Welcome to the Sanofi Q1 2017 Earnings Results Conference Call and Live Webcast. My name is Emma, the Chorus Call operator. [Operator Instructions]. The conference must not be recorded for publication or broadcast. At this time, it is my pleasure to hand over to Mr. George Grofik, Vice President, Head of Investor Relations at Sanofi. Please go ahead, sir.

Good morning and good afternoon to everyone on the call. Thank you for joining us to review Sanofi's first quarter results. As usual, you can find the slides on this call on the Investors page of our website at sanofi.com. Moving to Slide 2. I would like to remind you that information presented in this call contains forward-looking statements that involve known and unknown risks, uncertainties and other factors that may cause actual results to differ materially. I refer you to our Form 20-F document on file with the SEC and also our Document de Référence for a description of these risk factors. With that, please advance to Slide 3 and let me introduce our speakers on the call today. With me are Olivier Brandicourt, Chief Executive Officer; Jerome Contamine, Executive Vice President and Chief Financial Officer, as well as David, Executive Vice President, Sanofi Genzyme. Also joining us today for the Q&A session are, Olivier Charmeil, Executive Vice President, General Medicines & Emerging Markets; Peter Guenter, Executive Vice President, Diabetes & Cardiovascular; Karen Linehan, Executive Vice President, Legal Affairs and General Counsel; David Loew, Executive Vice President, Sanofi Pasteur; Alan Main, Executive Vice President, Consumer Healthcare; and Elias Zerhouni, President, Global R&D. First, Olivier will discuss the key highlights of the first quarter, then David will provide an update on our immunology franchise. After that, Jérôme will review Sanofi's financial results before we open the call to Q&A. Before we start, I'd like to remind you that as of the start of 2017, Sanofi's financial statements include the impact of the acquisition of the Boehringer Ingelheim's Consumer Healthcare business, the divestment of our Animal Health business and the termination of the Sanofi Pasteur's European Vaccines JV. In order to help you compare sales growth rate on a like-for-like basis, we will be referring to growth at both cost exchange rate and at constant structure. This has been noted in the slides at CER/CF. And with that, I'd like to turn the call over to Olivier.

Thank you, George. Good morning, good afternoon to everyone and welcome to our first quarter earnings conference call. So before I turn to the results in greater detail, I'd like to highlight the impact of the changes in structure that took effect this quarter as they had a distorting effect on sales growth. With this in mind, Slide 5 provides a bridge to demonstrate the like-for-like sales growth of the company. If we add back the €384 million of sales that would have been generated in Q1 2016, if we had owned the BI brands and European Vaccines, then our first quarter sales growth at CER and constant structure was 3.5%. On the same basis, our growth rates in the previous two quarters was approximately 3%. This consistent growth trend speaks to the strength of our diversified business model. On Slide 6, I'm pleased to report that Sanofi has delivered an encouraging start to the year, with a benefit of structural changes, our first quarter sales grew by 8.6% in CR to reach €8.6 billion. Our business EPS increased by 3% to €1.42. As I mentioned, sales growth was 3.5%, if we also adjust for constant structure. Our business EPS performance was particularly encouraging as we faced significant headwinds in the quarter from the loss of Animal Health contribution and from a higher tax rate. We managed to more than offset these negative factors as a result of solid underlying sales momentum and the benefits from simplification of the organization which as you know, is a key element of our 2020 Strategic Roadmap. Here, you can see that on Slide 7, that 4 of our 5 global business units delivered growth in the first quarter which more than compensated for a decline in our Diabetes and Cardiovascular units. The highlight,…

Thank you, Olivier. And it's been a privilege to lead this business over the past 6 years and leave it in the very capable hands of my colleague, Bill Sibold. So I know there's a tremendous amount of interest in the immunology franchise which is launching and so if we turn to Slide 16. I'll remind you again that as Olivier has said, this is truly a pipeline and a product and we're approved for atopic dermatitis. I'll update you on the launch in the next slide. The asthma Phase III trial is fully enrolled and again, we hope to be filing by the end of the year on that indication. The nasal polyposis indication at Phase III trial is enrolling and we look to have data from using eosinophilic esophagitis trial again coming out this year. I think the biggest challenges we have in helping physicians think about this is to get the dermatologist to think about it co-morbidities to get the pulmonologist ultimately when the asthma medications approved to be thinking about atopic dermatitis and nasal polyposis. And so again, it's a paradigm shift for medicine. So if you turn to Slide 17. I'll provide you some background as to where we're on the launch with the major caveat that it's extremely early. I'm going to provide some numbers that we won't be updating on a regular basis going forward. But obviously, absent significant insight into our revenue stream at this point, I think these numbers are important for you to understand how the launch is going. Overall, very positive about the how the launch is going. From an operational standpoint, we shipped within the first 24 hours, the sales force reimbursement teams, medical affairs that are in the field, all that is working well. And operationally, we…

