Replies to post #439598 on NorthWest Biotherapeutics Inc (NWBO)

[vator]

An event can be progression. Not death alone. So pseudo progression would be considered an event. The vaccine ends up doing what it is intended but considered a failure with the old PFS way of thinking.

[vator]

Based on Sentiment’s statement the logic of it makes little sense. My sense they saw eventing in the control arm but patients were getting better.

[IkeEsq]

I assume 'eventing' referred not to dying but to progressing as a result of psuedoprogression, which appears to be a relapse but is actually a sign that the treatment killed the cancer cells.

[sentiment_stocks]

Progressed… not died.

A pseudoprogression response would be defined as progression by the “dated” criteria used in this trial. The criteria was set back in 2007… and was not designed to look for a pseudoprogression response. Simply if the tumor had returned and grown by a certain small number of centimetres as determined. Y an MRI, the patient was determined to have progressed. However, I suspect, then (as evidenced by many of LL’s statements in her presentations), that many of the same patients that had been diagnosed as having progressed went on to one) have their supposed returned tumor go away; and two) live much longer than one would normally see from a supposed recurrent GBM patient. But if those patients falsely eventing early were the treatment patients, that would “wreak havoc” (to use Dr. Bosch’s own publicly stated words when describing what pseudoprogression can do to a trial) on a trial using PFS as its primary end point.

Of course, the trial’s former secondary endpoint of OS would have been showing much better results, but if the primary end point was failing, any alpha ascribed to the primary would not roll downhill to the secondary, thus compromising a successful outcome for the trial.

A similar situation had happened with the first Dendreon trial for Provenge. I think it was in 2007, and the trial failed its primary endpoint for PFS, and lost all its alpha (there was none left in reserve - while with the DCVax-L trial, I suspect there was a 2/3 split with the old endpoints). So while the Provenge OS would have been stat sig, there was no alpha remaining to measure the OS. So back then, the FDA denied Dendreon’s BLA and told them to run another trial. Which they did… and which on the second round, the FDA approved.