NorthWest Biotherapeutics Inc (NWBO)

[Lykiri]

That 66th event efficacy interim was never conducted. Rather, they resized the trial such that the first efficacy interim would occur at 149 events (still 60% but now 60% of the resized target of 248 PFS events).

It is that 149th event IA, mentioned by NWBO numerous times in early 2015 (yes, 2015, not 2013) where I believe a futility finding was observed. (AVII)

That is interesting, so I did my own IA 2015 that I call my BLINDED Aug 1, 2015 analysis.

All the data are from the day of surgery. I looked at the enrollment curve to figure out the date of surgery. https://askthebranko.blogspot.com/

I took the numbers of Nov.1, 2012-2013-2014 to make up the numbers of Aug.01, 2012-2013-2014. On average 3.1 months between surgery and enrollment.

Here are the numbers:

17% of 331 patients had surgery 36 months or more before the date of MY BLINDED IA Aug.01, 2015 = 56 patients.

35 % of 331 patients had surgery 24 months or more before the date of MY BLINDED IA Aug.01, 2015= 116 patients.

64% of 331 patients had surgery 1 year or more before the date of MY BLINDED IA Aug.01, 2015= 212 patients.

119 of 331 patients had surgery between Aug.01, 2014 and Aug.01, 2015.

Let's analyze the first group of 56 patients who had surgery more than 36 months before my IA Aug. 2015.(between June 2008 and Aug.01, 2012)

The 38 "unknown" patients are included in this group and we know only 6 patients lived more than 36 months. From my own DD I know that at least 5 of these 6 patients are still alive at the time of my IA Aug.01, 2015.

32 of 38 are dead (30 dead and 2 LTFU). These 2 LTFU are found dead when they did the interim analyses in 2018.

Of the remaining 18 patients (56-38), 25% have lived beyond 36 months = 4 patients. That means that 14 of 18 patients are dead at the time of MY IA.

Of the first group of 56 patients : 46 patients are dead (32 + 14) and 10 patients (6+4) lived more than 36 months.

From comment of Linda Liau (2016-2018-2019) I assume that between 75% and 80% of the patients are progression free at 36 months. In a later post I will explain why I am pretty sure that number is very accurate!

So, 75-80% of 10= 8 with no recurrence of their tumor and the remaining 2 patients are progressors (real and/or pseudo)

In conclusion: total of PFS events of a first group of 56 patients who had surgery between June 2008 and Aug.01, 2012 = 46 patients are dead and there are 2 progressors = 48 PFS events.

Let's look at the patients who had surgery between 24 and 36 months before the date of MY IA Aug.01, 2015. (between Aug.01, 2012 and Aug.01, 2013)

That is a group of 60 patients (116 - 56 = 60 patients)

At the time of my IA Aug.01, 2015 the 2-year survival rate is 41%. I learned that the 2-year survival rate increased from 41% to 46% once the UK and Germany became involved in the trial.

So, 59% of 60 patients are dead at 24 months = 35 patients.
25% of 60 patients are expected to live more than 36 months= 15 patients.

10 patients will die between 24 months and 36 months. (group of 60 - 35 dead before 24 months - 15 who will live more than 36 months = 10 patients who will die between 24 - 36 months)

The 60 patients are on average 30 months in the trial at the time of my IA Aug.01, 2015.

I assume that 5 of 10 (those who will die between 24 and 36 months) are dead at the time of my IA.

So, we have 35 patients who died before 2 years and 5 who are dead between 24 and 36 months = 40 patients.

I believe that it is reasonable to say that at least 5 of 20 patients still alive (60 - 40 who are dead) are progressors. (maybe most pseudo-progressors.)

So, in conclusion : total of PFS events (at the time of MY IA Aug. 2015) of a group of 60 patients who had surgery between Aug.01, 2012 and Aug.01, 2013 = 40 patients are dead + 5 progressors (real progressors and/or pseudo-progressors) = 45 PFS events.

Let's look at the patients who had surgery between 12 months and 24 months before MY IA Aug.01, 2015. (between Aug.01, 2013 and Aug.01, 2014)

That is a group of 96 patients. (212 - 116)

These patients are on average 18 months in the trial. I believe that it is reasonable to say that 50% of these group had recurrence at the time of my IA Aug.01, 2015. Some are pseudo-progressors and the
majority are real progressors.

In conclusion: I believe that there are 48 progressors (50% of a group of 96. Some are dead and some progressors are still alive at the time of my IA)= 48 PFS events.

I count 141 PFS events of a group of 212 patients who had surgery between June 2008 and Aug.01, 2014 = 48 of the first group + 45 of the second group + 48 of the third group.

Some members of this board believe that there are 149 PFS events in this trial at the date of MY IA Aug.01, 2015.

That means that 8 patients ( 149 - 141) of the last group of approximately 119 patients (331- 212 = 119 but 31 are not enrolled at the time of my IA Aug.01, 2015) had recurrence at the time of my IA 2015. (a few real progressors and a few pseudo-progressors)

The last group of approximately 119 patients had surgery between Aug.01, 2014 and Aug.01, 2015.

I have to exclude about 31 patients because these patients are not enrolled in the trial at the time of my IA 2015.

119- 31= 88 patients. It is reasonable to expect that 8 of these 88 patients who had surgery between Aug.01, 2014 and May 01, 2015 are progressors.(a few real progressors and a few pseudo-progressors)

In conclusion:

I don't see a big difference between my OS curve 2015 and the OS curve of the interim publication March 08, 2017 when I put all the data on a OS curve .
The most remarkable difference is the increase of the 2 year-survival rate from 41% to 46%.

My conclusion : I don't believe that a futility finding was observed in the summer of 2015!

At the time of MY IA AUG.01, 2015 around 182 patients are PROGRESSION FREE!

NOTE: why 2-year survival rate is around 41% between March 2012 and Sept.2014.

Interim publication March 08, 2017: 223 patients had surgery 30 months or more before the date of the analyses.

67 of 223 patients have lived 30 months and more. I believe that 90 of these 223 patients have lived 24 months and more.

The number of step downs between 24 months and 30 months on Sentiments Curve = 26.

I assume that 3 of these 26 are from a group of patients who had surgery between Sept.08, 2014 and March 08, 2015.
We see that 22 patients are still alive between 24 months and 30 months on Sentiments Curve. So 22 alive and I assume 3 who died between 24 months and 30 months = 25 patients who lived 24 months or more. These patients are from a group of approximate 58 patients who had surgery between Sept.2014 and March 08, 2015.

115 patients are at risk at 24 months at the time of the March 2017 analyses. (see ASCO presentation Marnix Bosch Md, June 2018)

So, 115-25 = 90 patients from the first group of 223 patients are at risk at 24 months.

We learned that from the first 38 "unknown" patients 13 of them lived 24 months or more. (the worst group)

So, let's figure out the 2-year survival rate of the next 185 patients (223-38= 185 patients)

90- 13 (group of 38) = 77 patients of a group of 185 patients lived 24 months or more.

77/185 = 2-year survival rate is 41.6% for the group of patients who had surgery between March 2012 and Sept.2014.

Sentiments Curve : https://investorshub.advfn.com/uimage/uploads/2018/10/22/gddzjCombined_charts_no_notes_revised_-lykiri.jpg