RE:RE:RE:NGM trial fail. A commercial decision???Great info - thanks! I suppose another reason for the delay on NASH, which I guess you are alluding to, is they may have been in consultations with a NASH partner all this time and are working with them on the details of the protocol with the regulators. If all ends up in the right spot with the regulators, perhaps the potential partner will be happy to become an actual partner in NASH and an announcement will be forthcoming about not only the finalized protocol but also a partnership arrangement to pursue the phase III trial. Of course, this is all just wild speculation but maybe the potential partner has certain requirements for the protocol and THTX has been hard at work to meet those requirements in their negotiations with the regulators so they can share the very heavy burden of a phase III NASH trial with someone else. That may explain the delay in getting the trial going.
qwerty22 wrote: Red
SPCEO1 wrote: A few points from this:
1.) Part of the reason for not going ahead was speculated to be because NGM's drug was an injectable versus MDGL's pill. That is certainly a concern for TH as well, but TH's pen should make using Egrifta it a bit more tolerable.
I think rather than separating out one factor, like injectable, what they were talking about was the overall drug profile. It's that overall profile - safety, injectable, anti-fibrotic etc etc that they don't particularly like. In previous podcasts they've developed an idea of how NASH treatment might work. They think people will go on 'aggressive' drugs initially that rapidly cut liver fat and biopsy endpoints to quickly move things in a positive direction, they think these drugs can have some negatives like injectable or poorer safety profile. After a certain time, or certain improvements they think patients might switch to a more benign, oral drug that keep people in a healthier state, a bit like what statins do for cholesterol. The point they made in this podcast is they think alderfirrin slips between those two categories. Injectable is clearly not optimal but I don't think they think it kills off a drug, it depends what the rest of the drug profile looks like. 2.) I think Harrison said that even the same person reading the same biopsy result a second time came up with different readings! No wonder NASH has become a drug graveyard if that is the case as results are so inconsistent in part due to this factor. Committing a ton of money to a phase III when the outcome is impacted by such variability in biopsy readings would be hard to do.
Issues like this are all being discussed in a background of only failures. I do think a success is going to allow a better reasoned argument. There was a study last year in why 9(?) different Nash trials failed. Biopsy reading came up as a possibility. But there was almost as many other possible explanations for failure as there were trials. The discussion about NITs (non invasive tests) was pretty positive, maybe the one positive from this is it'll add to the pressure on the regulators to move away from biopsy. 3.) Someone quoted a cost of $250-$300 million for a phase III NASH trial! I hope they got that wrong as TH cannot afford that.
Maybe this is for all the way to the end of Ph4. NGM abandoning F2/F3 NASH is a positive for TH as it was a worthy potential commpetitor and the door is still wide open for TH. But there were some concerning things said in that talk for TH's NASH program. I have wondered if the slow walking of the start of TH's NASH phase III until the third quarter of 2021 was tied to the board's hoping they would have great cancer results by then and could also make a commercial decision to redirect all available cash to that indication and leave the drug graveyard of NASH for others to try to exploit.
Yes that is definitively a possibility. One of the initial thoughts I had when THTX announced the study may proceed letter was even though they weren't immediately proceeding I did think that having the letter essentially removed the FDA as a barrier to the program going forward and that really it was all now in the hands of THTX, I couldn't understand how the fda could walk back from that letter without new data to change their mind. So really the decision not to proceed was all THTX ( I'm ignoring how the EMA fits in for now). So yeah THTX are slow walking this in my view, the question is why. Weighing up the best place to put resources with cancer data in hand is as good an explanation as any.
You know I'm stuck on the "oddness" of the NASH program for a number of reasons. When I think about where this will go I land on all sorts of possible outcomes both positive and negative, most fanciful. For example I hope a pharma likes the idea of a late-stage NASH program and appreciates the data and steps in to take the financial risk (maybe that's the package they've been trying to put together all along), I think about all sorts of adaptive Ph3 that lead to an interim data readout that the market can invest in, or as you say THTX abandoning NASH to focus on a cancer program with Proof of Concept. The one thing I really struggle to imagine is a cookie-cutter Ph3, supported by both regulators, run by THTX and financed by an enthusiastic market. The only thing keeping that on the table for me is Paul's insistence that they will be dosing patients in the Fall.
It could surprize us exactly what sort of investment story emerges in the next 6 months, something quite different to what we are all imagining.
qwerty22 wrote: This 25 min discussion is well worth listening to.
The suggestion is the trial didn't really fail clinically but NGM made a commercial decision because the company couldn't see a position for the drug in the market. Seems like a pretty brave decision for the company to make to pull the plug at that point. It's worth listening to the end, it sounds compelling to me.
https://surfingnash.com/s2-e28-special-episode-what-can-we-learn-the-aldafermin-discontinuation-in-f2-f3-nash/ So it shows what a negative impact this fail was for the whole NASH sector in terms of the reporting but if you accept this argument then clearly it shouldn't have been.