NorthWest Biotherapeutics Inc (NWBO)

[hyperopia]

ATLnsider, I admire and respect those (like you) who share their research and theories and are willing to go out on a limb. Admittedly, I haven’t read all of your posts or the board lately, but I’ve read a few posts like this one, presenting a case for the approval of ICLC along with DCVax. From what I’ve read, you make a pretty good case. I don’t have time to get into a back and forth, so I’ll just state my thoughts, and you can have the last word if you wish.

Normally, when a company develops a drug, they establish its safety and efficacy in clinical trials, then apply for and potentially receive approval based on data from those trials, and then continue to make manufacturing improvements, and begin various trials to expand its use. I think the dilemma of whether to include poly ICLC in the marketing application arises because it has taken Northwest Bio so damn long to complete the phase III trial, present the results, and apply for approval. In the extraordinary time it has taken, an incredible amount of knowledge outside of the trial has been established about DCVax itself, and its efficacy with different combinations, by Dr. Bosch, the Neuro-Oncology teams at UCLA and Kings college, et al, that it almost makes the outstanding clinical trial results seem obsolete. I agree with your theory about current and future trials including poly ICLC in the treatment regimen with DCVax, and I understand the rationale for the approval of ICLC along with DCVax. However, I still don’t believe that Northwest Bio will include poly ICLC in its initial application for marketing approval because I believe the data is incomplete.

As Linda Powers said a few years ago, it’s important to establish DCVax-L as a safe and efficacious therapy to discover what it can achieve on its own, as a baseline. DCVax may be combined with many different agents that have different mechanisms of action that may be best for a particular or different types of cancers, and it wouldn’t be prudent to limit its formulation, or use, in any way initially.

I’m pretty sure that poly ICLC was not used in any part of the manufacturing process to make DCVax-L. Every (redacted) manufacturing protocol that I’ve read for DCVax-L, (including the supplement to the JAMA article) only lists granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) as the cytokines used in the cell culture media, which is the most common, reliable, and well established method for differentiation, maturation, and activation, when the clinical trials started.

Generally, during clinical trials, the use of other medicines or treatments that could have an effect on, or interfere with, the safety or efficacy of the drug or therapy being investigated, are excluded and prohibited. This is evidenced in the trial protocol in Supplement 1 of the JAMA journal article where it said this under the heading concomitant medications:

other treatments and medications that may affect immune function, that have known or suspected anti-tumor activity, or that could interfere with the imaging assessment of disease progression are not allowed for patients prior to crossover.
The use of other investigational agents is not permitted.
Active immunotherapy is not allowed for any patient.

I think that obtaining the company’s very first regulatory approval is so critically important, that Northwest Bio will not want to jeopardize it, or complicate it in any way and (further) delay the initial regulatory filings to include poly ICLC, since it wasn’t a part of the clinical trial. All available evidence to date about DCVax-L has shown that it’s safe and efficacious, and approvable all on its own.

Now, it seems reasonable to think that once DCVax-L is initially approved by regulators (as a monotherapy) based on the protocols that were used during the clinical trials, then Northwest Bio will attempt to expand its use to include poly ICLC for nGBM and rGBM, and will present the clinical evidence of the combination’s safety and efficacy, chemical composition, function, and manufacturing data of the components, and will include the specific regimen that includes poly ICLC. Also, if Dr. Ashkan is using poly ICLC in the treatment regimen for the compassionate use patients in the UK, there may be Real World Evidence that could potentially speed the process.