NorthWest Biotherapeutics Inc (NWBO)

[The Danish Dude]

Edited: Keep on BS'ing to your hearts delight. You've been refuted and debunked on these matters so many times during these years and it is known, that you have been a member of the hardcore short-n-distort group on InvestorVillage for years and you also have tried to manipulate with the same distortions of facts on Seeking Alpha and their many hit pieces written under pseudonyms.

A short fact checking of the recurring claims about DCVax-L’s Phase 3 design, PFS, crossover, and “post-hoc” analyses - anchored to the trial’s peer-reviewed paper and NWBO’s SEC filings.

What the record actually shows

1) PFS became unusable for immunotherapy reasons the field already knows.
DCVax-L’s investigators reported - in the JAMA Oncology paper - that *pseudo-progression* (treatment-related inflammation that looks like growth on MRI) made the PFS endpoint scientifically unreliable, so PFS could not serve as a valid efficacy readout

2) The analysis plan (SAP) was set before unblinding; it wasn’t a “save.”
The JAMA paper states the statistical analysis plan was finalized *before* unblinding, with analyses prespecified. That plan centered efficacy on Overall Survival (OS) and described how to use external controls because crossover would erase a clean internal OS comparison

3) Crossover was built into the protocol and blinded; it contaminates any simple “placebo vs vaccine” OS look.
The company’s 10-K explains the Phase 3 allowed placebo-arm patients to receive DCVax-L at recurrence while blinding was maintained. That design is ethical in GBM, but it destroys an unbiased internal OS comparator—hence the SAP’s external-control approach.

4) External controls were not an after-the-fact trick; they were SAP-defined and methodologically standard.
The JAMA paper details the use of contemporaneous external control cohorts and matching/adjustment (e.g., MAIC) to balance key prognostic factors when crossover makes within-trial OS uninterpretable.

5) The OS results—oncology’s gold-standard endpoint—were positive and statistically robust.
For newly diagnosed GBM: median OS 19.3 months (DCVax-L) vs 16.5 months (external controls); HR 0.80; *P* = .002. For recurrent GBM: median OS 13.2 vs 7.8 months; HR 0.58; *P* < .001. These are the main efficacy findings of the peer-reviewed publication.

6) “Placebo-only OS” after crossover is not a fair test and wasn’t the plan.
Because most placebo patients later received DCVax-L under blinded crossover, any OS calculated from the original randomization arms is biased. NWBO’s filings repeatedly warn that OS was confounded by crossover and that the SAP therefore uses external controls rather than within-study controls.

7) Regulators have already accepted the design logic in at least one concrete way.
NWBO’s 2023 10-K states the UK regulator (MHRA) approved the Pediatric Investigation Plan (PIP) *including approval to use the same trial design with external controls as in the Phase 3*. That is direct evidence the approach itself is not viewed as improper

8) “PFS was numerically longer on placebo, so the trial was negative” is a bad inference.
The JAMA paper explains *why* PFS is confounded in GBM immunotherapy: pseudo-progression shortens measured PFS in the active arm and does not affect placebo in the same way. Drawing conclusions from PFS in this setting misreads the biology and the prespecified plan.

Bottom line for diligent retail investors

* The PFS endpoint *was* rendered unreliable by pseudo-progression; that is documented in the publication.
* The OS-focused, external-control analysis was **prespecified before unblinding** and delivered statistically significant efficacy in both newly diagnosed and recurrent GBM.
* UK regulators have already signed off on a PIP that **uses the same external-control design**—a tangible signal that the approach is acceptable for review.

Claims that the trial was “saved” by post-hoc cherry-picking invert the documented sequence. The peer-reviewed methods and the company’s SEC disclosures show the opposite: the plan anticipated the immunotherapy realities (pseudo-progression and crossover), locked the analysis before unblinding, and then met the OS endpoint under that plan.

I would recommend you to further read this, because this completely reassure retailers about how the clinical trial was executed and not least, how MHRA has validated its use beyond any doubt. Though I share no illusions that you will. Rather I assume you will continue to disregard facts, and instead feed fud. As is your whole "reason to be".

