Good afternoon, and thank you for joining us today. I am Pascal Soriot, and I am joined by Marc Dunoyer, our Chief Financial Officer, and Briggs Morrison, our Chief Medical Officer and EVP of Global Medicines Development. For the Q&A part at the end of the presentation, we will also have Luke Miels, our EVP of Global Portfolio and Product Strategy with us, as well as Ed Bradley, SVP of MedImmune Oncology, on the telephone with us today. We will spend a short time updating you on the first nine months and the progress we have made in achieving scientific leadership and returning to growth. I will start by providing a brief overview of the key highlights. I will then hand over to Marc for an update on our growth platforms and more detail on the financial performance and guidance for 2014. In addition, Marc will give a preview for 2015.
Briggs will briefly discuss our R&D pipeline progress for the quarter and the expected news flow until our next quarterly conference call. I will come back before opening the call for your questions. We have posted a set of slides on the investor page of our website that will follow along with this presentation. We will try to cue the slide numbers as we go through. Starting with our results for the first nine months, I am very pleased to note that this is our third consecutive quarter of revenue growth. We had sales of over $6.5 billion in the quarter, which was up 5% at CER. During the first nine months, more than 50% of revenue originated from our growth platforms, which were up 16% year-to-date. As Marc will discuss in more detail, we have increased revenue and Core EPS guidance for the full year.
This is the second upgrade to our guidance in 2014. BRILINTA is showing good momentum across all regions, with sales up 78%. The highlights for our diabetes franchise are the successful launch of FARXIGA in the U.S., as well as strong uptake of the BYDUREON pen, which we launched in the third quarter. Our respiratory business has had a good first nine months, and we have seen continued strong growth for SYMBICORT in the U.S. I would also like to highlight the third consecutive quarter of double-digit growth in the emerging markets. In particular, we have seen 22% growth in China, where we continue to outpace the market. Sales in Japan were stable in the first nine months due to price cuts and other market conditions, which we will discuss later in more detail. We have also made significant progress toward achieving scientific leadership in our core therapeutic areas.
FDA approved XIGDUO XR, which is the first fixed-dose combination of a once-daily SGLT2 inhibitor and metformin. We received a positive opinion by the CHMP for LYNPARZA, or olaparib, our ovarian cancer treatment for patients with a BRCA mutation. We look forward to receiving European Commission approval in the coming months. We also have the U.S. PDUFA date on third of January 2015. For IRESSA, we received a label update in Europe to include blood-based testing for the activating mutation, which renders patients eligible for IRESSA treatment. In addition, the FDA approved MOVANTIK. We believe this medicine has real benefits for patients, and we look forward to launching it at the end of Q1 2015, early Q2, after we have received the descheduling. Further, the EMA has adopted a positive opinion on MOVANTIK for opioid-induced constipation.
We've had phase III data readouts for our gout therapy, lesinurad, and for ceftazidime-avibactam, a treatment for intra-abdominal infections. Finally, we've seen significant business development activity supporting our strategic priorities. Turning to slide six, we see positive revenue growth for the first nine months, up 4% at CER. Importantly, more than half of revenue, which equates to over $10 billion, was driven by our growth platforms, which have shown a strong good growth of 16% in the first nine months. Going by region, in the U.S., revenue is up 6% year-to-date. This growth was driven by SYMBICORT, BRILINTA, and diabetes. In Europe, the favorable growth of BRILINTA and the diabetes brands were offset by the continuing impact of loss of exclusivity on Seroquel XR and price pressure on Crestor and SYMBICORT.
Emerging markets was up 12%, with growth in China well ahead of the market at 22%, which Marc will walk you through in more detail. In Japan, sales were stable, impacted by the price cuts and the increased use of generics, in particular in oncology. Core EPS for the group was down 3% at CER for the first nine months as we continued to selectively invest in our growth platforms and expanding pipeline. As Marc will go on to discuss, we've upgraded our full-year Core EPS guidance. Slide seven is simply a reminder of our three strategic priorities. I believe we're making good progress on all of those priorities. On slide eight, we're looking in more detail at our five growth drivers. As I said before, they contributed over half of our revenue during the first nine months.
On the right-hand side of the slide, you can see the relative contribution from each of these. It's worth noting that without the additional revenue from the acquisition of the BMS share of the AstraZeneca/Bristol-Myers Squibb Diabetes Alliance, our diabetes franchise still grew by 26%. I will now hand over to Marc, who will take you through each of the growth platforms in more detail and provide an overview of AstraZeneca's financial performance for the first nine months. Marc, over to you.
Thank you, Pascal, and good afternoon, everyone. Let me start with BRILINTA on slide 10. Sales were $127 million in the third quarter, up 68% at CER, with strong performance across regions. We saw continued good momentum in the United States, supported by the positive news of the U.S. Department of Justice closing its investigation. The U.S. was the fastest-growing region in the third quarter. Europe remains strong, with third-quarter sales up 36%. The next big milestone for BRILINTA will be the PEGASUS top-line results, which we're expecting early next year. As you can see on the left-hand side of slide 11, BRILINTA is now the branded oral antiplatelet leader in U.S. hospital purchases. This has been helped by the new preferred status for BRILINTA on the updated American Heart Association/American College of Cardiology guidelines for non-ST elevation ACS patients.
On the right-hand side of slide 11, we can see how we steadily continue to take market share in the U.S., and the new to brand market share is now 7.5%. We have always believed in the potential of these products and are pleased with the steady progress it continues to make with ongoing investment. Let's now move to diabetes on slide 12. We have seen strong performance over the quarter, driven primarily by the launch of the new BYDUREON pen device in the U.S. and the good FARXIGA uptake also in the U.S. For ONGLYZA, however, we have seen a small TRx share decline, although volumes have been stable in a growing market. On slide 13, on the left, you can see that the FARXIGA volume trends continue to grow steadily.
