Vical ran a Phase 3 trial in melanoma testing Allovectin-7 (A-7).
The primary endpoint was durable response rate (DRR) and the first secondary endpoint was OS.
The trial was designed to seek AA on DRR. Confirmation and conversion to full approval was going to use OS from the same trial.
Very similar to the NWBO situation.
While the trial was underway 3 new melanoma therapies were approved. One of them received full approval: Yervoy.
Now, of course Yervoy becomes an “Available Therapy” and that takes AA off the table for A-7.
What does Vical do?
Rather than stop the trial and analyze DRR when they originally planned, they let the trial run (still blinded) until they reached the target OS events for the secondary endpoint - about 2 years later.
This was done with the FDA’s concurrence - they had a SPA with the agency.
So this is my prediction: Consistent with Dr. Liau’s comments, they are going to wait until they reach the target 233 OS events before they unblind the trial data.
The OS results will be a comparison between early and late DCVax administration.
(And this has nothing to do with the “Available Therapy” issue and everything to do with the methodology of determining PFS events in the Phase 1 trials.)
Can I prove it? Nope, it’s just a hunch. It is what I would do if I had a say in it (which I obviously do not).
LP gets to keep the gravy train going to Cognate, that‘s a plus.
Remember, when the “enhancements” were made, the OS target went from 72 events to 233 events. They were originally targeting a 17 month improvement in OS, after the enhancements they are targeting an 8 month improvement.
LP made a big deal about PFS going from detecting a 6 month to a 4 month improvement, but the real substantive change was in OS. And that was likely done to try to account for the confounding affect of x-over (will it be enough?).
And, as Dr. Liau said: They are now comparing early vs. late DCVax, a comparison that can only be made by evaluating OS.
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Oh, and as for Vical? The trial failed. Despite the militant longs cheering how it was such a sure thing, A-7 patients had worse survival than control. Yes, all those morons who posted on the patient websites encouraging patients to get in the A-7 trial because the earlier data was just so incredibly promising, actually may have contributed to the early death of patients.
And what did the longs do next? They sued Vical of course.
The case was finally dismissed this week. The judge ruled:
“Ultimately, investments in experimental drugs are inherently speculative. Investors cannot, after failing in this risky endeavor, hedge their investment by initiating litigation attacking perfectly reasonable—if overly optimistic— statements proved wrong only in hindsight. At all turns, Defendants clearly stated the bases for their opinions and denoted them as such. Punishing a corporation and its officers for expressing incorrect opinions does not comport with Rule 10b–5’s goals. Accordingly, the Court GRANTS Defendants’ motion to dismiss. “
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And as for Cherry Tree’s response….
I said Dr. Liau said they “are now comparing early vs late DC vaccination “
And Cherry Tree makes the claim that I’m wrong and what she really said was: “we are really comparing now is early DC vaccination vs later DC vaccination”
Too funny. Are you being serious? What’s the difference?
Cherry said: “It is hard to believe the if all the patients are living longer because the FDA insisted on a crossover that they would not approve DVCAX-L. What possible motivation would they have to deprive GBM patients from an effective treatment”
I don’t think you understand how this works. The FDA is mandated, by law, to demand substantial evidence of effectiveness and the law specifies that this evidence must be derived from adequate and well-controlled clinical investigations.
The “motivation” to deprivc GBM patients? How about their fear of approving an ineffective drug. The data on Allovectin looked pretty darn good. When put to a rigorous test it killed people faster than SOC. That seems like a pretty good reason to demand “substantial evidence”.
As for your “FDA insisted on cross-over” comment: They insisted on cross-over because PFS was the primary endpoint. The FDA did not insist that PFS was the primary endpoint.
Did the FDA insist on x-over for Celdex?
Did the FDA insist on x-over for IMUC?
Of course not. Because they chose OS as their primary.
When I hear people touting this FDA insistence on x-over it sounds like they think the FDA was so impressed with the results of the 20 patients a decade ago that they just had to help usher in this new miracle cure. That’s laughable.
Crossover is in the trial because the primary endpoint is PFS.
If OS were the primary endpoint the FDA would not "insist" on cross over.
Whose bright idea do you think it was to make PFS the primary endpoint?
Do you realize that in the AVAGLio trial in the same indication that PFS and OS were co-primary endpoints but OS was the registrational endpoint?
Cherrytree: “and your allegation about the temporary screen halt (not partial clincal hold as you phrase it) are unsupported”
LOL. Unsupported? As I phrase it? Have you seen EVERY SEC filing since September?
“…… which is on a partial clinical hold in regard to new screening of patients”
You better read them. They are going to throw it back in your face when you sue them. That's their disclosure right there.
That's it, 3 posts and out. If I have anything to add you know where to look
AI