Thank you, David, for this presentation. I will go quick, where we're on the financials. And now on Slide 20. So before discussing the details of the P&L, I would like to again to highlight that the [indiscernible] changed compared positively this quarter to our reported first quarter figures, clearly, in contrast with 2016. This was expected. In total, currency movements added 2.5% or €194 million to reported sales on 3% of $0.04 per share to reported business EPS. So latter has contributed to this positive effect, as expected, again, with the U.S. dollar. Now I'll move to Slide 21, looking at the P&L of the reported basis. Sales were just over €8.6 billion, representing 8.6% growth at constant rate. Again, this includes the impact of acquisition for CHC as well as the contribution of our vaccine European business. You can see on the slide a few items which complicate the picture, as already mentioned, that because the tax rate of the quarter was higher than the low tax rate we had for the first quarter of 2016 which was 22.6%. I just confirmed here that for 2017, we continue to expect the tax rate in the 24% to 25% range. Second, we have no net income contribution for our divested Animal Health business this quarter as compared with the contribution of €171 million last year for the same quarter. Taken together, it reduced our growth at the business net income level to 1% in the quarter to €1.8 billion. Against this, we're fully offset the headwind of Animal Health divestment and share repurchases, the consequence of business EPS grew by 3% to €1.42. I now move to Slide 22 to give a clear picture of the ongoing business. We're just here providing that P&L at constant exchange rates but…

Thank you, Jérôme. So just to summarize our position. We think we continued to execute on our 2020 Strategic Roadmap. Our first quarter results benefited from our diversified business model and from the simplification of our organization. We now have a global leadership position in CHC and the integration of the business is proceeding well. We're managing our way through a tough U.S. payer environment in Diabetes. At the same time, we're fully focused on delivering successful launches from our exciting new Immunology assets and progressing the next wave of pipeline innovation. And with that, I would like to hand over to George to start the Q&A.

We will now open the call to your questions.

[Operator Instructions]. Your first question comes from the line of Mr. Florent Cespedes from Societe Generale.

So two questions. First, for Peter. Could you tell us if you have retained some prescriptions from CVS in the U.S. or if there is a message which to the biosimilar or the novel products in the U.S.? And if not, what is your strategy to potentially come back on some formularies? And maybe a follow-up question on your strategy regarding stimulus [indiscernible] and my second question would be for Olivier. Just to confirm if there is anything new regarding your strategy or M&A strategy and if you're still looking for opportunities?

Thank you, Flor. You want to start, Peter? Yes?

Yes, sure. So first on your question on the retention on CVS. So you remember, we put into place a $10 co-pay strategy for both and Toujeo and we're relatively satisfied with this co-pay program because we have been able to retain in total CVS 55% of our volumes. Now remember, CVS is actually composed of 2 sub-pockets, if you will, the national template and then you have the custom plans, both account for roughly €20 million commercial lives. And out of the custom plans, actually, so out of that €20 million custom plans, we have been able to retain 70% axis as such for Lantus and Toujeo. So in total, 55% retention of TRxs and if you would then drill it down to the national formulary of CVS commercial, where we totally lost access, so we only have the couponing strategy as a mitigation strategy, there we were able to retain 43% of the TRxs. So if you compare this with benchmarks, I think it's fair to say that our couponing program has been relatively successful. Your follow-up question on lease, as I mentioned, already last quarter, so we have been submitted the file in Europe and the MA has accepted the file for evaluation and for concerns in the U.S. for competitive reasons, we cannot give any additional background on that.