On the right-hand side of the slide, we show the effect of the FARXIGA launch on the monthly new prescription volume in the SGLT2 class. As you can see, the volume growth for FARXIGA is not coming at the expense of other SGLT2 inhibitors. Instead, we see an acceleration of the overall class post-FARXIGA launch. Slide 14 shows on the left the reversal of the slowing rate of growth for the GLP-1 class. During the last two quarters, we have seen an acceleration of the TRx volume growth. On the right, you see how BYDUREON volumes continues to grow, and following the launch of the new pen device, the early signs indicate additional volume growth.
Looking at slide 15, you can see the impact of our new BYDUREON pen device, which it had on the prescription market share in the GLP-1 class on the left, and in our TRx volume on the right-hand side. By now, more than a third of BYDUREON prescription are with the pen, and this has led to a trend break in TRx volume increase for the total BYDUREON family. Now moving to our respiratory franchise on slide 16, you see continued strong growth of SYMBICORT. Its sales up 15% in the quarter. SYMBICORT performance was particularly strong in the U.S., with sales up 29% in the quarter. It should be noted that our realized net price for U.S. SYMBICORT has been stable in the third quarter and year-to-date. Sales in Europe were down 1%, as price pressure was offsetting a 6% volume growth.
Looking more closely at SYMBICORT performance in the U.S. on page 17, we can see new to combination therapy market share at 37.5% in the U.S., which is a 3.6 share point increase since the end of last year. We estimate that around 40% of these market share gains are attributable to the ESI formulary win, which kicked in at the beginning of 2014. Therefore, our gain this year will be a tougher comparison going into 2015. I've already mentioned our strong double-digit growth in emerging markets for the third consecutive quarter. If you look at slide 18, you can see our growth in China compares to the rest of the industry, with our growth shown in purple outperforming the rest of the market. I'm also pleased to say that our emerging market business is doing well outside China.
In the third quarter, our ex-China emerging market business grew by 9%. Moving on to slide 19. In Japan, we see positive underlying demand for primary care launch brands in Japan, Crestor, SYMBICORT, and Nexium, continue to post strong volume growth as you can see on the left-hand side of the slide. Despite a healthy mid-single digit in market growth in Japan, the performance has been impacted by the biannual price cuts and increased use of generics. Turning to slide 20, total revenue for the third quarter grew by 5% at constant exchange rate to $6.5 billion, our third consecutive quarter of revenue growth. The currency impact on third-quarter revenues was negligible. Core EPS for the quarter was $1.05, a decrease of 8% at CER. The impact of foreign exchange lowered core EPS by five percentage points at actual rates.
On slide 21, I will now turn to the P&L for the first nine months. I will focus on core margin and profit. The press release contains the statutory numbers and a detailed reconciliation to the core measures. As a reminder, when I refer to growth rates, they will all be at constant exchange rates. Revenue was up 4%. Core gross margin was 81.8% of revenue. Core R&D expense in the first nine months was up 14%, reflecting our conscious investment in a rapidly growing late-stage pipeline. Expenditures in core SG&A were 14% higher than the first nine months of last year. The increase in spend was dedicated to the growth platform and supported the sales growth for three core franchises, Respiratory, Diabetes, and BRILINTA of 31%. Part of the increase relate to the inclusion of 100% of the cost associated with the Diabetes portfolio.
Growth in core SG&A expenses also include the change to reporting around the U.S. branded prescription drug fee, which will now account for current year fees versus previous year fees in past quarters. As we expect 2014 fees to be higher than 2013 fees, which we have accrued for so far, we have made a small addition in quarter three, which goes through core SG&A. Core other income in the first nine months was 69%, with milestone-related income related to the launch of Nexium OTC being the largest driver. Core operating profit in the first nine months was down 6% to $5.8 billion. Core operating margin was 29.6% of revenue. Finally, net cash from operation was $5.2 billion, thanks to the improvement in working capital despite a lower operating profit. As you have seen during this week, we have signed and completed several new business development deals.
As shown on slide 22, all these deals support our three core therapeutic areas. The divestment of Myalept, metreleptin, to Aegerion Pharmaceuticals allows us to redeploy resources in our core priorities while ensuring access of patients suffering from this rare disease. In the oncology field, the deal with Pharmacyclics and Janssen enable us to investigate novel immune oncology and small molecule combination in hematological and solid cancers. The acquisition of Definiens gives us access to novel predictive biomarkers, which we think can be important for immune oncology efforts. Earlier this week, we have also announced the closure of the respiratory deal with Almirall. It's a pleasure for us to welcome the highly regarded team from Almirall who will strengthen our respiratory franchise. Let me now turn to guidance for 2014 on slide 23.
We now expect revenue for 2014 to increase in low single digit at CER, which is an upgrade from our guidance at second quarter results. In light of the overall increase in revenue expectation for the year, we are accelerating our investments in our growth platforms and expanding pipeline. Therefore, Core EPS is expected to decrease at around 10% for 2014, better than anticipated in previous guidance. You should keep in mind that Core EPS for 2014 at actual exchange rate is expected to be impacted negatively by currency by an additional 5%, assuming current exchange rates. This guidance assume no U.S. Nexium generic in 2014. I would also like to point out the new guidelines by the American Academy of Pediatrics, which we expect to significantly impact Synagis sales negatively in the first quarter of 2014 and into 2015.
Finally, on slide 24, I would like to give you a preview of how we look at 2015. Our plan for 2015 is to continue to selectively invest in our growth platforms and accelerating pipeline while managing overall cost. Assuming current exchange rates, the company is targeting Core EPS for 2015 to be no less than the lower end of the range of the upgraded guidance for Core EPS for 2014 at actual exchange rates. Guidance for 2015 is expected to be provided with the 2014 results on February 5th, 2015. With that, I will now hand over to Briggs.
