GILD
#You know, I think it's hard to tell on the flow of patients, first of all.
What we do know is there's plenty, plenty patients out there.
As I said, we have ---+ our data, we've got three different sources of data which shows that 25,000 to 30,000 patients are coming into treatment.
Obviously, a lot less than that are actually being treated.
And anecdotally, as I said, I think it's because there's bureaucracy still in the physicians' offices, which give a kind of ---+ you know, I guess that's sort of gating in a sense, the number of patients that can be treated.
And also, it's from the patient's side, you know, people are actually ready to be treated.
I think they want to be teed up, if you like, for treatment; but they might not want to actually start tomorrow morning.
So I think we should expect patient flow to be fairly stable through this year.
And then on the negotiation side, I mean, I think with real-world data, payors are tending now to really take a lot more time and put a lot more thought into evaluating the clinical profiles of the product.
And you know, until we see the clinical profiles of the new products, it's very hard to predict how competitive they are.
I mean, if they are competitive, I think we have to anticipate prices will come down, and we'll negotiate.
Because we certainly don't want to lose any access to patients for our product.
And we'll defend our market share vigorously.
So it's hard to predict.
I think directionally, competition equals lower prices.
But we are going to be focusing on looking at differentiating our product.
We've got great products out there now, and our pipeline looks really exciting.
So I think we're in good shape for a long and sustainable and healthy HCV business in the US.
Maybe, <UNK>, I could take the first part of your question.
This is <UNK>.
We gave guidance for the full year.
I would say, yes, this quarter we had a slightly uptick relative to our HIV expectations and slightly down relative to HCV.
But I think we have still got three quarters to play things out.
And as <UNK> said, we continue to be optimistic relative to patient starts and a more stable, predictable environment going forward.
But it's still very early to tell.
Yes.
And in Europe, I've got to say, the payors are treating the products generally with less consideration to the clinical differences than we are seeing in the US.
And there are some payors who are treating the products a bit more like commodities.
And we are working hard to make sure that we educate them as best as possible.
And I think the real-world data, much of which originates from Europe, is really supporting us in that.
But we have seen some instances of, for example, tenders in the Nordics which have a very binary outcome.
And there are certain times that, you know, we've decided that those tenders' prices don't warrant the value of our product.
So our market shares have been a little bit less than Europe.
And specifically, to answer your question, I think all three players are out there in Europe trying to get business.
But at the end of the day, we hope that people will recognize that the Gilead products are highly effective, very simple, very tolerable.
And the real-world data, which is now ---+ you know, there's vast amounts of it ---+ really does support us when physicians make their choices.
And as I said earlier, where physicians have the freedom of prescription, we've tended to have very, very strong market shares, in the 90%-plus.
So, <UNK>, actually it's four products that we have currently in early clinical studies, if you include the Nimbus compounds.
That deal, by the way, has not closed yet.
But it should close in the next week.
So we have the ASK inhibitor, the ACC 1/2 inhibitor, the simtuzumab, and then the FXR agonist.
And we could by the end of this year be in four Phase 2 studies, really, you know, in NASH, to look at the effect of any one of these agents by themselves.
And then we would also at the same time look at our star combination studies to see ---+ you know, too, we always have said we believe in the three points of [PET] disease pathogenesis.
There's fibrosis, inflammation, and metabolic.
And we now have agents that address all of them.
And we're absolutely ---+ our hypothesis is that ultimately it's a complex biological disease and probably more than one agent will be needed.
And we're looking forward ---+ maybe sometime next year we will then go to Phase 3.
With regards to BD, we're of course looking.
At the moment there is nothing out there that I would say we have to get ---+ as I said, we have four components.
We are going to look at those individually and then, as the results come in, make decisions what else we would need.
I would say, <UNK>, so we have, as you know, 4774 ---+ 4779, that's the GlobeImmune vaccine.
We presented data at last AASLD showing that at least in virally-suppressed patients, it did not lead to a reduction in its antigen.
We are currently doing a study in treatment-naive patients.