Thank you. Thank you, Peter. So to your question regarding M&A. Yes, I can confirm that nothing has really changed. We're continuing to focus on creating value for shareholders. Our main driver -- main drivers are the strategic fit as we presented in November 2015, right? So looking at strengthening our business in IRTAs where we have already some level of leadership or others where we're looking at building competitive positions and that is MS, oncology, immunology and CHC. When it comes to value creation to shareholder, we said it also last time, we want to remain financially disciplined and we're solidly looking at deals where we strongly believe we can achieve a return on invested capital exceeding ROI. And finally, driver is of course the pipeline because Sanofi pipeline has been significantly strengthened over the last few years, but we believe our R&D capabilities could be further enhanced.

The next question comes from the line of Mr. Graham Parry of Bank of America Merrill Lynch.

So firstly, on Diabetes, could you quantify the incremental volume loss that we should expect in the second quarter from the UnitedHealth contract, taking in any incremental impacts from CVS that you were referring to? And any initial 2018 contracting commentary you can give us, how that's going, how you're prioritizing pricing versus access, especially given the need to get Soliqua access, too? And then secondly, on the Praluent, if you could just give us a feel for what's driving the delay on ODYSSEY, is that just an event rate update happening slower? Do you think you can still get this data in time for ACC and in time for 2019 contracting negotiations?

Thank you, Graham. So the first question, for you, Peter and the OTC question for Elias.

Yes, Graham, so thanks for the question. And the number of lives in United commercial is actually 60 million. So this is less than, for example, the CVS commercial lives, 40 million. You should also know that Toujeo was not covered at United, contrary to Lantus. And of course, we were in a Tier 3 position, so we suspect the impact of United to be less important than the impact of CVS. So your question on 2018 contracting, of course, it is very early to comment on that. As you know, we have, of course, submitted our bids. And we'll have to wait until we get the results of those bids. And in terms of prioritization, we, of course, have a strategy of keeping a large coverage for many reasons, not only for Lantus and Toujeo, but also in the future for Soliqua. I think the Praluent question is for...

Yes, Graham, for OTC, nothing has really changed. As you know, it's an event-driven trial. And we do want to absolutely perform this trial in the best possible way because I think it's critical for the field that we accumulate the best scientific experience and data to enlighten us in terms of the value of PCSK9. So we were hoping, as you remember, to complete all of the events by models that we had by the end of the year. It's clear that we will be able to recruit all the events by the end of the year. But then you have a certain amount of time to analyze that data. On your question about ACC, we're making every effort to be able to present at the ACC. But because it's really beyond our control where the events are and their adjudication, I can't promise. But that's my hope.

Okay, so no change at all in the number of events or follow-up [indiscernible] the study there?

Absolutely not, no.

The next question comes from the line of Vincent Meunier of Morgan Stanley.

Three questions, please. The first question is on Diabetes. So you've clearly highlighted the deeper decline expected this year in Diabetes and particularly for the remainder of 2017. Has anything changed recently which would make you more cautious? Or is your message today just to reiterate what you said before? Because my feeling is that your tone today is a bit more cautious than before. The second question is on Multiple Sclerosis. Can you comment on the pricing trend for Aubagio and also the price environment in MS in general going forward? And the last question is a follow-up on strategy. The follow-up question on M&A, I mean, you said earlier that you might continue buyback and renew buyback if you're not in a position to find a suitable target. Is it still a valid comment?

All right. Thank you, Vincent. On Diabetes, I don't think there is anything new that we're trying to convey today. We just wanted to highlight the Q1 results, the equation of that good result is it was a minus 6% result and it's minus 15% in the U.S., offset by a plus 12% or 13% in China. So we have that momentum in China. Are we going to see that for the rest of the year? We're not entirely sure. And then in the U.S., the indication is what we're trying to convey. We have these formulary decisions which we learned in last August regarding UnitedHealthcare which has not had any impact during Q1. And we see that during the rest of the year, in addition again of CVS which was only partially, had only a partial impact in Q1. And I think maybe, Peter, you can also provide more color around how much more prescription do we have in the government channel, like Medicaid and if you want to add color around whether or not that has changed versus what we conveyed in the past.

No, I think overall we can say that we're actually in line with our expectations. I think you mentioned the 2 key points, Olivier, of the reasons of the deceleration in the U.S. that we forecast in the year-to-go which is, of course, a full impact of CVS. The first quarter was only a partial impact, right? It started to slide actually as of the last 1 or 2 weeks of December. And then we have the additional impact of UnitedHealthcare. It is true that the channel mix remains unfavorable but not more unfavorable than we have anticipated. But of course, as the year unwinds, you get more sales in unprofitable channels. So it's normal in your net sales that you get an acceleration of the decrease. And perhaps the last piece we can provide is that we stick with our long term guidance of minus 4% to minus 8% and CAGR, 15% to 18%. But we also remind you, like we reminded to you in the last quarter, is that for the year 2017, we will be probably below the lower end of that long-range guidance.