Thank you very much, Marc. On slide 26, I think slide 26 is a great example of the continued momentum we've seen in our late-stage pipeline. On the regulatory side, we've recently received a positive opinion from the CHMP in Europe for olaparib in platinum-sensitive relapsed BRCA-mutated ovarian cancer. For IRESSA, we have managed to obtain a label update, which includes blood-based testing for EGFR mutations to help identify patients likely to respond to the drug. In the U.S., XIGDUO XR has been approved. This is the first once-daily SGLT2 metformin fixed-dose combination. Last but not least, MOVANTIK was approved by the FDA for opioid-induced constipation and received a positive opinion from the CHMP.
As Pascal noted, you will recall that the rate-limiting step for the launch of MOVANTIK in the U.S. is the descheduling by the DEA, which we now anticipate in the first or second quarter, early second quarter of next year. During the last quarter, we've also had phase III data readouts from lesinurad as an add-on treatment in gout and for ceftazidime-avibactam in complicated intra-abdominal infections. In addition, we've presented what we believe are compelling results at both ESMO and at ESC. The next major scientific meeting for AstraZeneca will be the American College of Rheumatology meeting, which is starting next week in Boston. On slide 27, you can see the key data that will be presented at ACR for our developmental drugs in lupus, rheumatoid arthritis, and gout. In the near term, we anticipate continued strong news flow for several of our late-stage pipeline assets.
All the data readouts and regulatory milestones are summarized on slide 28. Perhaps most notably, we're looking forward to the data from the two remaining brodalumab phase III studies in psoriasis. This is a collaboration we have together with Amgen. That data should read out before the end of the calendar year. On the lower part of slide 28, you can see a summary of near-term regulatory milestones we anticipate during 2014 and early 2015. More details on our pipeline transformation will be provided at our upcoming Investors Day. I'll turn it back to Pascal.
Thank you, Briggs. In closing, I'm really pleased with the progress we're making on our growth platforms and our pipeline. The growth platforms grew by 16% and contributed to over half of our revenue during the first nine months. We continue to selectively invest and support our growth platforms and our expanding pipeline. Despite this, we have managed to upgrade our revenue and our Core EPS guidance for 2014. We confirm our progressive dividend policy moving forward. Lastly, we have provided a preview for our Core EPS in 2015. Thank you for your time today. I hope to see many of you at the Investors Day later this month, where we'll be providing further detail on the execution of our strategy. I hope you understand that we may not address all the aspects of our pipeline today.
We want to spend more time on this at the Investors Day. With that, I would like to now open for questions. Over to you, operator. We have a question from Alexandra Hauber at UBS. Alexandra, do you want to go ahead?
Yes, good afternoon. Three questions, please. Firstly, since we know that we shouldn't ask about the pipeline. On SYMBICORT, you're having very strong growth momentum, in particular in volume terms in the U.S. Given that you're excluded from the CVS Caremark formularies next year, which is about, my understanding, 20% of lives, would it be correct to assume just looking at the current volume growth and what Caremark is, that we should still see decent volume growth next year in SYMBICORT? Can you tell us whether pricing next year will be a positive or a negative effect for SYMBICORT? Secondly, a lot of things have been going on at AstraZeneca this year, so forgive me for asking for something that hasn't happened yet. That is, we haven't seen an Epanova launch, despite the approval for a long time.
Is that something which you may deprioritize and potentially decide that it will face a similar face as metreleptin? The third question is, can you tell us what is so proprietary about the Definiens technology that you actually needed to own it rather than just license their technology?
Okay. Should I Alexandra, do you want to try again? Go ahead.
Hello? Hello?
Go ahead, Alexandra. Sorry, we had a problem here, a technical problem. We can hear you now. Go ahead.
Okay. Sorry. I start again from the beginning?
Yes, please. Yeah.
I have three questions. The first one was on SYMBICORT. You're having very strong volume growth at the moment, but that we expect to slow given that you will be excluded next year from the CVS Caremark formulary. However, that's only about 20% of lives, I understand, and your volume growth is currently exceeding that. Would it be correct to be relatively confident that there's still volume growth with SYMBICORT? Would you be prepared to tell us whether you think pricing is going to be positive or negative in 2015? The second question was on something that hasn't happened yet. I'm aware a lot of things have happened at AstraZeneca this year, and that is actually an Epanova launch.
It was approved about six months ago. Are you still committed to launch it at all, or maybe see something similar as what we've seen today from metreleptin? The third question is, what is so proprietary about the Definiens technology that you felt you had to own it rather than just license it?
Thank you, Alexandra. We have Ed on the phone and I'll ask Ed to cover the Definiens question. Let me start with SYMBICORT. Just high level, we should expect price pressure on SYMBICORT next year and some volume goals, maybe Luke, do you want to cover this in more details on SYMBICORT U.S.?
Alexandra, thanks for your question. I think the growth that we're seeing this year should not be extrapolated into 2015. I think it reflects access and commercial success. Next year, we do expect lower growth, much lower growth based on a mixture of access changes and pricing pressure.
Net-net is you will see some growth, but certainly as you could expect, lower than this year, Alexandra, because the market is changing. As far as Epanova, we are still committed. We had to address some supply manufacturing and supply issues, and we prioritized the supply to our STRENGTH study, which has now started and has started enrolling patients. Our priority was to supply the study, number one. Number two, for the time being, we want to focus all our efforts on growing our diabetes franchise, still defending Crestor and then growing BRILINTA. Of course, the sales force that will be promoting Epanova is the sales force that is today engaged in our diabetes franchise. It's more a question of priorities. First of all, supply going to the study, and then secondly, the priorities around our sales force.
We are still committed, and you'll hear back from us at some point as far as Epanova. Definiens, Ed, if you are online, do you want to cover this question?
