RE:RE:RE:RE:RE:RE:Mischaracterization of the FDA processIn my opinion, what it signals is just the simplest, as Occam's razor posits: that agreement on the principle of a Phase III was reached by all involved parties (including EMA), hence the clear communication about filing for Phase III in Q4, but disagreement remained on technicalities (and that's hardly surprising), so they did not have any specific pledge of acceptability of the then current protocol to provide.. In other words, sit back, relax, while the scientists are working out the last kinks. I have very high conviction that the real binary event regulatory wise already happened last September and just wasn't accepted by the market. Undisputable facts such as the trial opening for recruitment and first patient being dosed will put all this angst to rest in the blink of an eye..
qwerty22 wrote: So you're suggestion here is they've had all the pre-IND meetings with the FDA, got to a consensus position between the two sides and now all that's left is the technical issue of filing the IND? The Ph3 announcement is de facto a declaration of this consensus position?
My question is why haven't they clearly communicated this? As an example here is Akero's statement describing exactly that position.
https://www.prnewswire.com/news-releases/akero-therapeutics-to-continue-efruxifermin-development-with-innovative-adaptive-phase-2b3-clinical-trial-design-based-on-fda-written-guidance-301137157.html
This is pre the IND submission.
They have analysts clearly expressing their uncertainty about where is program sits in the regulatory program and they have a very clear way to answer that issue by referring to the consensus they've reached with the regulators. Why aren't they doing that? Why did Paul mumble something about shifting landscapes when he could just say what Akero said.
"Akero Therapeutics, Inc. ......... today announced that written guidance from the U.S. Food and Drug Administration (FDA) enables the company to implement an innovative combined Phase 2b/3 study design for pivotal efruxifermin (EFX) trials in NASH patients.
..........
"We are pleased that the FDA found our overall proposed adaptive Phase 2b/3 development program to be acceptable, and we are grateful for the additional clarity the agency provided as we finalize our study protocol,"
Spartrap wrote: Well the uncertainty is: we have no news of the filing itself, and the CEO was spotted saying the dreaded "in the coming weeks" again just a week ago or so.. So polishing/harmonizing that protocol is for sure taking very long. But I don't see much uncertainty in it. It *is* going to be a P3 since they announced it, and it's almost as good as a done deal the moment we learn it's been filed.
SPCEO1 wrote: From how you describe it, the fact that they are filing a protocol means the the FDA is already basically in agreement because of the pre-IND negotiations. Which is why the company expresses confidence and the board of directors has signed off on this project. But there must be some uncertainty still or the company would likely have communicated that it is a done deal already - right?
Spartrap wrote: I'm sure they want the FDA to be in agreement, but this is the role of pre-IND consultation programs, it doesn't affect the timing once the filing is done. I just mean to say: there is no big "decision" or "approval", just a remote possibility of the FDA walking against it's own guidance by answering by a Clinical Hold before thirty days.
SPCEO1 wrote: While it is true a company can start a trial without the official approval from the FDA, uner the circumstances of TH's NASH phase III, I suspect the management and board of directors of TH would like to know the FDA is on board with their approach before spending $70 million or more to do this particular trial. I imagine they would want some indication that this trial would be viewed as a trial that could lead directly to an approval (followed by the phase IV trial to confirm). So, having the FDA being in agreement with what the company wants to do is critically important I suspect, even if it may not be technically required.
Spartrap wrote: I've read many times on this board, that we have to wait for the FDA decision about the filing for Phase III, that this may extend past a month. I think this is a mischaracterization of the FDA process. The filing we are talking about, unless I'm mistaken - and I'd love to be corrected then, is a Commercial Investigational IND, which includes many parts, among which a protocol for trial. The FDA doesn't have to explicitly validate it for it to take effect: it's automatically valid 30 days after filing if the FDA doesn't say a thing. So essentially, it's opt-out, not opt-in, and conversely, the FDA *may optionally* give it the get go before the end of the 30 days. See: https://www.fda.gov/drugs/investigational-new-drug-ind-application/ind-application-procedures-overview Quote: "An IND application may go into effect: -30 days after FDA receives the application, unless FDA notifies the sponsor that the investigations described in the application are subject to a Clinical Hold; or -on earlier notification by FDA that the clinical investigations in the IND may begin. Once an IND application is in effect, a drug manufacturer may ship the investigational new drug to the investigator(s) named in the application."