Replies to post #237471 on NorthWest Biotherapeutics Inc (NWBO)

[Umibe5690]

Dr. Bala:

I suspect that when this long standing trial was commenced, PFS, as a surrogate for OS, was selected as the primary end-point. From rad/chemo trials it was recognised that PFS was a good correlative surrogate for OS which would serve to shorten the trial. However, considering immunological approaches, PFS as a surrogate for OS may not be a good correlative. The gold standard is still OS. Due to the length of the DC VAX trial, it now has enough OS data so that the PFS surrogate has less significance than it originally had. And as I have mentioned, even though PFS eventing may not significantly surpass that of SOC, it is within the realm of possibility that the vaccine dramatically slows progression rate such that patients live longer with a better QOL. Such a result, if part of the SAP protocol, would nullify any shortfall in meeting the original PFS end-point. This would be well understood by the medical and regulatory communities--at least one would suspect. It may be less well understood by the short-attentioned general investment community which would likely focus on a failure to meet a trial primary end-point. Thus, although strong data is important, its mode of presentation is also important especially for the investment community. This is where Innes who has experience as a market pro will earn his keep. I believe that is why he was hired. It is critical that top line presentation has a significant and sustaining effect upon the share price. JMHO.

[meirluc]

1. I need to wait for the published results on mPFS. It doesn’t make sense to me to have a vast improvement in mOS without a corresponding improvement in mPFS. If the GBM dynamics under DCVax-L is according to the model you suggested, then mOS should be the primary and possibly the only endpoint, imo. The team should have a dynamicist who should model the progression under DCVax-L administration. It is not essential, but at least that would be interesting to me.

There is a possibility that the unblinded treatment mPFS and mOS will be statistically significantly better than the mPFS and mOS of the placebo/control arm. However, I will not bet on it. Remember that the blinded and blended post surgical mOS was only 23.1 months and we have to subtract about 3 months from that to obtain the post enrollment mOS. That is not a great result and may also be reflected by the mPFS of treatment vs. placebo/control which may or may not show SS differences favoring the treatment arm.

Having said that, there is little doubt in my mind that 25%PFS and 25%OS for the treatment arm are home runs in that they will be impressive on their own as well as significantly better than placebo/control.

Remember that according to the report of February 2017, roughly 36 months after the midpoint surgery and 33 months after midpoint enrollment, about 25% of the trial was still PFS. I have not come across trials with a similar GBM population where 1/4 of the trial still demonstrated PFS after 33 months post enrollment. I will also not be surprised if 25% of the treatment arm will still be alive beyond 4 years and more than 20% survive past the 5 year timeline.

I believe that in this trial it is all about the tail and the mOS and mPFS will not have great significance. The importance of a long thick surviving tail may have forced NWBO to compose a new, hitherto unconventional SAP which may explain why it has been taking over 6 months to do just that.