Excerpt:

Methodological Consistency: DCVax-L Trial Design

NWBO’s DCVax-L Phase III trial used a rigorously constructed external control arm drawn from contemporaneous randomized glioblastoma trials. The control patients were selected using pre-specified criteria, including:

* Age
* Karnofsky Performance Status (KPS)
* MGMT methylation status
* Extent of surgical resection
* Steroid use

All selection and matching were conducted by independent statisticians in a fully blinded manner, with no involvement from the sponsor. These methods are documented in the JAMA Oncology publication (Liau et al., 2023).

This approach is directly mirrored in the MHRA guideline:

“The matching algorithm, baseline characteristics, statistical methods and sensitivity analyses should be pre-specified in the study protocol or statistical analysis plan.” (Section 4.3, Lines 122–123)

Regulatory Status of the Guidance
The MHRA acknowledges the legal and interpretive status of the document:
“This guideline outlines the MHRA’s current thinking and does not create or confer any rights for or on any person and does not operate to bind the MHRA or the public.”
(p. 5)

This language confirms that the draft reflects the regulator’s live operational stance and informs ongoing scientific advice, especially for innovative trial designs in oncology.

The Pediatric Investigation Plan (PIP)
Critically, this guidance builds upon existing regulatory precedent. In June 2022—well before the 2025 guideline—the MHRA approved NWBO’s Pediatric Investigation Plan (PIP) for DCVax-L. The company confirmed:

“The PIP calls for the same trial design as the Phase III trial of DCVax-L in adult GBM. This trial design includes a standard of care control arm based on contemporaneous, matched external controls, rather than a placebo control.” (NWBO Press Release, 9 June 2022)


Because PIP approval is a legal prerequisite for any adult marketing authorisation application in the UK, this decision represents a binding confirmation that the MHRA accepted the use of external controls in both pediatric and adult settings.
When viewed together—the PIP approval, the design of the DCVax-L trial as published in JAMA Oncology, and the wording of the 2025 MHRA guideline—there is no ambiguity. The MHRA has:

* Already evaluated and approved the DCVax-L external control methodology in a formal regulatory context.
* Subsequently issued a guideline that explicitly supports the same design principles.
* Rejected any narrow or exclusionary view of what constitutes valid real-world data, stating:

“There is no general scenario where the use of RWD external controls is explicitly ruled out.” (Section 1.3, Line 39)

Thus, any claim that the MHRA’s 2025 guidance “has nothing to do with” the DCVax-L trial is not only inaccurate—it is directly refuted by the regulator’s own words and actions. Far from being excluded, the DCVax-L trial exemplifies the kind of ethical, scientifically grounded external control design that the MHRA is now codifying into forward-facing guidance.

While the technical and policy details are central, so too is the institutional voice behind them. According to the APPGBT’s appendix, the NWBO representative who gave evidence during the inquiry was CEO Linda Powers. Her participation in the formal record reinforces that the DCVax-L methodology was not only recognized but advocated at the highest level of company leadership, adding further authority to the regulatory and ethical arguments that followed.

Thank you Seekingfostercare for your rebuttal here:

Conclusion
This dendritic vaccine trial has several limitations. These limitations include changing the primary endpoint (OS instead of PFS), creating a new study population (recurrent glioblastoma), conducting unplanned analyses, using external controls in a design originally intended to be randomized, all changes occurring years after the trial finished enrollment. The selected external controls likely included patients with less favorable outcomes, which opposes the “fit-for-purpose” criteria usually applied in selecting external controls. Therefore, the purported survival benefit from the vaccine is unreliable. The accumulation of limitations, along with multiple changes made over nearly two decades; further hamper the reliability of the reported results. Without data sharing, those concerns cannot be alleviated. Glioblastoma is the most common primary brain tumor, and there is no valid reason to stray from the gold standard of a randomized-controlled trial with overall survival as the primary endpoint in order to change clinical practice. Dendritic cell vaccination is a very promising approach for GBM, the neuro-oncology medical community can only regret that due to the described DCVax-L trial weaknesses, we cannot draw any conclusions on potential efficacy.
https://www.sciencedirect.com/science/article/pii/S0035378723009190?via%3Dihu

PS....
"The Pediatric Investigation Plan (PIP)
Critically, this guidance builds upon existing regulatory precedent. In June 2022—well before the 2025 guideline—the MHRA approved NWBO’s Pediatric Investigation Plan (PIP) for DCVax-L."

