Something on the Yahoo board I must address.
There are 2 things on the Yahoo board by questionable posters that seem like a transparent big pharma line of attack.
1. Someone posed the question….What if all the 66 events were deaths?
2. Someone else stated that IMUC posted a letter today from the FDA that stated the FDA (from way back in 2011) would not approve a biologic license application with PFS as the primary endpoint.
IMHO, these 2 taken together are the last desperate gasps of big pharma trying to slow or detour NWBO from demonstrating success while big pharma catches up.
Please bare with me.
The first question above dealing with the 66 initial events possibly being deaths is patently absurd. I'll talk about that more later, but the reason this inane question is raised is to hit at the letter from the FDA to IMUC back in 2011. You see, even though I've previously posted about the FDA moving toward greater acceptance of PFS (Europe accepted it many years ago) as a primary endpoint based upon the obvious cruelty an overall survival endpoint would place upon patients in a GBM trial study, in addition to the inhuman FDA surrender that this would slow research to a snail's pace; the big pharma argument is that that 'death is (of course) the real thing these treatments are meant to avoid, and if you don't look directly at OS as the primary endpoint (so their false argument goes) then you are really going to approve drugs that will not work as often as not.'
Read that last paragraph again. That is their argument. It is based upon an initial extreme and statistically impossible precursor, then followed with a rational sounding but absurd result.
This is a war folks, and this is where it is heading to. I didn't realize it until recently.
Let's step back and look at NWBO and what they are attempting to do. NWBO is attempting to conduct a phase 3 trial with PFS as their primary endpoint, and Overall survival as a secondary endpoint. NWBO introduced a crossover arm (for humanitarian purposes) so that the actual "control arm" for overall survival comparison will need to be something closer to the average statistics from S.O.C. findings over this decade. So, the only OS control, within the present trial data itself, to judge the treatment arm against…. is the Crossover arm. Therefore, NWBO must really use recent historical data for OS (overall survival). If DCVAX-L's data turns out like it did in Phase 1, EVEN THE PFS (Progression Free Survival), FROM THE DCVAX-L TREATMENT GROUP, WILL SIGNIFICANTLY STATISTICALLY OUTPERFORM THE HISTORICAL OS (OVERALL SURVIVAL) OF A STANDARD OF CARE GROUP!!!!
Read that last sentence again.
So now, imagine you're a slimy big pharma company that wants to give the FDA (perhaps some on their private payroll) an excuse to still deny a biologic license application to NWBO DCVAX-L (by making them do a second 4-7 year phase 3 GBM follow up study).
Imagine the current DCVAX-L Phase 3 results are actually out, and they really show that the primary PFS endpoint for DCVAX was easily met by the treatment group, and in fact, even the PFS (Progression Free Survival) in the treatment group statistically beat the "Recent Historical Overall survival for S.O.C. patients that used the Stupps protocol with and including total resection."
How do you -- a slimy big pharma company -- stop that drug (DCVAX-L) from getting approved????
You make a ridiculous but straight faced argument that gives some (not all) on the FDA a face saving but inane and statistically impossible argument in order to deny DCVAX-L approval.
What's your argument??
Slimy big pharma and a few FDA grunts' phony but straight faced argument:
"Well Linda, honey, I see you got statistical significance for PFS (Progression Free Survival)….congratulations (golf clap)….but…oh dear, how do I say this without hurting your feelings….didn't you realize that very statistically significant improvement in PFS does not necessarily indicate any improvement at all in OS (overall Survival)???? Why some big pharma companies just recently conveniently sponsored an article that proves just that -- using a few reviews.
Linda Responds: "Are you blind? Even our PFS (Progression Free Furvival) beat the recent historical average for OS (Overall Survival)."
Slimy big guys: "Oh….'recent historical average' you say….tsk tsk….that does not sound very much like it came from a control arm in your phase 3 study….that's not very scientific Linda….."
Linda Responds: "Our treatment arm beat our own crossover arm as well, and this demonstrates delayed treatment can kill."
Slimy Big Guys: "Are you sure about that Linda?" What if you had no crossover arm? What if your control arm had lived longer than the crossover stats you have right now? What if….Linda honey….what if the control arm would have even outlived the treatment arm, and the deaths were all going to happen earlier in the treatment arm rather than the control arm….I guess we just can't know dear….oh such a shame….you'll have to do another study….back to the drawing board as they say….and all the patients that will die because you can't prove what you already know -- shhhhh -- and we know too dear….DCVAX-L really is a miracle."
Linda response: "Look, we beat the primary endpoint for PFS by an incredible amount, and that even exceeded Historical OS by an incredible amount, and our Treatment OS beat the historical OS by more than double….there is no way in hell the FDA will look at this improvement as statistically insignificant. There is no way they will force more people to die, when they know for certain we have just given significantly extended life…and in some case, a cure to these patients."
Slimy Big Guys: "Oh, but Linda, you used patients with total resections and no sign of measurable tumor progression after radiation and chemo….but before starting your little biological treatment. So, that has never been done quite that way before, maybe the FDA will rule that it all could have been these perfect surgery candidates you selected and further that they did not have aggressive tumors when you started treatment. Maybe their long lives are really due to great surgeons plus timid GBM cancers."
Linda: "You know better than that, there are many large studies with hundreds of patients on total resections plus chemo and radiation….they live only a couple months longer at best, and even accounting for no tumor progression at the start of DCVAX-L treatment, they still can die in 6.9 months median survival. Roche just had these results with Avastin in their control arm."
Slimy big Guys: "They didn't select for non-progression when they started treatment…."
Linda: "Yes they did, and they conducted total resections….and still they only got 6.9 months median survival…."
Slimy Big Guys" "Well that's their control arm, you can't use it or anyone else's to prove your point….you must do a second phase three….this time without a compassionate crossover arm, and you are just gonna have to let a lot of people die in your control arm to prove your point….oh…such a shame…so much time wasted…so many lives you could be saving….if only you hadn't been so soft hearted…."
Linda: "That's the most inane argument I've ever heard, the majority of clear thinking people at the FDA will see through your bald faced lies and red herrings…."
Slimy Big Guys: "Hmm are you talking about Joey Boy, Little Frankie and Gold digging Gabe?
Linda: No…I'm talking about the FDA…..
Slimy Big Guys: "So are we…."
This makes NWBO's Marnix Bosch's presentation at the end of January that much more relevant.
