NorthWest Biotherapeutics Inc (NWBO)

[Dan88]

I guess you may be somewhat confused on several issues:

The SAP and the endpoints the analyses will use when data is unblinded will be the revised reordered SAP and endpoints therewithin, ie, the primary endpoint is

"The primary objective of this study is to compare overall survival (OS) between patients randomized to DCVax-L and control patients from comparable, contemporaneous trials who received standard of care therapy only, in patients with newly diagnosed glioblastoma. This endpoint will be assessed using 3 different analyses"

and the first secondary endpoint is

"The first secondary objective is to compare overall survival (OS) between patients randomized to placebo who received DCVax-L treatment following disease recurrence and control patients from
comparable, contemporaneous clinical trials, in patients with recurrent GBM."

Source: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-001977-13/GB

As we all know, part of the reason for revising SAP (endpoints are part of it) is pseudo-progression wreaking havoc on "original" primary PFS endpoint and cross-over confoundment on "original" secondary endpoint OS."

Nonetheless, sponsors of trials may revise respective SAPs while they remain blinded according to FDA guideline, and it's exactly that NWBio revised its SAP while remained blinded. NWBio would be (has been) for the first time using this SAP to analyze unblinded data.

After all, since well more than five years have passed after the last patient in the trial was enrolled and treated, any data/analyses on PFS will be truly secondary, which may be used as an evidence support. The focus is now and should be now squarely on OS, in particular long-term survival.

It should be stressed NWBio revising SAP and endpoints are conducted to have more accurate and up-to-date metrics used to measure efficacy of the trial data, not to make up for "a failed trial" so it is not only necessary but essential.

One other reason for revising SAP is obviously as of today it is understood any immuno-therapeutic trials must be conducted longer enough to fully capture the effectiveness of the underlying immuno-therapeutic agents/vaccines due to normally delayed effects. For this reason, long-term OS is most important relative to the median OS, or the now obsolete surrogate endpoints such as PFS. Not only has NWBio exactly done that but it has acquired unprecedent rich and extensive data for all patients in the trial.

With Dr. Liau's presentation slides, particular those comparable, contemporaneous prior trial curves as well as the blinded data of Phase 3 DCVax-L trial as of 2017 (published in 2018) and its subsequent update data in 2018, plus the information arm data presented, it should be no difficult to conclude both the primary endpoint and the first secondary endpoint will be significant when analyses of unblinded data are announced in the near future.

GL