Replies to post #209801 on NorthWest Biotherapeutics Inc (NWBO)

[biosectinvestor]

I missed that point in the previous post. I agree. I have always asserted that I strongly suspect that the halt was due to efficacy and the morality / immortality of taking more placebo patients under their protocol given what they were seeing. The Germans are particularly anxious about such experimentation on people, given their history... and any such halt by ANY international regulator gets mirrored by the FDA immediately.

[exwannabe]

The company has stated that no efficacy peek occurred at that time.

You are mistaken We are talking about 2015 when LP had stated an efficacy IA would be performed and subsequently they have never mentioned it.

You are confusion this with 2014 when they said and efficacy IA would be performed then was slow to come clean that the trial had been enlarged and would take longer.

Also, a futility analysis (if done) would be part of the efficacy IA, and uses unblinded data.


Also, this "preserve the integrity of the trial" excuse is now off the table. The trial is over other than OS phone follow-up. There is no place left for bias to be introduced.

[sentiment_stocks]

Also, Early Access Programs are FDA approved and reserved for drug candidates where FDA/EMEA believe efficacy is highly likely or already proven. In my experience, these are only initiated prior to approval, but after NDA filing. Why would FDA allow at least 110 EAP patients if they questioned efficacy?...hmmm.

And to boot, the EAP trial was put in place in May 2014 at the SAME TIME that the psPD arm stopped their enrollment at 32 patients, rather than going to 48, or increasing enrollment as was done with the main arm.

[iwasadiver]

MI Dendream;

I wasn't really referring to the halt with what I was saying. I was stating that there appears to me, inferring from all the cumulative issues and the types of attacks by shorts and others, the data that's public, and all the correspondence from the company that's public, that something weird may have been seen to be going on with the PFS at some point, whatever that might have been.

Your explanation makes sense completely, especially regarding the randomization. Perhaps the pseudo progression issue was only a headache in some other way, other than it's impact on PFS.

Your final thought, that PFS was already positive, could be precisely that; a continuation of the trial as a confirmatory trial perhaps. That makes more sense than anything to me.

[abeta]

MID -

-- statement
-- and question

thanks for your 2017 thoughts -

1) data was submitted to a regulator (assumed to be FDA) and ongoing conversations occurred
2) patients already enrolled in the trial continued treatment
3) patients in screening were allowed to enroll in the trial - LP indicated that she planned to complete the trial through OS
4) Early Access Program(s) which require regulatory approval and treated in most ways as a single arm clinical trial without enrollment limits were initiated and implemented.
5) Approximately 30ish patient entered the trial after halt and over 100 received active treatment under EAP.
6) construction of new manufacturing capacity in England continued
7) manufacturing partnership in Europe were renewed
8) additional sites were activated in the trial because the process to onboard a site for commercial purposes is similar to the research activation process (thus speeding the time to commercializations in those centers)
8) the company announced that it agreed to stop enrollment at 331 instead of the previously defined 348 and the hold from FDA was lifted in February.
9) the company announced that the primary event trigger of 248 was reached by February 2017 and indicated that it would take several months to reach the OS trigger and a few months after wards to complete data lock.
10) the company announced in June that they were approximately 1 month away from reaching OS trigger of 231 and that ONLY 7 SAEs have been reported.
11) 108 patients of 331 remained alive and 12 are LTFU as of March 2017.
12) the final 30-32 patients enrolled in the trial were put on treatment only. There is some dispute whether these patients will be analyzed with the entire Intent-to-Treat cohort, but they do appear in the unblinded publication. I believe strongly IIT is just that consented and intended, Thank You FDA..
13) Based on Lykiri hash mark counting mOS for the total cohort is likely to increase from 23.1mo and based on KM curves this is likely in the 1-2 mo range.
14) we know know within a patient or 2 how many remained only on SOC vs crossing over to DCVaX.
15) we know if you make it to three years, you are likely to be ‘cured’ and there is a big cohort approaching or past 3 years now.

That's the facts, Jack! Based on points 1-5 and 10 it can be concluded that the hold was not due to safety or manufacturing concerns as has been widely speculated here by naysayers.

For those not familiar with clinical operations within industry, it should be understood that initial data analysis typically precedes final data lock. Final data lock is a process of verifying clinical reports against source data and quality checking data entry at sites. Preliminary results can vary somewhat but generally the first read is very close to the final set. Thus, I believe the result at least for PFS and likely OS is and has been in hand. I also believe that if it were negative it must be immediately shared publically. Clearly raising funds with knowledge of negative results would be criminal.

My base theory has always been that the hold in August 2015 was initiated due to a futility review and DSM recommendation after viewing blinded data, but that extreme efficacy on PFS was presumed. EAP approval supports this theory as does several other clues along the way.

===========================================================

Question - Linda wrote in November

Ms. Powers continued: “We believe it is now appropriate for the Company to move forward with the several stages of work that are needed to reach completion of this trial program, despite the fact that there are good arguments for allowing the data to mature even further.

The upcoming stages include finalizing the Statistical Analysis Plan, conducting the final data collection, data validation and data lock, and then unblinding and analyzing the data.

Does this follow the same patterns you have seen before?

Thanks

regards

[marzan]

Excellent post. Thanks Dendream!

[sukus]

Excellent!