NorthWest Biotherapeutics Inc (NWBO)

[SmithOnStocks]

I believe that the survival tail of DCVax-L. will be more critical to regulatory approval than proscribed endpoints of mOS and mPFS. I discuss this at length in my recent report. See this link. https://smithonstocks.com/2198-2/?co=noatrthwest-biotherapeutics

This trial started in 2007 and median enrollment occurred in May 2014. Historical results gleaned from other controlled trials indicate that for glioblastoma patients given SOC, mOS is about 16.5 months (50% have died), 70% die at two years and 85% die by year three, 92% by year four and 95% by year five. We are awaiting the publication of a manuscript on blinded data from the ongoing phase 3 trial. The lead investigators in the trial, Dr. Linda Liau and Dr. Keyoumers Ashkan have both stated publicly that patients in this trial are living longer than would be expected. See my report https://smithonstocks.com/northwest-biotherapeutics-two-lead-investigators-on-dcvax-l-phase-3-trial-believe-that-it-could-be-a-major-therapeutic-advance-in-treating-glioblastoma-multiforme/?co=northwest-biotherapeutics


Given the unusually long time the trial has been underway, we should be able to compare results for the blinded group against historical SOC results at one, two, three, four and five years. The last patient enrolled in the trial over two years ago so that the chance of that last enrollee being alive at two years if treated with SOC would be 30%. For all other patients, the chance of being alive at this point in time would be much (much) less assuming they were on SOC.

I have estimated the regulatory and medical impact for possible outcomes for mOS in this trial as compared to historical mOS. Based on looking at results seen in other controlled clinical trials in glioblastoma, I estimate that mOS for SOC is about 16.5 months. Because about 90% of the patients received DCVax-L, I am assuming that even though the results are blinded, they are a strong harbinger of results for DCVax-L when the trial is ultimately unblinded.

An improvement of 2.5 months or more in mOS for the entire patient population (331 patients; about 90% of whom received DCVax-L)) versus historical SOC (19.0 months versus 16.5 months for SOC) would be quite positive. If these results were later duplicated upon unblinding of the trial, it would very likely result in regulatory approval. The chemotherapy drug temozolomide (last drug approved for glioblastoma) was approved in 2005 on the basis of improving mOS over SOC by 2.5 months.

Key opinion leaders consider a 4.0 month improvement in mOS for a drug treating aggressive cancers like glioblastoma to be a major medical advance
An 8.0 month improvement for DCVax-L would be a home run.
Even in the first scenario of a 2.5 month improvement in mOS, I would expect widespread adoption by the medical community assuming that this led to FDA approval.