Sure. Thank you, Pascal. Definiens is a very powerful and proprietary integrated platform for core tissue genomics. It does two things. It has very sensitive tissue imaging, which enables us to look at multiple markers to identify all of the immunocytes immune responsive cells in a patient's tumor. It also enables us to see exactly what the relationship is to the tumor cells and whether they're killing them or not. It uses very powerful computerized algorithms to make millions of correlations in any individual patient to see exactly what cells are responsible for killing tumor cells. This is applied in clinical trials, and it enables us not only to identify future biomarkers that might be useful, but also enables us to make rapid decisions in the ongoing development of clinical drugs, and particularly in combinations that we need to explore.
Thank you, Ed. What about next question is from James Gordon at JPMorgan.
Hello, thanks for taking my questions. This is James Gordon from JPMorgan. I had a couple of questions on Nexium and the U.S. generic situation. My question was, I've seen that Ranbaxy put out a statement stating that their tentative Nexium ANDA approval has been rescinded. It doesn't say whether they forfeited their eligibility for 180 days exclusivity. A couple of questions on that. One was, what's your understanding about if the Ranbaxy 180 days is rescinded, does that mean immediately that multiple generic companies could come to the market with a generic Nexium? Also just how do you think it works in terms of does anyone else then get 180 days, or is it a complete free-for-all?
Yeah.
Question. On the partnership I saw where you're partnering your PD-L1 in combo with ibrutinib, have you already seen any encouraging data for PD-L1 in hematological cancers? Assuming you have, when could we see some data on that?
Okay, James, thank you. On PD-L1, I'll ask Ed as well to cover this question. Starting with your Nexium question, I have to say it's a great question, and to be totally candid with you, we are not totally sure how to read this Ranbaxy announcement. I think we'll just have to wait and see how these discussions with the FDA develop and what that means as far as Ranbaxy and potentially other generics being launched. Maybe a couple of things I could say is one is our assumption remains that there will not be any Nexium generic being launched this year. The second point is, so far, there's no other generic that has been approved. To keep this in mind.
As far as Ranbaxy themselves, again, to be totally candid, we don't exactly know how to read this announcement, and we'll just have to wait to learn more about it. Ed, do you want to cover the PD-L1 question?
Sure. Thank you. Yes, there's a lot of preclinical data that supports the activity of the PD pathway in hematologic malignancies. We have trials that are ongoing. It's too early to discuss any data from those, but we're enthusiastic about that and also about the combination with ibrutinib.
Thank you, Ed. Tim Anderson at Sanford Bernstein. Tim, do you want to go ahead?
Yes. Thank you very much. A question, kind of like the one you got on SYMBICORT, really on the diabetes franchise. I'm wondering if you can talk about kind of pricing and market access, especially in the U.S. with your diabetes products, whether that's ONGLYZA and BYDUREON or FARXIGA, given the fact that we've seen price compression in diabetes. On ONGLYZA specifically, can you update us on the possibility of where you are with the FDA and the heart failure risk? Do you think FDA is waiting for the TECOS trial with Merck before they make any decisions? Last question on 2015, the soft guidance on earnings. Can you speak to the tax rate side of that? For the last two quarters this year, your tax rate has been lower than consensus as expected.
Okay. Thanks very much, Tim. I'll ask Marc to cover the tax questions. Just a quick comment. We've had a number of one-off events this year that you should
Safety is comparable to placebo we saw in SAVOR. There was a difference in hospitalization for heart failure, not in total congestive heart failure. Obviously, we've submitted that data to regulatory agencies. We'll have to wait and see what comes out of the Merck TECOS trial. At this point, we have not had any significant concerns from regulators.
Thanks, Briggs. As far as the other question on diabetes, I'll ask Luke to add anything if he wants. Maybe the general comment I would make here is that, whether it's in diabetes field or respiratory field, we expect certainly increased competition. Some products will be impacted by price pressure more than others. We don't really want to comment on one product to another. Maybe the one thing I could tell you is that, for 2015, across the entire portfolio of products, across our entire business, if you want, in the U.S., our assumption is we will see a negative price impact in the low single digit. That's across the entire portfolio. We're not going to comment on product by product, as you can imagine, for commercial reasons. Luke, anything you want to add?
I would just make an overall comment. I think we have a competitive portfolio. We have XIGDUO, of course, with, we think, an attractive label. We have the dual-chamber pen, of course, and in the medium term, compounds like saxagliptin.
By the way, just to add, our 2015 preview assumes this increased price pressures across the pipeline. Not the pipeline, sorry, the portfolio. We've built in the low single-digit price reduction across the portfolio that I've just mentioned a minute ago. Moving on to the tax question.
Yes.
Thank you for the question. I think we will be in better place next year in February to provide more details about our assumed tax rate for 2015. Where we see it today shouldn't be dramatically different from where we were last year or this year. It should be in the same region. We would like to provide you with more detailed information when we meet with you in February. Okay, thank you, Marc. Sachin Jain at Bank of America. Sachin, do you want to go ahead?
Hi, thanks for taking my questions. Three, please. Firstly, on cost base progression. Two aspects. Firstly, can you just give some color on what you're expecting for fourth quarter, given the 2014 guidance basically implies a fourth quarter earnings down 20%-25% sequentially on 3Q without generic Nexium. Any color on that? Then any color on cost base into 2015, and what flexibility you have around potential Nexium U.S. generic timing. Second question is on balance sheet intention, given comments from the media call that left deals are needed given pipeline progression. As you move towards a net cash position some point next year, what's your intention for balance sheet? Then the third question for Ed on IO, just a very broad question.
What data should we expect from the portfolio of assets by year-end, given multiple potential for offer data being ASH, San Antonio, and the Analyst Day? Thank you.