Okay, thank you, Peter. David, do you want to answer the Aubagio question?

Yes. So with regard to pricing, I mean, we all know there's much more focus on pricing in the U.S. overall, so it's obviously a point of debate. I think with regard to the MS class specifically, it is part of that discussion. Fundamentally, nothing has changed as of now. The things I'd remind you of is Aubagio itself is the lowest-priced oral with further discounting off the WACC, of course. And from a dataset standpoint, it's the only oral that had a hit on confirmed disability reduction in both Phase III trials, prevention of progression there. So it has a strong dataset. ICER evaluated the class and concluded that the platform therapies and the orals did not meet cost-effective criteria. But I think this was a good example where we're still in dialogue with them. I think we'd have some concerns about the numbers that they actually used to do that calculation and perhaps not recognizing the full value of Aubagio. And Aubagio, just again to remind you, it's 9% market share in the U.S., fastest-growing oral and 11% in new scripts. So I think the Aubagio picture still remains extremely strong. And conversely, on the pricing standpoint in the ICER evaluation, Lemtrada was the one product in the MS class which was judged cost-effective and by a very large margin. So that's it.

All right. Thank you, David. And Vincent, for your last question, so you heard Jérôme. So we have bought back share at the value of €2.8 billion, €2.9 billion since we announced the share buyback program. That included what we did in Q4 last year to the tune of €1.5 billion and a further €1.3 billion, €1.4 billion as of mid-April. It's actually €1.4 billion. Now to your specific question, I think we can keep in mind that we can always look at opportunistic purchases once we have reached €3.5 billion figure. However, when it comes to the priority of allocation, M&A remains above the share buyback allocation. And you expressed a potential case where we would find anything. But again, we're, as you would expect, looking into different TAs I was mentioning before. And that can eventually happen. So that's what I would answer. That's what I would respond.

The next question comes from the line of Mr. Richard Vosser of JPMorgan.

Just a follow-up on Soliqua, please, just you mentioned the formulary access last quarter and kicking in from July. So just perhaps if you could give us an update on how that access discussion is going at the moment, please? And then secondly, just on the Dupixent data mentioned in the press release from the CAFÉ trial, could you just clarify the meaning of the acceptable safety profile? Have you seen a different safety profile in this trial compared to the previous Phase III trials which has obviously been very good. Just some clarity there would be very useful.

Okay. Thank you, Richard. Soliqua access, yes, Peter?

So Soliqua access, what we've seen is that some payers tried to look at the 2 products, so Soliqua and Xultophy, together. So they are kind of delaying their decision in terms of access. This being said, with what we know today, we know that we have 34% commercial access and 31% R&D access already signed but not necessarily all in place. Some of that is yet to come into effect. And actually, during the first quarter, there was actually no access with the exception of the last 2 weeks of the first quarter. So what you see actually in net sales, of course, was Soliqua is underestimated because of the couponing part, the $0 co-pay which of course, offsets against net sales. Perhaps one additional word on Soliqua, it's obviously very early days. We're only a couple of weeks out of the gate. But it's clear that in terms of patient identification, you know that the product has in its label the intensification space, right, so either patients not [indiscernible] with basal insulin alone, so patients where you would either up-titrate with your basal insulin or intensify them, for example, by adding a GLP-1 or a prandial insulin. So that is actually the sweet spot for Soliqua. But that requires a bit of education of our physicians. So that's really what we're focusing on as we speak. And we see that after a certain number of visits, they got that message. So what I'm trying to say is that, of course, the access which is gradual and the education of our customer bases will require some time. And therefore, you will see a gradual uptake of Soliqua.

So for the CAFÉ safety profile, we did not observe any significant difference in the safety profile in CAFÉ as the others. So nothing to report there.

Nothing to report, okay.

The next question comes from the line of Jeffrey Holford of Jefferies.

Wonder if you'd like to just comment around the strategy for consumer regarding M&A, whether you have appetite to do business development there immediately or whether you'll need to sort of see through 2017 before you're ready to integrate more transactions. And then actually just would like to step back a moment, just talk more broadly about your Oncology strategy, whether there are specific areas you feel you want to intensify in terms of product additions and development and whether there are specific areas, like hematology or solid tumors in particular, you feel is more attractive for you to focus on.

