Replies to post #374224 on NorthWest Biotherapeutics Inc (NWBO)

[hope4patients]

Excellent post.

[Dr Bala]

Awesome post, Senti. Thanks.

[AVII77]

Unfortunately the paper you reference in your post, “Rapid Early Tumor Progression is Prognostic in Glioblastoma Patients”, is behind a pay wall so isn’t fully available for most of us to review.

https://pubmed.ncbi.nlm.nih.gov/30973372/

Sorry you don't have access Senti.

One should note, however, that the snapshot in the link you provided indicated that it involved a total of 87 patients, 52% of which were (rapid early progressors) REP. That means the sample that you cite for comparison of the mOS of the unmethylated and methylated (19.6 and 34.7) is for a fairly small sampling of only 42 patients. And because of the pay wall, the link you provided prevents us from seeing what was the entry criteria for this group.

Your assessment (small sample size) is correct.

As for entry criteria:

A total of 107 consecutive patients were reviewed of which 87 patients met entry criteria. Demographic variables, tumor characteristics, and outcomes are summarized in Table 1. Of the 87 patients, 45 patients (52%) met the criteria for REP.

They looked at consecutive treated patients. No selection other than "Patients were included in the final analysis if an MRI was available in the immediate postoperative period (24 to 48 h) and between the postoperative MRI and the initiation of radiation therapy."

So while the consistence between the medians of these 42 methylated and unmethylated GBM patients is similar to the blended medians of the DCVax-L trial for methylated and unmethylated, it’s also a small sample without any other comparable criteria to show other than the meth status and that these patients had GBM.

Additionally, while most of us agree that medians are helpful as a comparative measure, you know full well that medians are not what the DCVax-L trial will be measuring, but rather the entire measure of the treatment arm’s overall survival, and of course, as it compares to the entire measure of overall survival of control arms in other contemporaneous, AND COMPARABLE trials.

I see what you did their capitalizing "AND COMPARABLE", LOL. We disagree.

But I do agree with your comment about medians (Indeed, I "know full well"). Their Fig 1 also included the KM curves (out to 75 months).

Which reminds me, ever figure out why Liau stopped their KM curves at 36 months? I mean, come on, the "tail" is so important. Why not show it?

Anyway. That hidden data is probably a sore spot for longs.

And while you may find this type of ECT comparison objectionable, it appears that the SAB, the steering committee, the multitudes of primary investigators, Northwest management are all prepared to utilize them to file BLAs with the RAs, despite your objection.

Did I miss something Senti? Has management ever said anything about intending to file a BLA?

I rather doubt they would comment on that. If they did, they would have to disclose what the FDA told them about their endpoint change (the utility, or lack thereof, to use it to support a claim of substantial evidence of efficacy). I would be amazed if you read anything about them planning to file a BLA in any of the recent filings.

I did a quick search and see they say:" The statistical analysis plan uses external control patients rather than within-study controls. There can be no assurance that regulatory authorities will allow a product approval to be based upon this approach."

I would say that is an understatement if ever there was one. I would think "no assurance" should read "no chance in hell".

So I’m sorry that while you may find a 25% chance of living five years or longer a meaningless metric, I am certain there are many neurosurgeons, neuro-oncologists, and GBM patients who will not agree with you.

First: What's the provenance of the 25% at 5 year claim? Have you seen a KM curve I haven't? Liau's paper shows about 25% at 3 years. Where did this 5 year thing come from?
Second: The claim is meaningless unless it is compared to a valid control. Yes, some GBM patients will live 5 years.

The diagnosis of GBM offers an extremely and consistently poor prognosis (as you know), and there is a myriad of very qualified KOLs that seem to think the regulatory agencies are willing to consider this ECT comparison. And that is ultimately what counts, and not what simply doesn’t comport for you in particular.

Extremely poor prognosis yes, consistently poor, no. Some do better than others. You know this Senti. You just fail to appreciate that a RCT is required to understand if a treatment is having a beneficial effect on survival.

That's my 15th post for the day. If I have anything else to say look at the other board. I truly hope you and your family are well.

[MI Dendream]

Love it, nice work Senti!

[sukus]

Beautiful!

[eagle8]

Awesome !

GLTU