could be the worst case scenario for the 32nd event – yes the CRO could say stop it, but I think that is highly unlikely because immunotherapy has been demonstrated to be fairly safe with other companies/drugs and this immunotherapy is being ADDED to the SOC – not in the place of it so I find it HIGHLY unlikely that the treatment arm is doing worse than the control arm and I would be willing to bet that the CRO would continue the trial even if they are equal just to see if there is a benefit that will show up more over time. My biggest fear in these type trials is the control arm doing better than the historical norms – so yesterday I modeled a 20.5 month OS for both grps to see where this would put the 32nd event. I got an 80% probability of the 32nd event falling between Jan 27th and Mar 9th and some probability (very low) of it occurring all the way out to the end of Mar.
I really cant see anything leaked about dilution as they have plenty of money to last them well into 2014. Also with the somewhat recent public offering just 4-5 months ago I cannot see them doing another at this point. I think they are smart enough to realize that it would turn off many investors to do another dilution so soon. Also with the pps where it is at the moment it wouldnt make sense as they could wait until a few months before results are announced when the pps will be significanty higher than it is today to do a public offering. If we go another few months 2-3 without the interim being triggered than I could see them waiting until after results are announced. Your second concern of the CRO stopping the trial is extremely small in my opinion. Like you said this drug appears safe (and even if it wasnt 100% safe, we are dealing with gioblastoma so having a few adverse affects wouldnt be a deal breaker) and I agree that even if there was no improvement at interim they would continue to the end. ONTY, ZIOP, CLSN, etc. obviously were not showing benefit at their interim but the trial was not stopped.
Part of the big drop today and yesterday was just overall market sentiment and the fact the most small cap stocks got hammerred. I personally have been leveraging my account by investing in TZA (3X inverse ETF of the Russel 2000) the last few days which have thankfully offset the losses suffered with IMUC this week. Like a few have said earlier maybe it is the MM shaking out the weak hands before good news is announced. Unfortunetly I cant think of any good news that they could be announcing at this time. I would prefer not to hear that the interim has been triggerred and I really hope that they do not partner with anyone at least for the U.S. market.
Anyway a year from now I hope we just see this a small bump in the road. This is a multi billion dollar company in the making and I think we will be well rewarded in due time.
One minor(?) fly ITO.
In the last presentation, the new CEO contradicted , somewhat, Yu's previous statement that the news of the 32nd event would come soon after it occurs. I forget the exact wording but the new CEO said there would be a fair amount of lag bet. that event (32nd) and the announcement. Also 18.8 mo.survival w/SOC, though very generous, could just possibly be short of the actual SR in the control.
I have the transcript in front of me and they seem to be in lock step on that particular point.
Gengos: From the time that the 32 events have been reached and verified to when we receive the recommendation from the DMC, is likely to be several weeks.
Later in the Q&A session John Yu regarding the 32 events projection used a similar/same "takes several weeks" phrase. (see my previous post for the exact verbiage)
I would worry about slightly longer control group survival except that any benefits in the control group should also be showing up equivalently in the trial group.
Additionally, the Phase II vaccination schedule delivers a MUCH higher quantity and frequent dosing of DCs to the patient. I am expecting to see this show up in terms of PFS and OS.