Dr. Bala:
Let me try it another way. The authors of the JTM article could have handled PFS much in the same way as OS was dealt with. For example, they could have averred that under SOC mPFS is historically anywhere between 6~9 months. Blended data shows that mPFS is 13.2 months. There are issues concerning confoundment by pseudo-progression and accordingly, in order to confirm accuracy of this metric, an adjudication will be performed at the end of the trial---or words to that effect. The fact that this was not stated suggests, at least to me, that the blended data was not strong at that point and thus the authors chose not to address PFS.
IMHO, I believe it is possible for patients to live longer by engaging in DC VAX therapy even though PFS is not significantly improved over SOC. I have raised the possibility that immunological therapies take longer to manifest their efficacies vis-a-vis chemo/rad approaches as part of SOC. As time unfolds and the therapeutic effects begin to strongly take hold, PFS eventing may indeed have taken place, however, PFS rate of progression has been slowed and in some cases reduced to zero. Thus, there is an increase in the PFS/OS delta whereby patients are living longer.
The results of the trial need to appeal to basically three constituencies: medical community, the regulatory agencies and the investment community. Although PFS is a primary end-point, there may not be statistical significance or the results may be relatively ambiguous. Failure to meet the primary end-point of the trial may not be fatal and other metrics may show results such that regulatory approvals issue despite the failure to achieve this endpoint. Accordingly, insofar as the medical/regulatory communities are concerned, failure to achieve this end-point may be of lesser significance when considering other factors. However, the investment community thinks much more simply and has a short attention span. The more complex and complicated an explanation may be in addressing PFS within the context of the trial results, Wall Street may understand little but the fact that NWBO, at least technically, failed to achieve this primary end-point. Accordingly, the share price may not significantly increase thus engendering investor concerns of continuing and highly dilutive financings up to ultimate regulatory approvals which may not be around the corner.
Accordingly, the manner of presentation of top-line will be of utmost importance. Of course, this will depend upon the data and the mode of presentation will be made easier in accordance with the strength of the results. With NWBO's history of being very parsimonious with its revelations and concerns with possibly upsetting the FDA and other RAs by revealing too much, top-line presentations may be found wanting, at least by the investment community, which will look upon failure to achieve the primary end-point as a total trial failure.
Strong/clear and easy to understand top-line results, including meeting the primary/secondary end-points, with a statement that NWBO will be filing a reg application--a best case scenario-- will undoubtedly go a long way to insure a sustainable significant increase in the share price. JMHO.
