GILD
#<UNK>, I will answer the first question.
We have Phase 2 data.
W had discussions with FDA.
They've accepted our plan so it will be two studies.
One will be, as we call it, a single variable experiment where we compare 9883 to dolutegravir in the background of F/TAF.
And the other one will be a double variable experiment.
We'll compare the two single tablet regimens, Triumeq versus 9883 F/TAF single-tablet regimen.
We hope to enroll the study by the end of this year ---+ start enrollment ---+ so it's all fast-forward.
<UNK>, it's a good question.
We're scrambling right now because I don't have that one in front of me.
It's a fairly recent invention from Gilead.
So, I think it is pretty far out there.
But we will get that number out for you as soon as we can.
Correct ---+ well, 2030.
But you're correct, it is going to be an STR because of the amount of API, the active pharmaceutical ingredient, in that table is, in fact, going to be one of the smaller StRs available.
Mari, it's small, a single tablet regimen.
<UNK>, I'm not sure clinically it will have any advantages.
It had some slight advantages in vitro with systems.
On the first question, we still see, as you recognized in the chart, very high levels of restrictions still through F0 and F1 patients.
And we see this in a formal way in the contracts that we're working with.
But we also see it qualitatively when we talk to doctors where, dependent on insurance company, doctors, I think in some case, don't even bother to write prescriptions because they know they're going to be rejected.
And we do see the rejection rates and some of them are quite high.
But I think we just need to keep encouraging our partners to try and treat earlier and consider treating less sick patients.
And I think as we see these patient flows ---+ and this is pretty much the same answer I gave last time, as well, I'm afraid ---+ but as we see patients flows begin to stabilize and become more predictable, that does work better with the payers and the PBMs' models.
Again, I hope that will encourage them to consider treating people early.
And, of course, finally, they do get much better value, especially for the less sick GT1 patients if they treat for eight weeks.
So we hope all of that will continue to encourage them.
But it is a bit frustrating, I agree with you.
<UNK>, the second part of your question is would the label update from our competitor allow us to go back in the contract.
And I would say that's really not the philosophy here.
I think people who are choosing between us and the competitor have to make decisions on behalf of the plans, their ability to pay and the patients that they want to treat.
And it would really be up to them to look at the level of access that they want to give because, frankly, the 2016 contracts are all in place.
Those have been negotiated and the payers, we've left it up to them to determine the level of access that they would want to give to us versus them, and, as <UNK> pointed out, also the level of access they are willing to give to patients with lower fibrosis scores.
I'm sure every new data set that comes out allows them to rethink a position, but from where we are right now I don't see any major changes occurring.
Maybe I could just add, <UNK>, we are very happy, as I mentioned in the script, there's plenty of real world data sets coming out, and really do, I think, hopefully, give payers the confidence that investing in relatively expensive medicines is worthwhile because of the cure rates and the tolerability and safety profile.
The more real-world data sets that come out, I hope that will be encouraging.
And, finally, yet again I'd say the opportunity to say that Gilead believes in making sure that prescriptions are in the hands of physicians and their patients and not forced upon them by exclusive contracts.
So, all of that we hope will encourage perhaps a rethink.
We are very busy behind the scenes.
In fact, we just had a conference here locally last week with a number of partners that we're working with.
We have a program called Focus.
We have partners with about 100 different external organizations across, I think, 18 cities so far across the US.
And the objective here is increasing diagnosis with various programs around screening and then, importantly, linkage to care.
There's a whole list of programs that we've been hearing about their initial work.
One of the things that is quite surprising, I think, to everyone is that the levels of prevalence, albeit in fairly high targeted areas, have been way higher than people anticipated.
Roughly double, in fact, the numbers that people have expected.
As for the DHSS question, I can't really comment on that.
But there is a lot of work going on out there.
And because, I think, of the simplicity of the treatments and the very high levels of SVRs we are seeing, people are getting more encouraged to address the problem.
