Hungary hippo... the treatment involved with NWBO is a dendritic cell vaccine to treat all solid tumor cancers. They have been in a P3 trial (that evolved from a P2) trial for many, many years. The trial was due to end in 2014, but they instead expanded it. Then it was due to end in 2015, and instead, a screening halt was applied to it. The reason for the screening halt (which was lifted in Feb 2017) was never given but most think it was due, initially, to what appeared to be too many treatment patients eventing earlier than the the control arm patients. The ones that could see that would be the data monitoring committee (DMC) who could view the trial unblinded. Some think the DMC tried to halt the entire trial, but the company persevered claiming that all the patients were living longer, despite the early progression. One should note that the head of the DMC was also working on the scientific advisory board (SAB) of a competing dendritic cell company, and his brother was on the board of directors and SAB of the same company during the entire time, unbeknownst to anyone including NWBO. You can make of that what you will.
Meantime, examining what would ultimately turn out to be pseudo progression (we think), and proving it, appears to have taken about two years, which was when the screening halt was lifted.
Initially it was intended that the randomized trial would end with the primary end point, progression free survival (PFS), and that the company would ask for accelerated approval (AA) based on amazing results. Unfortunately, when one finds pseudo progression has "wreaked havoc" with your PFS results, that makes such an undertaking, well, next to impossible. So... the company opted to wait longer and let the overall all survival (OS) endpoint play out, since everyone was living longer than what is normally seen with GBM. There is also a cross over in this trial whereby when the control patient events, they can cross over to treatment. As a result, about 90% of the patients ended up on treatment.
So... to your question, what is going on here? The trial is finally ended, all the patients have received all their treatments, there was a soft data lock done sometime in the Fall of 2018. Since then, the company has been assembling all the data with the intent to submit for a biologics license approval (BLA) for the treatment. First, though, and while they have been gathering and scrubbing the data (which is what you do in order to submit for a BLA and before you unblind a trial), they have also been finalizing their statistical analysis plan (SAP). Because they have never unblinded the data - remember only the DMC could do that - they can revise the trial as they progress as they are doing so based on a blinded viewpoint. So... when this SAP is completed, they will submit it to the FDA and 3 other regulatory agencies (UK, EU, Canada) for review and approval, or whatever it is that these regulatory agencies (RAs) do with the SAPs. Once the company has that approval or indication that the RAs are okay with the SAP in hand, and once all the data is scrubbed, the data is hard locked and the trial is unblinded.
So... that time is what longs and bears are anticipating. We think the SAP has been, or is about to be submitted to the RAs. How long they will take is anyone's guess. Could they be anticipating this SAP because they've been working closely with the company as this immunotherapy trial in GBM (a disease for which there has been little if any progress in treatment for, like, ever?) draws to a close, and so an approval is as easy as 1, 2, 3, and it's done in a matter of days or weeks? Or could this be drawn out into a few months? Whatever the case, we know that the company has indicated that it is "pedal to the metal" time to get this to a hard data lock. We also know that the CEO, Linda Powers (LP) thinks ASCO in June is the best place in the world to announce anything, followed by SNO and AACR. So... my guess is they are trying to get everything done in time for ASCO, but they are at the mercy of Murphy's Law and life, so we as longs (and probably the company) don't know if the unblind will occur in time or not. Regardless, an unblind draws nigh, exactly when, no one knows.
With an unblind, we can see first, how the treatment arm compared to the control arm, despite the fact that both groups were, for the most part, on treatment. But one must bear in mind that the control arm did not cross over until after they'd progressed, so they will be at a disadvantage, unless you listen to the bears who likely think otherwise. Especially ex, who thinks the control patients are doing great (lol). There needs to be a separation between the two arms as that is what will determine whether the trial's statistical significance can be determined. The SAP should also delineate what the various pathways forward "anticipating" (not knowing) what is ultimately found when the data is unblinded. Different RAs may be more amenable to certain pathways versus other RAs.
Finally, Novocure, with its FDA approved Optune helmet to treat GBM by wearing the device 22 hours a day (also a competitor), and with questionable results that DCVax-L with it's blinded data (combination of treatment and control) is already on par with, currently has a market cap of 4.23 billion. Of course, with a DCVax-L approval, Optune will not have that type of market cap, but analysts at most funds will quickly figure out that NWBO should have a market cap of at least that. And with every possible NWBO warrant on the books exercised, that would result in a share price of over $4.00.
Whew. And so, hopefully that narrative has helped answer your question. :)
AI
