Appreciated very much for your well-thought out replies biosectinvestor. I understand where you are coming from. Yours is obvious a possible reason, though I think it may be somewhat a stretch.
There are different perceptions and perspectives on the same issue of pseudo progression from different parties. At the time of the partial halt, pseudo progression was already a known phenomenon for NWBio, clinicians running the trial, and regulatory agencies. The problem is when it happened to a patient there seemed to having no ways to distinguish either right on the spot or very shortly the event was in effect due to pseudo progression. So for the regulatory agencies, they had to assume it was a disease progression upon it was approved otherwise; for NWBio it could argue such events were most likely and mostly pseudo progressions, suggested by the underlining patients as a whole have instead lived longer than the rest of the patients in aggregate. So despite seemingly quick disease progressions (one characteristic for pseudo progression events) , these patients have also lived longer than those patients who have experienced disease progressions later (after the exclusion of rapid progression patients from the trial during the 3-month screening process, a characteristic for true disease progression events) which obviously contradicted to the known fact that disease progression normally correlates to underlining overall survival, i.e., the more delayed in disease progression, the longer the overall survival of underlining patients.
In light of the above, I don't think FDA when it initiated the partial halt would consider the halt a straight-forward safety halt. It might just want to give the company time to fix the problem or later provide it with more persuasive and convincing data that would indicate most such suspected events were indeed not harmful to the patients who have experienced the events. Since the halt was lifted by FDA, I do think NWBio was later able to provide to the FDA such data which not only has it showed the underlining patients have lived longer, but they also have experienced better quality of life.
It is in this sense and circumstance I also don't think the partial halt had anything to do with safety at the time. Today it can be said with almost certainty that both NWBio and FDA are on the same page regarding pseudo progressions, i.e., the more than expected disease progression events experienced in the trial are indeed mostly due to pseudo progressions; and it is also suggested NWBio may have found ways to distinguish between pseudo progressions and true progressions, evidenced by the listed second secondary endpoint in the now revised SAP, i.e., cPFS.
All in all, pseudo progression may be a strong indication that DCVax-L is not only safe by also very efficacious. It causes no harm to patients; instead it is a blessing.
GL and best wishes !
[There are not posts left for me today. Thank all]
AI