The slide you're looking at the top right-hand corner, is the fibrosis scores.
I just want to emphasize the title on the top here.
This is intent to treat, so essentially this is prescriptions that are written but not necessarily filled.
And what we do know is that, although it suggests that half the scripts are F0 through F2, we know that a lot, probably the majority, of those F0 through F1, at least, are not being filled, certainly by some of the payers who are easy to identify.
In the F2 area, it's a borderline situation.
We know this quantitatively.
But, again, we also know it qualitatively through our sales force and our interactions with physicians where it's still quite hard work to get F2 patients through the prior authorization process, and time-consuming and bureaucratic.
So, so it's a situation that's frustrating for everyone.
As I said in my comment just a couple minutes ago, I think that as we see treatment flows becoming more predictable, as we see more real-world data with the products building a higher level of confidence that SVR rates and safety profiles are good, that we hope that payers will start to relax criteria around fibrosis scores and other patient characteristics that we've seen acting as barriers to treatment.
We will continue, as we have done and will do, to talk closely with our payer partners, and try and encourage them to treat more people and reduce these barriers to treatment.
Thanks, <UNK>, it's <UNK> <UNK>.
Just to be clear, when we thought about this product, we thought about it being a better alternative medically for patients of genotypes 2 through 6.
And that includes some patients in the United States but a vast majority of patients who fall in that category are, of course, outside the United States, with Harvoni maintaining as place in genotype 1, particularly because, as <UNK> is alluding to, we have such a very strong safety data set now on Harvoni, including over 600,000 patients who've been treated with sofosbuvir now in various forms, the fact that we have the eight-week option for patients which provides quite a savings for the appropriate patient, and, as we've seen very high cure rates in real-world settings of that eight-week regimen.
So, I do think there's going to be some patients who would benefit from the shortening of duration, not having to go to 24 weeks, in some cases, not having to have ribavirin in other cases, and allowing us to then have a very good option for those patients 2 through 6.
I don't think there's a big warehouse effect of patients waiting for that but I do think this provides a very important option for patients who would want a pan-genotypic option, and for doctors who may not be able to genotype as effectively.
So, I think it's a very important breakthrough for us and will allow us to continue the longevity of the franchise, more so than provide any sort of bolus effect upfront.
I guess there's an implication that we've been out making offers.
I don't think the market really changes all that much dynamically in terms of M&A activity.
So, I cant tell you if people's expectations have changed based on valuation changes.
But I've seen these cycles go up and down over the years, and when there's a deal to be put together and it's timely, it can be done.
So, I don't think it changes the overall outlook for M&A at all.
I think, from my perspective, it's about the same as it was at the beginning of the year.
Hi, Phil, thanks.
First of all, I'd say you see the same data that I see with the weekly scripts.
What you don't see is the non-retail sector, perhaps.
And you may not see what we call NV Rx which is the new to brand, which is essentially the new starts data.
I think that we're fairly confident we've now seen a flattening out of the trend of patient new starts in the US.
As I said earlier, I said a couple times now, we saw a very strong first quarter which really was reflecting the warehousing of patients waiting for Harvoni in the US.
And Harvoni was such a step change for GT1 patients.
But we've had a fairly flat two quarters in terms of patients starting on sofosbuvir products.
In quarter four last year, just to put it in perspective ---+ and Harvoni was already launched then, by the way ---+ we saw about 45,000 patients being treated.
Then we had this big bolus in quarter one, about 70,000 patients.
In quarter two we saw about 62,000 and in quarter three we've estimated about just around 60,000.
So, it's flattening.
And when you add the retail and the non-retail together.
And as I said, as we go into quarter four, I think we can expect that to be fairly stable as we go into next year.
Having said that ---+ and again, from my prepared remarks ---+ I emphasize that we are doing a lot of work across the country and around the world to work with governments and other stakeholders to really try and encourage earlier treatments, more screening, and so on, so that we can extend this hepatitis C business for many years.