Thanks, Sachin. Ed will cover this question in a minute or two. Maybe I could start with the cost base and ask Marc to add on that and also cover the balance sheet question. The cost base, as we said, we will continue this year to invest in our growth platforms. In fact, this year, you should see 2014 as really an investment. Almost a launch year. A year in which we are launching several products. I would call the emerging markets a product if you want. Essentially, we are launching quite a number of diabetes products. We are still relaunching BRILINTA, and the good news is we are starting to see momentum there, including in the U.S. We are sort of relaunching still SYMBICORT with great results. Finally, we are launching China. In fact, the investment in China this year has been very substantial. We've increased the size of the sales force very substantially, and the result is what you see. A growth rate that is very, very substantially above the market growth rate. That is to be considered a launch year.
Next year, we move to a different phase, where we still have launches. Of course, we have olaparib, but it's in oncology. It's much less costly. We get to a more stable phase of our business. Next year, you should assume we still invest in our pipeline, but certainly, we will start managing SG&A costs and improving productivity and certainly looking for synergies across the entire sales force and managing that cost base. That's why we feel comfortable delivering or giving you today this preview as far as 2015 Core EPS. Nexium, the assumption we shared with you is that we don't expect any generics this year.
In terms of additional assumptions supporting the preview, we'll share those with you in February. If you don't mind waiting until this full year results. Marc, do you want to cover the balance sheet question?
Yes, I will try. First of all, in terms of balance sheet, let me talk a little bit about where our financial commitment will be for next year. Obviously, we will continue with our progressive dividend policy. We will continue to spend money on CapEx and externalization. As we are today, our gearing ratio or leverage is relatively limited, I do not expect any evolution or big evolution on the leverage on the gearing itself. Our balance sheet should be more or less what it is today. There shouldn't be a major impact on the balance sheet next year.
Thanks, Marc. We'll certainly have more discussion on our Investors' Day on that topic as well. How do we intend to deploy our capital over time? Ed, do you want to jump in and cover the IO question?
Thanks very much. We could talk a lot about this. Just very briefly, the IO programs are very broad now and moving very rapidly ahead. Just to highlight a couple of things, the registration trials, ATLANTIC and PACIFIC, are moving ahead very well. The combination trials will start as soon as the dose and schedule is finalized, which should happen very shortly. Those combination trials are going very well. I should just mention a number of other combination trials that are progressing in the Bria-IMT area and with tyrosine kinase inhibitors, for example, with PD-L1 and OX40 and AZD9291 and with vaccines. There's a lot of activity for those. The program is moving ahead very well. For sure, there'll be detailed updates at ASCO, I don't want to go into much more information about specific conferences where data will be presented, but it will be.
Thank you, Ed. Let me move to Nicolas Guyon at Morgan Stanley. Nicolas, do you want to go ahead?
Yeah. Hi. Thanks for taking my question. I have two, please. The first one is on PD-L1 stratification. It seems that there is a growing consensus about the need to standardize PD-L1 test and cutoff for PD-L1 positivity. Could you remind us which assay and cutoff you are using? Or at least tell us how it compares versus Merck's 1% cutoff and Roche 5%? The second question is about emerging markets in China. After another strong quarter, China now represents roughly 40% of emerging market sales. What are the latest developments there, and do you see any risk of being so dependent on one single country? Thank you.
Thanks, Nicolas. Maybe let me cover the emerging market question, and Ed can cover PD-L1 in a second. We see strong growth in China, but as I mentioned, we also see good growth outside of China. We see a growth of about 9% outside of China. We've seen very strong growth in Russia in the recent months, in Brazil, in a variety of other countries. We are now also investing in Africa, which we see as a substantial growth potential. It's not our emerging market story is certainly very much driven by China, but also by the other countries. It's not a China-only story. As far as China, so far we don't see any substantial change. We have to accept that certainly the growth rate we are experiencing this year is very nice to have, but probably cannot be sustained at that level forever.
If you move into next year, we are assuming a growth rate that it would be a little bit lower than what we experienced this year, but certainly still very healthy, and we're still aiming at growing faster than the market in China. Again, we've seen very nice pickup of growth in Brazil. We've refocused our business behind our priorities. We've increased our investment in some places, and really nice development both in Russia, Brazil, and many other countries. Ed, do you want to jump in with the PD-L1 question?
Sure. I wasn't able to hear all of the question, I think it referred to the PD-L1 assay. As we are in a partnership with Ventana, it is delivering a fully validated companion diagnostic that's implemented in the clinical trials. The cutoff is based on data, we're using that in prospective trials moving forward.
Nicolas, does that address your question or?
Can you provide any figure for the cutoff that you are using?
We are using, actually, Ed.
There are a lot of technical details that we've not disclosed. It is data-based, it is fully validated, and it's incorporated into the ongoing clinical trials.
Okay. Thanks, Ed. We move to Emmanuel Papadakis at Barclays. Danny, do you want to go ahead?
Yes, good afternoon. I had a couple questions around other operating income, and in particular as it relates to 2015 and your guidance that you've provided. Can you confirm that the Myalept divestment of $325 million will be going through core operating income? Can you provide any other additional one-time income that you're anticipating within your guidance for 2015? I'm conscious that Nexium 24HR has sales milestones potentially payable up to $300 million, and I wanted to know if you were making any assumptions around receipts of those in 2015. Two other things, if I may, just if you could come back to your assumption around generic Nexium launch in 2015. Is it a conservative assumption? I appreciate you're not disclosing at this stage, but as of January, or are you assuming something around mid-year?
If you could just provide a little bit more flavor to that. Just lastly, you are presenting data on sifalimumab and anifrolumab at ACR. Have you made a decision to move forward into phase III with either of those assets?