All right. So on the CHC strategies, definitely we're busy integrating this relatively large business portfolio from BI. We're going that well and Alan is managing his team very effectively. And you can see already that through the results we're posting for this quarter that it's working well. Does that mean that in the midterm or longer term, we wouldn't look at eventually strengthening even further this business? Of course not. So we would be open. As I said, CHC is part of the TAs and areas we wanted to strengthen. We have done definitely a very important step there. But it might not be the end of the story and opportunities will be critical or will determine the future of that aspect. So that's for CHC. Do you want to answer the question on Oncology, Elias?

Sure. Yes, let me first state that the Oncology strategy is a multi-tier strategy, multiphase. First and foremost, we're going to continue to develop the franchise around CD38. And when you asked the question, as you know, CD38 is for myeloma. But science shows that it has other potential indications, such as in other hematological malignancies and we're going to explore that as well as combined with PD-1 in which we're already starting some early work, it is actually possible to see indications in tumors, in solid tumors. And the reason is that science is showing that CD38 seems to be in itself a checkpoint inhibitor. And this is what the -- is driving, if you will, the growth of this very important pillar. In addition, we will continue our own internal programs in antibody drug conjugates. We're in talk stage for those. Second, we're going to build the immuno-oncology franchise on 2 axes. One, obviously, is the collaboration with Regeneron which gives us the checkpoint inhibitors we need, PD-1 and LAG3. And then combined with our own internal assets which are immune activators, if you will, our TGF-beta antibody, our neukine and other approaches that we're putting together which will complement, if you will, the effort with Regeneron. Third, we believe that there is an opportunity in Oncology to perhaps acquire some assets that will be complementary to our portfolio. So we're looking at opportunities that will be complementary strategically to our prostate portfolio, for example and our breast cancer portfolio. We have both internal and external programs that we're looking at for that purpose. So that's the approach. We're building on what we have. We're continuing to build on a complementary strategy to that of the Regeneron, Sanofi collaboration. We will build the part of it that is immune activating. And on top of that, we'll build the multi-targeting strategies that seem to become the dominant approach in cancer control.

Do you want to add a word on the ADC platform we have?

Right. So the antibody drug conjugate platform is in the clinic right now. We have 3 of them. And we have early promising clinical data that will be expanded further. And clearly, those are assets that we will continue to explore.

Next question comes from the line of Luisa Hector of Exane BNP Paribas.

On Dupixent, can you confirm whether the CAFÉ results are actually required to get the European approval by the end of the year? And then on Diabetes, the glargine franchise, I'm just wondering that now we're sort of seeing more developments in the competitive landscape with BASAGLAR, Soliqua, Xultophy, whether there's any change to your target market share that the Toujeo switch can achieve and whether perhaps Soliqua -- you have a bit more confidence in Soliqua perhaps taking more share than you expected now that we have more information on all the dynamics there.

All right. Thank you, Luisa. Elias, maybe you should answer the regulatory question around CAFÉ.

Yes, CAFÉ was, in fact, a requirement of the EMA. In Europe, they do want you to conduct trials against established standard of care, in this case, even nonestablished standard of care [indiscernible] cyclosporine. So it was a requirement of EMA, yes.

Luisa, your question on Toujeo and, let's say, insulins in general with the increased competition in the field of Diabetes. We stick to our initial thinking. So we think that Toujeo is sufficiently differentiated to make the mark. We're happy with the initial launch of this product. It continues to perform extremely well in Europe. We take very significant market shares. We're coming back to very good performances in Japan. We have been making our first launches in Emerging Markets, where the expectation of the product is also a very good. And the interesting thing is that despite all the new competition in the field of Diabetes in general is that the overall insulin market in volumes, even in the U.S., continues to grow 3%, 4%, 5% depending on the quarter. So that's number one. Number two, in countries where we have more maturity with Toujeo, you take, for example, Germany which was the first launch country in Europe, you see, of course, in the beginning that the first source of business for Toujeo is switches from basal insulin and, of course, to the large extent, Lantus. But you see also that moving forward, that Toujeo captures more and more new patients. For example, today in Germany, the source of business is already 2/3 new patients, right which of course, is an interesting, let's say, opportunity for us to take if you take -- if you look at the overall glargine franchise of Sanofi. So number two on Soliqua, again I provided some early insights, too, in the previous question. Again, it's early days. Don't forget that in the U.S., so FDA did not give us the first injectable label, so post-OAD label, whereas in Europe, we have both the post-OAD label and the insulin intensification label. So that is a fundamental difference of appreciation between EMA and FDA because, of course, the file obviously was the same. So that is basically what I can tell you.

