"The company obtained approval from the US FDA" …. Are you suggesting that the FDA did not approve of these enhancements that NWBio PR'd they did approve?” - Senti
Yes, that is what I am suggesting. That PR is very misleading. This trial does not have a SPA. The changes may have been “approved” by the FDA in the sense that they will allow the trial to proceed, but that is a big difference from the FDA approving that the trial design is sufficient to form the basis of a regulatory submission for licensing. Again, there is no SPA here (though the PR implies one). The FDA allows “wide latitude” in clinical trial design:
“Even though FDA offers extensive technical assistance, drug developers are not required to take FDA’s suggestions. As long as clinical trials are thoughtfully designed, reflect what developers know about a product, safeguard participants, and otherwise meet Federal standards, FDA allows wide latitude in clinical trial design.”
“Are you suggesting that if this already proven safe product doesn't achieve 4 months PFS over the control group... it won't be approved by the FDA?”-Senti
I think you mistyped that. If it doesn't achieve 4 month PFS benefit it is not going to be approved based on PFS. If it DOES achieve a 4 month benefit in PFS that is certainly no guarantee of approval. It will be, as they say, a matter for review. However, you didn't answer my question: Why didn't Roche file in nGBM after achieving a 4.4 month PFS advantage?
“Are you suggesting that even if DCVax-L shows an improvement of 4 months PFS, it won't show an improvement in OS because AVAglio didn't? “ - Senti
Many trials have shown an effect on a surrogate endpoint (PFS) without showing an effect on clinical benefit (OS). AVAGlio was simply a recent relevant example in the same indication. (And, make no mistake, OS will be analyzed ITT as in AVAGlio. Not censoring at x-over or RPSFT)
“We'll both have to wait and see what the P3 demonstrates.“ - Senti
"You could start checking by looking at IMUC's results in a 167 patient GBM trial."
a good start, but realize that their Ph2 didnt reassess progression status at randomization (their Ph3 will).
And of course, NWBO's trial DOES assess progression status immediately prior to randomization. It wouldn't be a surprise to see NWBO's control arm outperform IMUC's control arm.
"Do you believe they need to achieve more than what the FDA has already agreed to for PFS as the primary endpoint to be accepted?"
What exactly do you think the FDA has "agreed to"? This trial does not have a SPA.
The AVAGLio trial in nGBM demonstrated a 4.4 month PFS benefit (p of 0.0001). Roche didn't even bother trying to file a BLA. Do you know why? (Hint: they did have a SPA and clearly knew what the FDA wanted to see)
6. BRIEF DESCRIPTION OF MANUFACTURING PROCESS FOR PLACEBO
(Both DCVax-L and placebo will be manufactured for all patients undergoing leukapheresis.)
6.1.1. MNC Preparation
Peripheral blood mononuclear cells are isolated by leukapheresis from the patient before treatment begins. MNC are purified by density gradient centrifugation, and cryopreserved for shipment to the clinical site for patients who are randomized to the placebo cohort.