That PIP trial design was rejected by field clinicians and is apparently being re written by NWBO,... No confirmation of the new trial , to date.

1) “They changed the primary endpoint to OS and did unplanned analyses.”

The trial’s Statistical Analysis Plan (SAP) was finalized before unblinding because pseudo-progression (PsP) made MRI-based PFS scientifically unreliable for immunotherapy. The SAP prespecified focusing on Overall Survival (OS) and the use of external controls once crossover made a within-trial OS comparison infeasible.

2) “They created a new study population (recurrent GBM).”

Recurrent GBM OS was prespecified as the secondary endpoint (measured from first recurrence). That is not a post-hoc population; it’s in the methods.

3) “External controls in a trial that was supposed to be randomized.”

The study was randomized and blinded, but crossover (placebo patients receiving DCVax-L at recurrence) ethically contaminated any simple internal OS comparison. The SAP therefore prespecified external controls—an approach the paper states is increasingly recognized when RCTs are infeasible in this setting.

4) “They did this years after enrollment ended—so it’s untrustworthy.”

The paper states the SAP and methods were set before unblinding, and data were collected by independent CROs and analyzed by independent statisticians (Quantics). The article includes a data-sharing statement (Supplement 3).

5) “External controls were cherry-picked and not fit-for-purpose.”

The JAMA article describes contemporaneous external controls from multiple randomized trials and explains why MAIC (matching-adjusted indirect comparison) was used to balance patient characteristics when individual-patient data are not available—explicitly addressing fit-for-purpose.

6) “The survival benefit is unreliable; the trial was negative.”

The peer-reviewed conclusion reports clinically meaningful and statistically significant OS benefit in both newly diagnosed and recurrent GBM, with notable long-term survival “tails.”

7) “Regulators won’t accept this; stick to RCT OS only.”

NWBO’s 10-K reports MHRA approved the Pediatric Investigation Plan (PIP) using the same external-control trial design—a concrete sign the design is acceptable for review. (Risk language about “may not allow” is standard boilerplate.)

Fact 1 — The PIP was approved by the regulator, not “field clinicians.”

NWBO disclosed that the UK MHRA approved the Pediatric Investigation Plan (PIP) in 2022, and that the approval included permission to use the same trial design with external controls as in the Phase 3. That’s a direct regulatory sign-off on the design principle, not a rejection.

“One of the pre-requisites — obtaining regulatory approval of a Pediatric Investigation Plan (PIP) — was completed during 2022 on an accelerated basis, including regulatory approval to use the same trial design with external controls as was used in the Company’s Phase 3 trial.”

Fact 2 — MHRA approval of the PIP is contemporaneously recorded.

An NWBO press release (noted in a law-review analysis) also records the PIP approval in 2022.

Fact 3 — The program advanced to MAA submission, consistent with a live, accepted plan.

NWBO filed its Marketing Authorization Application (MAA) with the MHRA on Dec 20, 2023, which is not what you do if your PIP/design has been “rejected” or scrapped.

Bottom line:

The PIP was approved (with the same external-control design) by the MHRA.

There is no company filing indicating that the design was “rejected” by clinicians or that the PIP is being rewritten.

The MAA submission in Dec 2023 is consistent with a continuing, regulator-accepted path, not a reset.

The “rejected PIP” narrative is contradicted by NWBO’s own SEC-filed disclosure and contemporaneous records of MHRA approval.

Stop posting lies

Please do! Only one of us created a fud account a month ago.