Good, thanks so much, Danny. I'll ask Briggs in a minute to cover the sifalimumab question. Marc, you could cover the question about Myalept and others. Just maybe cover the Nexium 24HR launch. As I said, the assumption we are disclosing is that we assume no Nexium generic launch this year. As far as the other assumptions, we will share this in February when we meet. Maybe before Marc covers this Myalept question, just a general point, that we have a business model that is focused on the three core therapy areas. In oncology, in cardiovascular metabolism, and in respiratory, we basically have decided that by and large, we will develop and commercialize those products by ourselves. Maybe that here and there we have a collaboration, a partnership, but by and large, we want to do the development and the commercialization ourselves.
We also have very good scientists, very good science in what we call the opportunistic therapy areas of anti-infectives, but also neurosciences. For instance, in neurosciences, you saw that we have a BACE inhibitor. We have decided to partner this one because we think we cannot do this ourselves. We don't have the resources, we don't have that capability, so we partner. You probably also saw that the FDA gave us fast track designation for two monoclonal antibodies, one for the prevention of Pseudomonas infections, the other one for MRSA. Those are two very exciting assets coming out of very good science in our labs at MedImmune, in that instance. Here again, we'll have to look at how do we go to market with those products that are important to patients. We may partner them.
The point I'm trying to make is we have two parts in our business model. One part is we do ourselves, the other part is we partner or license out. We keep the innovation engine to generate value for patients and value for the company. We may redeploy this innovation engine to ourselves in the years to come at some point. In the meantime, these innovation engines will generate value for the company, and we recognize this value as part of our ongoing business model. Sorry about the long introduction. Marc, do you want to cover the specific question?
Just to answer your question directly. Yes, the revenues we are going to generate from Myalept are going to be booked as other operating income, but just want to maybe adjust the figures. The amount of $325 million obviously will not flow directly into the other income since we have on our balance sheet an intangible of a bit more than $100 million. Then we will also have to pay some tax on this transaction. On the other income would probably be slightly higher than $100 million. To answer your second question, on the OTC Nexium U.S. sales milestone, the answer is yes. This milestone is assumed to be received over the course of 2015. It is accounted for in our planning assumptions.
Thanks, Marc. Briggs, do you want to cover the last question?
Danny, you'll remember we had a little further description of our pipeline update at the first half. We show you the pivotal study starts, the pivotal study decisions, and pending decisions. The pending decision in that category was which of the two molecules we would take into phase III. We have not made an official decision yet to progress that program into phase III.
Thank you, Briggs. Mark Clark at Deutsche Bank. Mark, do you want to go ahead?
Yes. Good afternoon, gents. A couple of questions. Firstly, I wonder if you could just give us slightly more explanation as to what exactly is happening with the RSV change in recommendation, and does this have any implications for your development of follow-on products? I see there are a couple in early development. In other words, does it sort of remove the attractiveness of the market? Secondly, a question for Marc on accounting and Nexium. As I understand it, you moved to a sort of accruals basis of accounting on Nexium the day generics launch, and that presumably would also involve some write-downs on inventory, et cetera. I know it looks unlikely today, but in the event that the FDA rushed to approve generics and we had generic launches before the end of this year, would that change your guidance? Thank you.
I assume, Mark, you mean the guidance for next year, or do you mean for this year?
For 2014. 2015 would probably not change a great deal.
Luke, sorry, do you want to cover the RSV question, and then Marc could take the other one?
Sure. I think based on past experience when we had guideline changes in 2009, we do clearly expect this to place pressure on volume. This is driven by payers adopting the guidelines, and that tends to happen relatively quickly. We are mid-season, so it may take some time. Just like to mention that these guideline changes are inconsistent with our approved label, and we believe they're not in the best interest of patients, and we'll be working with stakeholders to seek the best outcomes for patients. I think Q4 and Q1 are historically the stronger months for this product, so we'll have a full picture at the end of the year.
Over time, Marc, you would expect that will play out over a period of time. You should assume that the volume of Synagis will be reduced by 50% simply because these guidelines really reduce the volume used, and they tend to be very well followed. We certainly expect a substantial impact. As far as the development of our new products, this is not changing anything. We're basically proceeding and, if we have strong clinical data and a differentiated product that can create value, we'll go to market with those products. We could talk about these products actually at the investor day, because those are quite interesting products. Should I move to Keyur Parekh? Keyur, do you want to go ahead, at Goldman Sachs?
Sure. Thanks, Pascal. I have two broad questions. First, on accounting. Marc, if I could just understand more broadly how you differentiate between items that are core and items that are non-core. It appears that the milestones that you guys pay tend to move to non-core and milestones you guys receive tend to be included in core income. If I could just get a broad sense of what it is that, how you evaluate those decisions, that would be helpful. Pascal, secondly, as you think about the R&D budget beyond 2015, given that a lot of the immunotherapy programs would be in full swing in 2016 and 2017, just if we could get some sense of what it is, how should we think about the ramp-up of R&D costs beyond 2015? That would be helpful. Thank you.
Yeah. First of all, I should apologize to Marc. We didn't cover his second question, actually. Sorry, Marc, about this. In fact, our Marc here could cover Marc's question and also Keyur's question at the same time. Do you want to cover those?
Yes. I will try to do it in sequence. For the first question, which was basically the impact of introduction of a generic in the U.S. First of all, there are two impacts. The first impact is on any possible inventory that would be in the channel. This inventory is not very large. As we come towards the launch of a generic, we tend to reduce the level of inventories. The larger impact is on the accrual of the rebates. That's where the impact is larger. As you have noted, when we arrive in the generic era, we tend to book, to take the accounting in a different manner to avoid any further impact on our accounts. Regarding the guidance for 2014, the guidance which we have revised today take into account no launch of generic in 2014.