And we think that's going to be the case because even now we've treated just a tiny fraction of the diagnosed patients and hardly touched the undiagnosed area in terms of volume and potential.
So, we are very confident of the future.
But 2016 I think will be a more stable year in the US.
I think it is going to be patients working through the system.
But I think we're fairly optimistic that over time, and it may take a little bit longer time than shorter time based on what we've seen so far, those fibrosis scores another patient characteristics which would represent barriers to start treatment will be relaxed somewhat.
And it's self-fulfilling, in a sense, that predictable and stable patient flow works with the business models of the payers.
I think they will start to feel more comfortable about relaxing constraints.
So, gradually we should start to see more patients coming through.
We have to be fairly specific by country.
Looking at Europe in aggregate doesn't necessarily paint the picture.
So, let me just talk you through quarter three what's been happening I think in Europe.
We've seen early launch markets like Germany begin to stabilize at lower levels but more consistent levels.
And that's a parallel somewhat to what we saw in the US.
So, that would be Germany and France, being the early launch markets.
We're then seeing markets which have high prevalence and ambitions to treat a lot of patients, like Spain and Italy, really starting to address their warehoused patients in quarter two, and starting to go into quarter three.
And we've seen, I would suggest, somewhat of a spike in those countries.
And we would expect those going forward to come down to lower levels but more consistent levels.
And then we started to see new markets like the UK coming on stream during quarter three.
A confusing aspect in quarter three in Europe is because there's a very high level of vacations in July and August, not just for patients but for treaters and wholesalers and so on.
So, there's assumed moving parts there.
Going forward I would expect Europe to start to flatten out and stabilize somewhat.
But, of course, as I said, there's different dynamics country by country.
And I mentioned in the script a couple of the smaller countries who haven't even launched yet but we will be launching in the next quarter.
I'll answer the first question, which is the 8-week regimen.
Our estimate is about 40% of GT1 patients in the US, which is similar to last quarter, have been on the 8-weeks regimen.
That hasn't changed too much.
If you look at just the epidemiology and look at the GT1 patients who would qualify for 8 weeks, that's more like 70% of those.
So, I hope that answers that part, and I'll hand you over to <UNK>.
<UNK>, I would say the answer to the 48-week is there won't ben an announcement.
The FDA ---+ we have agreement with FDA.
The endpoint in that study is [HVP3] hepatic venous pressure gradient.
And FDA felt that the 48-week data would really not suffice for approval but we needed 96-week data.
Now, of course, there could be the possibility of some spectacular result like prevention of SEAs or something like that.
Or the opposite, also.
There could be surprise about harm, in which case the DSMB could make the recommendation to either stop the study or unblind it.
But I think that's unlikely.
This is <UNK> <UNK>.
As I said earlier, the contracts have been finalized for 2016.
That always happens earlier in the year.
In fact, we're already starting to talk a little bit about 2017 with the payers.
And they have a range of options.
Much like they had in the past, they can choose what level of rebate they would want to have based on their ability to open up access.
I think 2015 was a bit of a shock to the system with the warehoused patients and, as <UNK> implied, next year we think will be a much smoother base from which we can then try to impact the growth of the overall market.
So, they will have options based on how they negotiate with their clients to open up access or not for next year.
That will be an ongoing discussion with them and within their internal groups, as well, as the data emerge on this.
So, we feel very positive about this in the long term and it sometimes just takes data and time for these things to work themselves out.
No, we're not putting that number out there for the gross to net.
I think one thing, to focus on what <UNK> had said earlier, what we are seeing is a trend toward shorter therapy.
So, a lot fewer use of the 24-week option for patients and then a lot of the 48-week option for those patients.
That is a real benefit driving the costs down by bringing in shorter care to the patients, as well.
So, that's what you would expect as the more sick patients in those categories work themselves through.
You also had a question about competitors coming to market.
We feel very strongly about our position in the market.
We feel very strongly about the value that we've been able to bring and, importantly, the safety database that we have that will give us a very strong position in the market regardless of who comes in in the future.