Next question comes from the line of Philippe Lanone of Natixis.

Two remaining ones. First, on CHC, we have a strong growth. However, 40% of that is Xyzal launch. And if we strip out also the strong flu season, probably the underlying growth still is a bit weak. Or is it? And how do you -- can we see that going forward? And can you comment on how the BI business is doing and whether you still maintain the target of bringing the margins of BI to the former Sanofi has won in this business? And another question on Lemtrada which is doing pretty well and accelerating this quarter, while some of the competitors have signaled some weakness in Multiple Sclerosis market on the wake of OCREVU.S. launch by Roche, it should be, I mean, the main target commercially for OCREVU.S.. How do you see this product going forward with this competition?

All right. Thank you for your good questions. So CHC, Alan?

Obviously, you highlighted some of the main impacts of the Q1 performance overall. The pipeline effect of Xyzal, the new switch allergy product in the U.S. So that was just getting in its pipeline fill into the retail sector at the end of the first quarter. It's obviously a bit too early to indicate there, although the first signs of allergy season in the U.S. are relatively weak. But we're not near the peak season yet which comes in the next 2 or 3 weeks. Cough and cold was strong, but it was strong early. We saw bigger pathology in Europe in November, December. And that carried on through into January, so slightly early season this year compared to previous years. And of course, with the addition of the BI portfolio, we're strong in cough and cold in Europe. So we obviously took advantage of that overall positive pathology. The underlying business, I think, is a strong. And to your comment on the BI franchise, we saw no business disruption in the first couple of months of operation. Everything is going well. We're also on track to deliver the synergy targets as indicated and that will go a long way to raising the margin, as you rightly said, towards the Sanofi standard. As overall, I think everything on track, underlying business looking positive and some seasonality obviously we have to build in but overall on track.

All right. Thank you, Alan. David, Lemtrada?

Yes, so thanks for the question on Lemtrada. I think, obviously there's a lot of discussion around ocrelizumab, TYSABRI and Lemtrada all falling in what they call the high-efficacy class. I think the impact on Lemtrada is going to be less, to be honest with you, for the following reason. I think there'll be no impact. But Lemtrada is a unique mechanism of action here which is that, I'll remind you, it depletes -- targets anti-CD52, it depletes the white blood cells, T cells and B cells and they come back. And then we believe the mechanism of action is in the repopulation of those white blood cells. The MS is reset so that autoimmune response is no longer seeing MS in quite the same way. And the data for that is we're now at 6 years. So 5 years after your last treatment, we know that 55% to 60-plus percent of the patients from our Phase III trials we've been following long term have not required any additional therapy. So in essence, they have stable MS without any need for further therapy. That's a very different mechanism of action than what is in place with TYSABRI and with ocrelizumab, where you get chronic immunosuppression. So I think there's a lot of questions still. Again, it's an early therapy. Data is limited when drugs are first launched. We've got 13,500 patients on Lemtrada to date with 8,000 plus, years of follow-up and the like. I think we're going to do fine there. In fact, one hope would be that the presence of ocrelizumab actually drives growth in the high-efficacy class as a whole which is right now only around 10%. So the pipe could go larger, the share of each drug may shift. But overall, the opportunity may be greater.

The next question comes from the line of Jack Scannell of UBS.

A couple of questions. First, fitusiran in hemophilia, a couple of things. First, could you just give us an indication as to what gave you confidence that we may not see -- we won't see some of the safety problems with this agent that we've seen in some other novel hemophilia agents? And secondly, do you think the sweet spot is likely to lie in hemophilia A or hemophilia B? And the second question relates to kind of the impact of out-of-pocket costs. It seems that Americans are increasing, I suppose, their out-of-pocket costs, particularly Medicare Part D population and that influences behavior. [indiscernible] patient or Medicare Part D, roughly what would be their incremental monthly out-of-pocket cost?

All right, Jack. Fitusiran question.