Conversely, if you ask me, if it was launched earlier, would there be an impact? The answer is yes, but this is not our assumption today. Let me address now the issue of the core versus non-core. We have a convention which we have adopted years ago, which is basically very close to what other peers in industry do. We do amortize our intangible for non-core. We do exclude from this the impairment and amortization on our IT assets. Some other companies do include them. We exclude them. The rest is the global restructuring program, which we feel would unbalance the underlying results. We take those out and put them in non-core. The last question was on the evolution of the R&D 2016 versus 2015.
We believe that the R&D are going to remain at a high level, they should abate a little bit in 2016 versus 2015.
Thanks, Marc.
Follow. If I'm hearing you correctly, 2016 R&D should be lower than 2015 R&D. Is that a correct interpretation of what you've just said?
Right, actually.
Yes.
I don't think you should necessarily assume today will be lower.
I think it will also depend on the progression of our programs and everything. We're not providing guidance for 2015 today, and we're certainly not providing guidance for 2016. You asking me whether they're going to remain at high level, I think the answer is yes.
Thanks, Marc. Jo Walton at Credit Suisse. Jo, do you want to go ahead?
Thank you. A couple of products specific and a couple of broader ones. On the product specific, you've now bought the Almirall respiratory products, and I believe you have the right to opt in if you want to in the U.S. Would it be reasonable to assume that you would start to take a role in the promotion of aclidinium in the U.S.? You've made a comment that you're expecting a low single-digit negative pricing in the U.S. for next year, which is presumably a bit more of a headwind than you've had in this year.
Would it be fair for us to assume that that is the price that you have paid, broadly speaking, so that in all of your major categories, excluding SYMBICORT, where we know that you will be excluded for your diabetes products, et cetera, for everything else, we should broadly assume the same sort of access to formularies for 2015 as 2014? My other couple of questions, just a technical one on the cash flow. Very strong working capital inflow in the first nine months of this year. Is that something you can sustain for the whole year, or is that just something which will reverse, it's just a timing issue? A final broader one, and I know it seems to go back to this concept of your guidance for next year, but I'm a little bit confused.
You appear to be saying that broadly speaking, your earnings, all other things being equal, should be roughly flat for 2015 over 2014. Yet in 2015, presumably at some point, we would prudently assume some form of NEXIUM. We may see some form of PULMICORT go. We know that we've got a tougher period for SYMBICORT and with Synagis. Is there really so much flex in your cost that if we collectively assume some small reduction in underlying sales, you can make that up and that there really is an ability to take out SG&A so that we can still have flat earnings against declining sales?
Okay. Thanks, Jo. Let me cover a few questions, and I'll leave the rest to Marc. Almirall products in the U.S., it is a consideration indeed, but with these kind of issues, you always have to be able to come up with something that makes sense for everybody. Certainly, something that we might consider. For the time being, we're very focused on launching in Europe and looking at how we can leverage this franchise in the emerging markets as well. As far as your question about the pricing in the U.S. and access, I think first of all, when you say we're going to be excluded in SYMBICORT, there will be access challenges in the U.S. in 2015, there's no doubt. We certainly will keep trying our best to improve our access or reverse the difficulties, the challenges we're facing.
Certainly overall, you're absolutely right to say the access will become more challenging, and there will be a price impact, which is the price we've built in. Across diabetes, we don't expect specific issues. We don't expect new specific issues, but certainly again, an increasing price pressure for this product. Again, that's why overall, across the portfolio, we assume a low single-digit price decline. Finally, the guidance. I think you should see that our growth platforms are growing, so we certainly are expecting sales growth from those, even though we are losing NEXIUM next year, number one. Number two, we certainly will manage our costs appropriately next year, as we said before. I guess, I'm not sure what else I could tell you. Of course, you might wonder, you might question our preview for 2015.
No. First of all, your first question on the cash flow. I think when I presented to you in, I think it was in February of this year, I mentioned the focus that we would have on the cash conversion cycle. I think some early work has provided very good results on the payables, on the receivable, as well as the inventories. We will continue with this effort, which has already, as I said, produced some good results. We will continue with this effort over the following years. There should be some continuation of that in the coming years. Regarding your question on, can you manage your cost in a declining sales environment? The answer is yes. We need to provide enough ammunition to align the pipeline, and therefore, we will look at our cost base as we have done in 2014 and 2015.
The only thing I will tell you is so far we've done what we said we would do. We've said we are going to manage our investment and our cost base to be able to deliver the Core EPS we've guided to. Beyond that, it's going to have to be a lot more specific. Marc, do you have anything you want to add?
We'll continue to do that. We'll try to redeploy as much as we can. We have seen today that we have announced the divestment of Myalept. This is going to help to a small extent. Basically, we'll look at our cost base, and we'll monetize asset or partner assets when we can't develop them on our own.
Thanks, Marc. Seamus Fernandez at Leerink. Seamus, do you want to go ahead?
Thanks very much for the questions.
Maybe just as a first question. You talked a little bit about EPANOVA. Just update us on what your hopes are from a 38,000-patient study and what the investment and costs are relative to that study, particularly in the context of meaningful other advances occurring outside of the space with PCSK9 inhibitors, in particular as a potential challenge. As well as just sort of the payer cost environment, just trying to understand that particular investment. Second, Pascal, you're getting lots of questions on the sort of leverage opportunity year-on-year. As we think about business development, it seems like you do have good balance sheet flexibility. In terms of an interest or a willingness to do potentially larger acquisitions that leverage your current and existing cost base, would there be a willingness to consider those types of transactions in the 2015-2016 timeframe? Thanks so much.
