Replies to post #79476 on NorthWest Biotherapeutics Inc (NWBO)

[JeansOnFire]

Information overload. No just kidding. You are an amazing gift for this mb. And we are very lucky to have someone like you spreading wisdom and info. Thanks.

[doingmybest]

RK, thx so much for the comprehensive re-count of the trial. I do not follow where you state there were "probably at least 190 patients before 2015". But, I follow the majority of the rest. The additional arms can cloud the critical path of the 348 patients in the base trial. You think that the company reached the 348 full enrollment or close to it around or shortly after the screening halt but decided to remain silent about enrollment due to regulatory communications I presume. The main assumption one has to make is what will the SOC PFS look like. Take a look at this overly simple set of numbers, using your enrollment numbers:

Active Placebo Total
Up to EOY 2013: 113 56 169
2014 48 24 72
2015 72 35 107
Totals 161 115 348

Now assume a median of active PFS of 24 mos and a placebo PFS of 12 mos and start with the assumption that 248 gets reached in Dec, allowing virtually a full 12 mos of 2016:

Evented 95 56 169
36 24 48
18 20 20
Totals 149 100 249

The most important assumption is the PFS for the placebo population. If the median of the active population is double the median of the placebo population then the target completion date is when 1/2 of the active population has evented, since the target number of events is approx. 2/3 of the entire trial population. But, if the active population median is less than double the placebo timing or greater than double this relationship does not hold. So, we can only provide an educated best guess for the placebo eventing and go from there. The higher the placebo eventing median the lower the active eventing median and vice versa. But, if we start with a 12 mos blended mgmt. methylation promoter population since that seems reasonable, things look good. If you assume a 15 mos placebo median it starts to tighten up considerably. But, isn't that quite high for a blended placebo population? Am I wrong here?

Again, I want to extend a deep appreciation for all your work here, wow.

[sentiment_stocks]

Thank you... very helpful post. Your work is most appreciated. :)

[sentiment_stocks]

I have a couple of points to consider regarding your enrollment numbers… although I’m not sure it really matters at this point.

I believe the trial enrollment numbers were more like 22 BEFORE the restart in Q3 2011 - not 11 as you suggest. And with that restart, I think enrollment wouldn’t have begun until 3 months AFTER the screening process. I’ll give more information on that below.

Q3 2008: 11 patients
Q3 2011: 4 patients (15)
Q4 2011: 8 patients (23)
Q1 2012: 12 patients (35)
Q2 2012: 14 patients (49) - RK

First: there were actually 11 patients in the clinical trial (and therefore not the info arm) as of November 19, 2008

From the 10Q - ending September 30, 2008 / filed and signed November 19, 2008

We plan to rely on our current DCVax®-Brain Phase II clinical trial as a single study in support of regulatory approval. However, to date, only ELEVEN patients have enrolled in the clinical trial, which is designed to include 240 patients. - page 42
https://www.sec.gov/Archives/edgar/data/1072379/000136231008007500/c77426e10vq.htm

So as you can see, these 11 patients were all enrolled BEFORE 2009, in fact as of November 19, 2008.
And the clinical trials.gov site shows in the history that the trial is still “Recruiting” all the way until June 9, 2009, when it goes to “Active, NOT RECRUITING”.

And then in their January 24 2011, their PR states they are treating a total of 33 patients (albeit, the words “enrolled” were confusing as a portion of these patients really were “enrolled” in the info arm:

To date, this trial has been conducted at 13 clinical sites across the U.S., with 33 patients already having been enrolled. These patients have continued to be treated with the DCVax® regimen and follow-up during the last two years. The only aspect of the trial that stopped for a period of time was the enrollment of additional new patients beyond the 33 patients who were already enrolled and receiving ongoing treatment. The Company is now resuming the process of accepting additional new patients to complete the trial.
www.nwbio.com/northwest-biotherapeutics-resuming-enrollment-in-promising-240-patient-clinical-trial-of-dcvax-for-brain-cancer-2/

And these patients had to have come from BEFORE June 24, 2011, as their trial is listed as not recruiting until that date on the history of changes on the Clinical trials.gov site.

And finally, buried in their S-1 filed December 22, 2011, they actually state the breakdown…

The Company has already enrolled and treated 34 patients in this Phase II trial, including 22 patients in the trial arms and 12 patients in an information arm, and the Company has similar numbers of additional patients in various stages of the screening and enrollment process.    The Company plans to add a substantial number of additional clinical trial sites over the coming months. - page 27
https://www.sec.gov/Archives/edgar/data/1072379/000114420411071421/v242197_s1.htm
(thank you Avii from i-v post #4097. It took FOREVER to find the link to this as I kept looking in the 10ks and 10Qs.)

My guess is that the difference from 34 and 33 is that one of the 12 patients in the Info Arm was dropped... maybe not enough vaccine? - bringing the number to 11.

And the 2011 10K filed on April 9, 2012 also states that they…
The Company obtained a new FDA clearance and re-approvals by all the clinical sites, and commenced the new Phase II trial in early 2009. - page 10

https://www.sec.gov/Archives/edgar/data/1072379/000114420412021574/v306928_10k.htm

Given this clearance, it seems they enrolled 11 additional patients over the next 6 months in addition to the 11 enrolled by November 2008.

Then finally, on June 24, 2011 - the clinical trials history changes to list "Recruiting" again. However, any patients recruited at this time would still have to go through the 3 months of screening for psPD and rapid progression. So they technically wouldn't “enroll” into the actual trial until around the end of September, at the earliest, and maybe more like in October 2011 - or Q4.

So maybe your initial enrollment numbers leading up to August 2012 would adjust more to something like this?

2008: 11 patients
2009: 11 patients (22) - comprise the Vanguard cohort)
2011 Q4: 7 patients (29) - begin the Restart cohort)
2012 Q1: 8 patients (37)
2012 Q2: 8 patients (45)
2012 Q3 - partial: 4 patients (49) by August 2012 as German Protocol indicates

And then adjust accordingly if you want to hit around 187 to 190 by 2013 Q4 or 2014 Q1?