So we carefully looked at all the data on fitusiran. And frankly, if you look at the #1 safety event for fitusiran, if you remember the mechanism is to reduce the amount of antithrombin, therefore, maintain the thrombus. Then the risk obviously will be thrombogenic risk. We have seen none of that. And because we didn't see any thrombogenic risk and we saw a significant reduction in the antithrombin levels, we felt that it was the right thing to do to continue the trial into Phase III. Obviously, we're monitoring all these patients. So far, we haven't seen any thrombotic risks. So it gives us also the confidence that it will be a very novel therapy because it can truly change the paradigm in many ways, especially in patients who have inhibitors, where other approaches are not working and you can essentially treat these patients with a subcutaneous injection and maintain their status for a time that is still to be determined, a month, 2, 3. So that's why we continued the trial of fitusiran.

All right. Then [indiscernible] of Praluent.

So Praluent or in this case, PCSK9 in general in Medicare Part D, of course, is an issue because with the exception of the low-income subsidy patients which account for about 20% of the total Medicare population, so the remaining 80% has, of course, coinsurance for those products. And to give you an idea for the PCSK9 class, it means that the out-of-pocket payment would be above $3,000 a year, even higher in some cases which is, of course, pretty prohibitive for most of those patients. And we see indeed that there is a huge dropoff, not to say -- well and possibility of even starting the treatment for many of those patients, given the high out-of-pocket for Praluent.

The next question comes from the line of Jo Walton of Credit Suisse.

Just two remaining questions, please. You have highlighted fantastic performance with your couponing, retaining 43% of share in part of the CVS formulary. Does that antagonize CVS and make it more difficult when you come to negotiate next year? Because their whole rationale is that they can control volumes and this couponing is going against that. So I just wonder if you could tell us a little bit about how you're seeing them fight back? And do you think that United are a better organization at instilling their formulary? Or do you think that we should be able to see you with your couponing retain a significant proportion of United business going forward? And my second question, just result looks at the Established Products. If I look at your European business and your Emerging Markets business, you had a stronger performance in the first quarter with both of these than you have historically had over the last few years. Was there anything or is there anything unusual about the first quarter? Or have we managed to annualize out some of the high declines? And could this be a new level of growth for that established or low declines for that established business?

Okay. Good questions, Jo. So let's go to Diabetes first, couponing in the 43% and 55%.

Thanks for the compliment. It's a lot of good. But of course, whether this antagonizes CVS, as you mentioned, I don't know. I think you should probably refer that question to them. Your question on United, look, I think that it's very hard to predict how this will play out. We, of course, have 3 months more experience now, where we're going to the United part. And again, our objective is to make sure that we have as less a disruption as possible for the patients. So we're just trying to put patients first here with this action. And that's what really matters for us. So I think the other part of your question, I'm afraid I can't really answer.

But the impact on United because the base is different would not be as great as on CVS, right?

Yes. No, I'm more referring to the relative retention we can keep in United with the couponing. So we'll see. But what I'm trying to express is that we have 3 months more experience now that we have, so to speak, exercised for 3 months with CVS. So there's reason to believe that we will be reasonably affected for United. And of course, in parallel, Jo, we work our way through access for Soliqua, of course. And you know that this is the most strategic objective.

All right, thank you. Thank you, Peter. So Olivier, established in emerging and developed countries?

So of course, thank you for your question, Jo. So in the mature markets, of course, we're less impacted by the generic competition to Plavix in Japan. And we used quarter-on quarter, year-on-year to lose 40% to 50% in the last quarters. For this quarter, we lose only 30%. Our overall performance for Established Products in mature markets is going to be impacted in the coming months, depending on the entry of potential generic novologs in Europe and in the U.S. for [indiscernible]. Regarding the Emerging Markets, we had a strong performance on our Established Products portfolio, driven by all continents. We have double-digit growth across all continents with a specific note to Brazil and China, very strong performance in China. In China, it's Plavix that continues to grow very nicely as well as the rest of our portfolio, including Lovenox. So strong quarter in the Emerging Markets, reflecting a strong performance in China and in Brazil. But for the mature markets, good performance for the quarter, but we will continue to be impacted by potential entry of generics in the upcoming quarters.

All right. Thank you very much, Olivier. So that's the end of the call.

Thank you all for dialing in for today's call. Of course, the IR team will be around for the rest of the day to answer as many questions you might have. So that will conclude today's call.

Very good. Thank you very much, everyone.

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