Thanks, Seamus. EPANOVA, I think it's important to keep in mind that the PCSK9 suddenly would be a substantial improvement, but we believe there will remain a risk associated with triglycerides, and of course, we have to demonstrate this, and that's the goal of this study. We're not the only people believing that it could be the case. If you look at the steering committee of that study, it includes some of the most prominent, most important opinion leaders in cardiology and lipidology around the world. Those experts believe in the possibility to show a benefit by reducing triglycerides. Of course, we are in a risky business. We never know whether our study will be positive or not. If it is positive, it will actually be the only treatment that has demonstrated cardiovascular benefit from the reduction of triglycerides.
That's essentially what we are hoping to demonstrate with this program. As far as the balance sheet opportunity, yes. Essentially, what we've done so far is focus on building our three core therapy areas. In fact, as Marc said, monetizing some of the non-core assets and also turning the opportunistic therapeutic areas into another business model. We have two business models going. It's really been based on small to mid-size acquisitions or partnerships. Having said that, if we did find the right opportunity that would lead to a larger transaction, we would also consider it. The key is, as we've said many times before, including in the discussions we had with another company not so long ago, the key for us is always, do we believe we can execute? Do we believe we can create value?
Do we believe there is a strategic value in a merger? Can we add value? Is there a synergy, can we execute without distracting the focus on the pipeline? Those are conditions that are hard to meet, I must say. If we were able to find an opportunity addressing those, and we could create value for our shareholders, we would definitely explore it. I move to Mattias Ekblom at Danske Bank. It's an email question, so I'll read it for you all. The question Mattias is asking is: Can we assume you will update the market at the Investor Day on your progress towards 2017 and 2023 targets that you shared earlier this year? Should we see two targets as extraordinary events in light of circumstances around your company earlier this year? No, the answer is a very simple yes. Our targets remain our targets.
We are still aiming at 2017 sales in line with 2013, we still are aiming at the 2023 sales forecast that we communicated earlier this year, which actually, by the way, was not in light of circumstances. It was actually based on our long-range plan developed several months before, just as a quick reminder for everybody. No, those targets are still very much part of what we're trying to achieve. Steve Scala at Cowen. Steve, do you want to go ahead?
Yes. Thank you. I have three questions. First, a clarification on the 2015 guidance. You said that 2015 will be no less than the lower end of the range of the updated guidance for 2014, but 2014 guidance is a single point. I'm sure I'm missing something, but would you please clarify? Second, would you please update us on the status of SYMBICORT generics in the EU? Lastly, Lilly said on its Q3 call that the AstraZeneca BACE inhibitor had the opportunity to be differentiated from the Merck BACE, in part due to different chemistry. Unless you'll detail the differences at the analyst meeting, I'm wondering if you could amplify on these differentiating features now. Thank you very much.
Thanks, Steve. The BACE inhibitor, maybe what we could do is cover this at the Analyst Day because I'm reminded here that we are running out of time. Marc, you could cover the overall guidance in a minute. I'll just cover quickly SYMBICORT EU analogs. We are basically seeing the introduction of SYMBICORT analogs across Europe. That continues. This year it had an impact on price. As you saw, we grew volume by 6% but declined in turnover by 1%, certainly a price impact. Next year, we expect to continue the negative price impact from the introduction of those analogs. The one thing that is important to keep in mind, though, is that in many countries, when you look at how much share those analogs are capturing, it's usually not so much actually.
Usually, they don't capture much because the devices are not the best, and to some extent, physicians are getting a little bit confused by the number of products that are being introduced, including analogs. In most cases, we are able to maintain our market share. We lose price, of course, because the payers are cutting reimbursement our share and our volume, and we saw that this year. We expect sort of a continued trend in that direction next year in Europe. Marc, do you want to cover the guidance question?
Yeah. I think, first of all, it's not a guidance. We said we would provide a guidance in February next year. What we have given you is a preview of what it could look like in 2015. Your reference to a single point, I think you need to understand the words, as we said, a decline of about 10%. When it's about, of course, it can go slightly under 10%, slightly above 10%. We have also given you a variation for the impact of Forex that can be expected, which is about 5%. Again, you have some variation around the 5%. If you apply those two variances, you can certainly reach a range, which is a range that we are considering for next year.
Right.
When you have the range, you can say, you can take the lower end of the range, and we are going to be no less than the lower end of the range. This is the way it's constructed. Again, it's not a guidance. We'll do that next year in February.
I'll take the last question from Simon Baker at Exane. Simon, go ahead.
Thanks so much. Most of them are answered. I've just got one left. I see from slide 16 that it looks like SYMBICORT in Europe faced about a 7% price decline. I was wondering if you could give us an update on the European pricing environment now and your assumptions for 2015. Thanks.
Yes, Simon. Luke, do you want to cover this one or yeah?
I think, this is part of the structure of the market there. We see national, international reference pricing on regular intervals. The changes related to SYMBICORT in the last 18 months were, France and Germany, for example. I think the key thing is the point that Pascal made before is that there's some resilience around this device. The market share conversion that we're seeing is low and will defend our position.
Simon, maybe we can't be too specific with SYMBICORT. The one thing I could give you is a general number across the portfolio in Europe. We also expect low single-digit price pressure across the entire portfolio. That's kind of our expectation across all the products, with some products being affected more than others. Certainly SYMBICORT is affected by the launch of analogs. Let me stop here and end the session, I would like to thank you very much for your attention and all your great questions. As I close, just like to remind everybody of our 2014 upgraded guidance. We're very pleased to see the sales trend so far, and we expect to see some of that benefit into 2015, even though, of course, we are well aware that next year will be a substantial headwind.
A lot of our products and priorities are growing very strongly. The preview for 2015 hopefully gives you a sense for what we're trying to achieve and the approach we're going to take to our business in 2015. Invest where we still need to invest, but also manage our costs so that we can deliver a reasonable Core EPS. Finally, but very importantly, our pipeline is progressing very nicely, and it's very exciting for all of us. With this, I hope I can see many of you at our Investors Day very soon. Thank you very much, and have a good rest of the day.