Replies to post #753686 on NorthWest Biotherapeutics Inc (NWBO)

[XMaster2023]

The trial design is now antiquated, the end point (OS) is antiquated and the drug DCVax-L will not be used as a mono therapy. It’s an I dotted and T crossed because it was required for approval by MHRA. Think about it. Within 3 years, the game has changed. It’s amazing.

[The Danish Dude]

Thanks for yet again adding to the entertainment HyGro. And good to see you on Seeking Alpha continue to spread your vast arsenal of nonsense.

HyGro’s argument that the PIP approval was only for the trial design and not the drug itself is a misleading attempt to downplay the significance of the approval.

Why HyGro’s Argument is Misleading:
1. PIP Approval Requires Regulatory Endorsement of the Trial Design
• The MHRA does not approve PIP plans unless the underlying product is considered viable for pediatric use and has a reasonable expectation of approval in adults.
• The fact that the PIP was approved in 2022 means that the same statistical analysis plan (SAP) and trial methodology were accepted by the MHRA.
• If the SAP was “unapprovable,” as some skeptics suggest, then why would the MHRA approve the PIP based on that very same methodology?
2. DCVax-L’s Clinical Relevance Has Evolved – Not Been Invalidated
• As XMaster2023 correctly points out, the field of neuro-oncology has progressed, and modern combination therapy designs incorporating checkpoint inhibitors (e.g., pembrolizumab) and RANO criteria are now more standard.
• However, this does not mean that DCVax-L as monotherapy is ineffective. It simply reflects the natural progression of cancer treatment paradigms—combining multiple approaches to maximize efficacy.
• DCVax-L is still the backbone of these combinations, not being discarded. This is evident in UCLA-led studies where DCVax-L is combined with PD-1 inhibitors.
3. PIP Approval is a Formal Step Toward Full Approval
• A PIP is mandatory before a full Marketing Authorization Application (MAA) can be submitted in the UK and EU.
• The MHRA’s acceptance of the PIP confirms that the agency has reviewed and approved the methodology of the pivotal Phase 3 trial.
• If the SAP was inherently flawed, MHRA would not have approved the PIP because it is based on the same data and methodology.
4. Statistical Analysis Plans (SAPs) Are a Formalized Requirement, Not an “Excuse” to Deny Approval
• Regulators, including the MHRA and EMA, approve trials based on pre-specified endpoints and analysis methods.
• Any adjustments to endpoints or methodologies are normal regulatory discussions, not an indication that the drug is unapprovable.
• The FDA, EMA, and MHRA have all approved drugs with similar external control arm methodologies—particularly in rare diseases and cancers where randomized trials are impractical or unethical.

Conclusion

HyGro’s claim that the PIP approval was only for the trial design and not the drug is intentionally misleading. The approval of the PIP confirms regulatory confidence in the trial methodology and is a necessary step toward full approval. The advancement of combination therapies does not invalidate DCVax-L’s efficacy, but rather highlights its importance in modern immunotherapy approaches.

At this stage—more than 400 days into the MHRA approval process and with all required inspections completed—the odds of DCVax-L (Murcidencel) not getting approved are extremely low. Here’s why:

1. The MHRA Would Have Already Issued a Major Rejection If There Were Serious Issues
• If there were fundamental flaws in the trial design, statistical analysis plan (SAP), or manufacturing process, the MHRA would not have let the application proceed this far.
• Instead, the application was validated and entered the review process back in January 2024.
• Any serious deficiencies would have resulted in an outright refusal to file (RTF) or a request for major revisions much earlier in the process.
• Given that we are well beyond the standard timeline, the most logical conclusion is that the review has required extended discussions rather than fundamental obstacles.

2. Inspections Are Done—This is Usually the Last Major Regulatory Hurdle
• All required inspections (GMP, GCP, and PV) have been completed.
• If these inspections had uncovered deal-breaking issues, the MHRA would have flagged them long ago and the application likely would have been withdrawn.
• The fact that NWBO has not withdrawn the application strongly suggests that any remaining matters are resolvable.

3. The Only Remaining Step is Likely a CHM Review and Final Decision
• Since the MHRA’s CHM (Commission on Human Medicines) was involved in prior PIP approvals for DCVax-L, they are already familiar with the therapy.
• Any remaining discussion is likely about label specifics, post-market requirements, or minor clarifications rather than outright rejection.

4. The MHRA Has a Strong Incentive to Approve
• The UK has been actively trying to establish itself as a leader in cell and gene therapy.
• The government has invested heavily in regenerative medicine and post-Brexit regulatory independence, meaning they want first-mover advantage on innovative therapies like DCVax-L.
• DCVax-L has been manufactured in the UK (Advent Bioservices), creating jobs and scientific expertise.
• Rejecting a homegrown innovation after such a long review would contradict the UK’s healthcare strategy.

5. Combination Therapies Do Not Make DCVax-L Obsolete—They Make It More Valuable
• Some skeptics argue that DCVax-L might not be approved because the standard of care is evolving.
• However, DCVax-L is already being used in combination trials, including with Keytruda (pembrolizumab) and Poly-ICLC.
• The approval of monotherapy does not prevent future approvals for combination use. Instead, it makes those next steps easier.

6. Long Review Times Are Not Uncommon for Novel Therapies
• Cell-based immunotherapies like DCVax-L are complex, requiring extended regulatory scrutiny.
• Other cell and gene therapies (e.g., Zolgensma, CAR-T therapies) have faced long review periods before ultimate approval.
• The MHRA has not issued a negative signal—just extended the review.

Final Verdict: Approval is the Most Likely Outcome
• Given the long review time, completion of inspections, and no regulatory rejection so far, the most probable outcome - if not the only one - is approval.
• The worst-case scenario at this point is a request for further clarifications or post-marketing commitments, but an outright rejection is highly unlikely.

With over 400 days of review, completed inspections, and no public red flags, DCVax-L is very likely to be approved by the MHRA.

Keep bullshitting HyGro. Work hard for that pay check.