We then have 9620 to [deal our seven] agonists in Phase 2 as well or Phase 2a.
And then we have two other internal programs that we haven't disclosed yet.
They are pre-IND, but we have identified with two different mechanisms, molecules that we want to develop or evaluate in human clinical studies.
But having that said, it's early ---+ I mean as a general statement ---+ in hepatitis B cure.
And we are really having a very open mind and looking outside: what else is there potentially that would fit our portfolio.
I think, broadly speaking, your math is correct on that.
It's hard to tell exactly where the patients are coming from.
But I think mathematically that sounds about right.
Sorry, what was the second question.
Oh, yes, sorry.
Eight weeks ---+ yes.
We've drifted slowly but surely upwards on the eight weeks.
I think were about 43% now.
I've got to emphasize: the data we have is called intent to treat rather than actual prescriptions.
So the intent to treat in the US is about 43%.
The epidemiology, as we previously said, we probably suggest about half genotype 1 patients would fall into the criteria that would trigger off eight-week treatment.
We're not going to break down the weeks of therapy.
I mean, I just said what we think the eight-week amount is.
But the rest of you'll have to just model yourself.
And I'll hand it over to <UNK> for the second question.
So, <UNK>, as you know, steroids FXR agonists do many, many things, not only in the liver but in also other target organs.
So our philosophy is that we have an FXR agonist that purely acts at the level of the G.
I.
So it does not get totally absorbed to any meaningful degree.
And then what it does ---+ at the level of the G.
, it releases FGF 19.
And we believe that FGF 19 does everything that it needs to do in order to impact on NASH.
That's our hypothesis, and we are testing that.
And we should have data available in the fourth quarter of this year.
So that's a fairly easy experiment to do.
You simply look at bioavailability, which is below, but the FGF ---+ might increase the FGF 19 levels with some of the consequent metabolic effects.
That way we also think we can prevent pruritus.
We can prevent the cholesterol effects.
We can prevent alkaline phosphatase elevations, et cetera.
And so if this all is true, it should be a much safer and cleaner FXR agonist.
We could probably have some of the preliminary data at AASLD, and we would then move into Phase 3 soon after that.
So we're not that far behind other companies.
I don't have a lot of details at my fingertips, actually, <UNK>.
I would say, just to build on what <UNK> was saying earlier, the interactions we are having with many people working on diagnosis projects around the country are that there's a lot of ---+ a surprisingly high level of positive diagnosis in some of the urban centers, and in the ER rooms in particular in those urban centers, where diagnosis rates have been double at least what even the local investigators have anticipated.
Why that is, I'm not sure.
But this has been consistent throughout the country.
So I would say that diagnosis rates, the 200,000, would grow rather than shrink, certainly for the next few years.
And there's great efforts, of course, now to encourage diagnosis, because people know that at the end of it, they're going to be treated and have a high probability of being cured.
Yes, so <UNK>, you're exactly right; there have been previous ACC programs at Merck and Pfizer.
They have not been successful, and the reason had to do with the specificity.
This compound is really unique.
It's a low nanomolar inhibitor of both ACC-1 and ACC-2.
It then inhibits not only the pathway that goes to the [nova like progenesis], so no coenzyme A production; but it also inhibits at the level of the mitochondrion.
It stimulates, I might say, lipid acid beta oxidation.
So it does really two things.
It inhibits the formation of lipids, palmitate mostly, and at the same time it stimulates the beta oxidation of lipids.
And so there has been some anecdotal reports from the Pfizer compound that inhibition of ACC-1 and 2 results in a decrease in liver fat.
That's, by the way, something we would do as one of the next experiments.
We would look by MRI on reduction of ---+ we have already shown at the EASL presentation that it inhibits lipogenesis.
Now we have to show also that it inhibits lipids fat content of the liver.
It's a very straightforward and easy experiment to do.
And I think once we have shown that we have pretty high confidence, that there will be a meaningful clinical benefit of the compound.
Thank you, Candace, and thank you all for joining us today.
We appreciate your continued interest in Gilead.
And the team here look forward to providing you with updates on our future progress.