<UNK>, our thoughts for the triple combination HCV regimen is two-fold.
First of all, we're going to do one study ---+ and we still have to talk about all the details ---+ that will explore the utility of the triple combination regimen to be a universal salvage regimen.
So, whatever you have failed before, whether it's [non-nukes, PIs or NS5As].
There's triple combination nation regimen, will provide a universal salvage possibility.
And the second thing we're exploring is eight weeks duration of therapy in various patient populations.
And, again, we're working with the FDA for all the details of that.
We haven't decided, the final decision has not been made, but those are our two-pronged approach.
And then the other question.
<UNK>, you asked about the VA tailwind and unfortunately we're not able to share any details about prescribing habits or business in the VA, so I can't help you.
<UNK>, I'll answer the first question.
We are not exploring a six-week duration regimen anymore.
And the reason is simply that our experience has been that it works for a subset of patients but not for broader patient populations.
If you look at [seervodics] or treatment-experienced patients, then the response rate (inaudible) are not as high as they should be.
And I want to remind you, you'll notice that the response rate, if you just get 90%, people won't accept that anymore.
It really has to be 95% or more and we're not seeing that across a broad patient population with six weeks of therapy
That was the previous question, <UNK>.
Changing genotypic PI together with velpatasvir, together with sofosbuvir, the triple, is going to be a universal salvage regimen and potential universal eight-week duration therapy.
That's what we're thinking.
But not six weeks
<UNK>, I think your second question was about what Express Scripts might do.
Obviously it's up to Express Scripts to figure out what they want to do, given where they are.
The national formulary where there's exclusivity for the Viekira Pak, of course, is about 15% of the covered lives of Express Scripts.
Obviously we're open to discussions any time they want to call us.
But I have no idea what their thoughts would be, I have no idea how the label would impact their business at all.
That's up for them to decide medically what's the right thing to do for their patients, of course.
<UNK>, I would like to add something.
The six-week duration treatment would still be two prescriptions.
It's not possible to package 42 tablets into a bottle and have that be one prescription.
That's another reason why six weeks is not as appealing.
Eight weeks is also two prescriptions.
Let me just talk a little bit about the HIV franchise.
Actually, one of the encouraging pieces of news in the US is that 8 out of 10 patients now are receiving a single tablet regimen, which I think demonstrates that the concept of single-tablet regimens is really very well-established now.
Triumeq has been doing well on its launch, and has been taking some market share from Gilead, although 7 out of 10 patients new to treatment are receiving a Gilead product and 6 out of 10, roughly, are receiving a Gilead single-tablet regimen.
The conversation in HIV, having been focused somewhat on third agents over the last few years, we feel now is going to come strongly back to the backbone of these HIV single-tablet regimens.
Really up until next week Truvada has been well-established as the standard of care backbone in these single-tablet regimens.
But as of the 5th of November, our PDUFA for TAF, or F/TAF-based regimens, that changes, and F/TAF will be the standard of care backbone for single-tablet regimens going forward.
With the launch of Genvoya next week, we are very confident that we will see a major milestone in the upgrading of HIV treatment.
And, as <UNK> said earlier, because patients are living longer with HIV, have a lifetime of therapy, this is a major improvement for patients and a compelling data set that we are launching both for patients naive to treatment and for switched patients.
And with switched patients it takes time to get patients to switch and it won't happen by itself, but the commercial organization and the medical affairs organization and Gilead are very well-prepared and very motivated and very excited about the launch.
So, we are very confident.
We start enrollment at the end of this year.
Assume six-month enrollment, 48-week endpoint.
That's middle of 2017.
6, 2 months to write it up and submit, and then another 12, 10 months for review.
So, that gets us roughly into mid 2018 timeframe
Thank you, Candace.
And thank you all for joining us today.
We appreciate your continued interest in Gilead.
And the team here looks forward to providing you with updates on future progress in future earnings calls.
Thanks.
