"It's very different to observe differences in clinically determined subtypes which are known to be different outside the context of the trial."
That makes sense to me, and I was hoping that is how the FDA sees it. But I don't know if the CI's responses even fit that description. I don't know if there is an identifiable subgroup for their 15% or 25% of patients that respond. And again, if less than 50% of patients respond, you don't get any improvement in median OS. The improvement in the mean could be huge, but the improvement in the media would be 0. While obviously, if there is a huge improvement in the mean, the drug should be approved, as it was for the CI's. I think the game is changing, though maybe there has always been recognition of these issues, and proper means to deal with them. The level of efficacy for the Phase 1, Phase 2a methylated mesenchymal patients appears to be similar to that of the CI's. A similar percentage of patients with benefit, and a similar level of benefit.
Many do not trust that early, open label, DCVax-L data, as presented, and I don't blame them, but if the phase 3 does prove to resemble the mature phase 1, phase 2a charts that LL presented in that recent lecture, then DCVax-L efficacy is similar to the checkpoint inhibitors.
The data actually showed what may prove to be a cure for about half of the mesenchymals. Clinicians can not use the word cure, but I can. I am assuming that the "about half" is the methylated "about half". If so, and this level of efficacy proves out, then you could argue that DCVax-L is more valuable than the checkpoint inhibitors for 2 reasons: 1) It does not have the horrible side effects that can come from checkpoint inhibitors. 2) It may be possible to identify which 20% of patients will benefit from DCVax-L prior to surgery, allowing other therapies from NWBO or other companies to be trialed for the complement of patients. That is a big deal.
Flipper and Doc Logic and others believe one of the recent studies may indicate a good way to identify patients that will respond to DCVax-L prior to surgery by examining the lymphocytes in the blood to determine whether some immune response to the tumor has begun. This would not necessarily be along known subgroup lines... but again, the CI's were approved, possibly with no defined subgroup for the 15% to 25% response. This initial tumor response, prior to DCVax-L administration, is apparently not strong enough to stop the cancer, but the response indicates a healthy immune system and the existence of mutant antigen targets, making the patient a good candidate for DCVax-L.
And again, Flipper recently provided an example of a CI being approved based on a relatively small phase 2. Not tiny, but small compared to the DCVax-L trial. Flipper and others have also shown a recent case where a CI trial received approval from the FDA without any request from the sponsor.
