Iwasadiver:
Thanks very much for your response. After reading acting FDA Director Ned Sharpless' comments, which I found to be highly encouraging, I believe that DC VAX L evaluation will be relatively straight forward and based primarily upon milestones/long tail. I disagree with Dr. Wick's implication that PFS endpoint may be of primary decisional significance due to the confoundment resulting from the cross-over. Dr. Sharpless believes that overall survival is the gold standard. Longevity will be of primary decisional significance IMHO.
In previous posts, I have alluded to the findings published in the JTM especially with respect to M+ and M- and the confusion created by the chart in the iHub MB introduction assigning sub-group categories such as pro-neural to M+ and MES to M-. Methylated MGMT promotor is a rather large sub group which appears to have demonstrated significant survival as compared to control historicals upon a blended basis. M+ appears to be a less aggressive variant than MES which appears to be highly aggressive and with a much diminished SOC survival compared to M+. Due to these differences, I believe that MES and M+ are separate and non-overlapping categories and represent at least two large sub-groupings where DC VAX L would appear to be rather effective especially based upon the Liau/Prins findings wrt MES. M+ comprises almost 45% of the M+/M- total group in the DC VAX L trial population. MES has been estimated to constitute anywhere between 25%~40% of all ndGBM. Dr. Wick has mentioned the fact that therapies, including DC VAX, have shown promise in certain sub-groupings although he has stated that the results published in the JTM wrt to DC VAX L are not helpful in assessing efficacy. On the whole, I did not find Dr. Wick's comments to be negative or unreasonable but rather, bottom-line, a call for unblinding in order to assess efficacy.
An important milestone is, of course, the long tail at OS60 and its composition. It appears that upon a blended assessment of OS for 5 years, there is approximately a derived survival of 20%. Upon unblinding, it is possible that overall Tx could be in a range of 20%~25%. I would guess that the overwhelming majority of the long tail would be composed of M+ survivors and much less MES survivors.
There may be a steep drop-off of MES survivors at say the OS36/48 milestones but never the less notable survival of this group short of OS 60.
Given all this, I feel rather confident that the results will be highly positive on long tail/milestones, PFS will have lesser decisional significance(assuming the the primary end point was not achieved) and noting Dr. Sharpless' remarks wrt glioblastoma, DC VAX L will more likely than not be approved, especially when considering comparisons with Optune and the superior amount of data collected in the DC VAX L trial and milestones beyond 24 months.
I think it is a question of when rather than if approval issues and if the top line is positive as we longs believe, approvals will come sooner rather than later given current regulatory environment leanings. Further, I believe that even though DC VAX L may prove to be more efficacious for certain groupings, the FDA will provide a blanket approval in line with Dr. Ashkan's clinical assessment that the vaccine should be made available to all patients as it works to a greater or lesser extent across all groups. The decision as to whether to use DC VAX L as an adjuvant to current SOC should be a decision reached between patient and physician rather than circumscribed by regulatory fiat. JMHO.
