Tumor shrinkage is a good indicator of efficacy, precisely that was the goal accepted by the FDA and that Imcl failed to provide evidence and showed poor execution of accepted protocol, therefore the FDA facilitated a lot to Imcl who failed, and seemingly ABUSED with the silence of the REAL concerns raised by the FDA long before the RTF, during the execution period of trial.
I am not accusing anyone, the RTF copy (that Imcl has not denied) mentioned the pitfalls, the most damaging was the BREAK of the inclusion/exclusion guidelines, this problem more than anything else was the most damaging to the point of destroying any evidence of the drug efficacy.
How did the FDA find that there were 21 deaths instead of the 3 reported by Imcl (all deaths within one month of completion of participation by a subject was reportable) and why did Imcl failed to report accurately? Well, the FDA oversees trials and has the enormous job of collecting their own data on many aspects of trials independent of company research.
If in a trial the researchers carefully choose the subjects according to survival expectation and use concurrent controls it is often well done that even 6 months survival difference could be established.
Imcl was given "fast track" review, given Rolling BLA, acceptance of a phase II with not blindness, no placebo control (historical control was the agreement)given guidance over time about mistakes, a relatively small sample size (120 subjects) and survivability not a requirement a "surrogate" endpoint that is tumor shrinkage was the endgoal and with all those concesions Imcl performed so poor that the trial data is not suitable even for review, REJECTION OF APPLICATION is the worst grade they could get for a drug in clinical stages.
Chances that the rest of the studies are better and could bring the necessary evidence are just a MAYBE.
So far no evidence the drug works! |
