Replies to post #773414 on NorthWest Biotherapeutics Inc (NWBO)

[10baggerz]

This is the type of information sharing that makes an investment forum valuable.

As opposed to people shouting the same extremes and unfounded positions at each other. The FACT is that the MAA for DCVAX for GBM/rGBM with artisanal manufacturing ONLY is neither DEAD ON ARRIVAL nor is IT GUARANTEED WITH A CHANCE OF EXPANSION TO TUMOR AGNOSTIC + FLASKWORKS.

I own 2.5 million so I acknowledge my own bias of leaning towards approval.

While I still believe that approval is more likely than not Dr Liau’s statement below is acknowledges a POSSIBLE reason for this extended regulatory delay. What if the RFI(s) related NWBO to providing either patient level data or providing real world data based ECA?

This would certainly explain;
1)THE EXTREMELY LONG DELAY
2)THE LACK OF APPROVAL
3) THE LACK OF REJECTION
4) THE LACK OF A DISCLOSURE OF A MATERIAL ADVERSE EVENT
5) THE DISCLOSURES THAT NWBO REMAINS ACTIVELY ENGAGED WITH THE MHRA
6) THE FACT THAT NWBO IS SKIPPING EVENTS LIKE ASCO TO FOCUS ON APPROVAL
7) THE FACT THAT NWBO DOES NOT APPEAR TO BE ABLE TO START THE NICE REIMBURSEMENT EVIDENTIARY PROCESS
8) THE FACT THAT THE MHRA SAYS THE MAA IS NOT PART OF THE BACKLOG
9) NWBO NEEDING TO BE COMPLETELY SILENT AS TO THE MAA

LL:
“However, we were unable to obtain individual patient level data from the previously published comparator trials so we're not able to do individual patient matching which we are all aware is a current limitation with the use of external controls, so I'm actually hoping that our publication and the discussions around, it will spur the sponsors of these clinical trials to publicly release their individual patient data so that we as a field can further innovate and get regulatory interest in the use of external control arms in neurology and oncology trials.”

[Slave1]

Thanks for weighing in, Froggmister. I think this is a case where there’s just a bit of nuance getting lost in translation.


You’re absolutely right that NWBO did not have access to individual patient-level data from the external comparator trials. That’s confirmed directly by Dr. Liau in the Neurology Journal Podcast on March 2, 2023. She made it clear that the external control data came from previously published trials and that those datasets were only available in aggregate form.


But that’s just one side of the equation.


NWBO did have full individual patient-level data for its own DCVax-L trial participants. That is how they were able to conduct detailed analyses like delayed treatment effect modeling, survival over time by subgroup, and other landmark statistical methods that require patient-level granularity. Without IPD from their own arm, those analyses would not have been possible.


So here is the full picture:

• NWBO had individual patient-level data for the treatment group.

• They did not have IPD for the comparator RCTs, so they used a method called MAIC, Matching Adjusted Indirect Comparison.

• MAIC is a well-established approach for adjusting baseline characteristics when you only have aggregate-level data from comparators.

• Dr. Liau noted this was a limitation, but also emphasized that it was the best available option in the absence of full IPD from legacy trials.

• The MHRA accepted this framework, escalated it to the Commission on Human Medicines for expert review, and went further by expanding the early access program.

That last point really matters: if the lack of external IPD were a fatal flaw, none of those steps would have happened. MHRA clearly judged that the analysis met the bar for serious regulatory consideration.



🔍 Analogy:

It’s like saying a chef didn’t cook a meal because they didn’t grow the vegetables.In truth, the chef had full control over their main ingredients, crafted the dish carefully, and substituted responsibly when some outside ingredients weren’t available. The regulators at MHRA tasted it and invited more people to the table.

[Galzus Research]

The evidence of a benefit was sufficient to justify a more thorough review. The phase 3 trial offers little in saying DCVax does NOT work. So compassionate use is a reasonable thing to allow here.

But the phase 3 trial also has some serious issues that may not be surmountable. That can be true at the same time that they would accept the application. Look at Urogen’s FDA application and their issues leading up to approval.

Longs here would be saying that the FDA would never have accepted Urogen’s app if they had an issue with the trial design (which they very much did)

[The Danish Dude]

This PDF documents the official recognition and regulatory validation of DCVax-L’s external control methodology by UK institutions.

“The Collaboration between NWBO and the UK – Part 1”

It shows that:

The APPGBT explicitly recommended replacing placebos with external controls—using NWBO as its only oncology case study.

The MHRA’s 2025 draft guidance endorses real-world and trial-derived external controls—fully aligned with the DCVax-L model.

The Pediatric Investigation Plan (PIP), approved by MHRA in 2022, confirms the same methodology was pre-approved for pediatric use.

The report dismantles common misinformation, including the claim that individual patient-level data (IPD) was not used in the DCVax-L trial.

✅ Yes, DCVax-L used individual patient-level data (IPD).
✅ Yes, it applied statistical weighting using MAIC to match external comparator trials.
✅ Yes, this was publicly documented at ASCO 2023, in JAMA Oncology
✅ Yes, this was publicly documented in a webinar with Dr. Liau and Dr. Musella (transcript available)
✅ Yes, the MHRA formally approved this design—before the APPGBT report was published.
❌ Claims that the trial lacked IPD-based matching are verifiably false.

Below is the full report in images, if you won't read it on its own.