Replies to post #770404 on NorthWest Biotherapeutics Inc (NWBO)

[learningcurve2020]

The FDA had already approved it.

[Investor082]

But you were BSing about an approval end of May. What happened to that?

[exwannabe]

Lykiri, objective response (tumor shrinkage) has long been considered suitable for approval based on single arm trials while OS has not.

There is a sound reason for that. So this example means nothing.

[dennisdave]

The 22 May 2025 article https://www.raps.org/news-and-articles/news-articles/2025/5/euro-roundup-mhra-seeks-feedback-on-using-external is 100% about the DCVAXL application. Unless you know about another application in the MHRA pipeline that:
Uses a non-randomized external control arm.
Lacks patient-level comparator data, and is based on a statistical comparison to the summary RWE, which the article is talking about

The MHRA asks for comments until June 30 so yeah, the MHRA is waiting until the comments are all in and thus until June 30 at least.

On 31 December 2024, they approved tarlatamab (Imdylltra) for adult patients with extensive-stage small cell lung cancer (SCLC) after at least two prior lines of therapy, based on a Phase 2, open-label, dose-ranging study (DeLLphi-301) with no control arm. The approval was supported by a 40% objective response rate in the 10 mg group. No formal RWD framework or consultation preceded that decision.

Its clear you have very little understanding of what the DCVAXL application is based on when you are comparing it to the tarlatamab (Imdylltra) for adult patients application.

Tarlatamab (Imdelltra) – Approved by MHRA (Dec 2024)
Trial Design: Phase 2, open-label, single-arm, dose-ranging trial (DeLLphi-301).
No control arm — no RCT, no ECA.
Decision was based on: ~40% objective response rate (ORR) in the 10 mg cohort.
Strong duration of response (DoR) and tumor shrinkage metrics.
No ECA or RWD comparisons were required or presented.
The endpoint (ORR) is a direct, measurable outcome, reducing the need for comparisons.
There was no regulatory consultation launched before or after to validate single-arm designs.
Why approval was smooth: In oncology, single-arm trials are acceptable when the effect size is large and the disease is advanced with no standard options.
ORR is a hard endpoint — it doesn't need a comparator to be credible.
Safety was manageable and response durable.

DCVAXL Trial Design:
Phase 3, randomized, double-blind, with a crossover design that ultimately blurred the control group.
Comparative analysis relied on a synthetic External Control Arm (ECA) using summary-level Real-World Evidence (RWE) from other GBM trials.
No access to individual patient-level comparator data (IPD).
Major challenge: The primary endpoint (OS) is not a direct measure of tumor response.
To prove OS superiority, a valid control group is critical — but NWBO lacked a clean internal control and had no access to IPD for the external comparisons.
Therefore, the magnitude of effect must be both large and credibly unbiased — a harder standard to meet than ORR in relapsed SCLC.

So yeah the MHRA asking for comments on this new framework NWBO is setting is highly justified.
Either you are deliberately spreading false pumping information OR you have very little understanding of how biotech works.