Roche Holding AG (ROG.SW) Q3 2017 Earnings Call Transcript
Published at 2017-10-19 17:05:05
Dr. Severin Schwan - CEO Daniel O’Day - CEO, Roche Pharmaceuticals Roland Diggelmann - CEO, Roche Diagnostics Alan Hippe - CFO and IT Officer
Luisa Hector - Exane BNP Paribas Steve Scala - Cowen Tim Anderson - Bernstein Vincent Meunier - Morgan Stanley Sachin Jain - Bank of America Merrill Lynch Matthew Weston - Credit Suisse Sam Fazeli - Bloomberg Andrew Baum - Citi Richard Vosser - JP Morgan Philippe Lanone - Natixis Keyur Parekh - Goldman Sachs
Ladies and gentlemen, good afternoon. Welcome to the Roche Nine Months Sales 2017 Conference Call and Live Webcast. I am Sari, the Chorus Call operator. I would like to remind you that all participants will be in listen-only mode and the conference is being recorded. After the presentation, there will be a Q&A session. [Operator Instructions] The conference must not be recorded for publication or broadcast. At this time, it’s my pleasure to hand over to Dr. Severin Schwan, Chief Executive Officer of Roche Group. Please go ahead, sir. A - Dr. Severin Schwan: Welcome to our Q3 call. This is Severin speaking. You have seen sales up by 5% in both pharma and diagnostics, very much driven by our new product launches. If we turn straight to page seven, you see very good growth in the United States, driven by the new product launches, Ocrevus in particular, we’ll come back to that. Good sales in Japan and international relative to the market. But you’d also see as expected an impact in Europe. We have seen a decline overall of minus 1%, very much driven by the entry of biosimilars for MabThera and general price pressure. So, we are closing at mid single-digit sales for the year. And again, if we turn to page nine, really very happy to see the successful launch of the new medicines. As you can see on this chart, 900 million, and this is over 60% of the growth in pharma is driven by Ocrevus, Tecentriq and Alecensa alone. We had important regulatory milestones over the quarter including the U.S. Priority Review for Perjeta in the adjuvant setting; and you see on page 10 a number of additional important milestones as we look at our portfolio. Now, up at 18 Breakthrough Therapy Designations for alone this year in 2017, putting us very much at lead in the industry and reflecting the level of innovation of our portfolio. If you look forward, you can see page 13, really a number of readouts for Tecentriq. We expect eight trials to readout until mid of next year, five in lung, three in three other indications. So, a very rich pipeline as far as Tecentriq and the various combinations are concerned and Dan will certainly cover this in more detail. And we also expect the readout for the non-inhibitor patients in hemophilia A. So, product launches of new medicines is at a record high; and based on the good performance, very much again driven by the new products, we expect mid single-digit sales growth, EPS to be broadly in line with sales growth, and further increase in our dividend. And with this, I am happy to handover to Dan. Daniel O’Day: Thanks Severin. So, good afternoon, good morning everybody from my side, and we will go right through slide 18. Again, strong growth in pharmaceuticals division, year-to-date growth of 5%. The geographical trend, basically what we had seen in previous quarters and that we had spoke about and we will continue, the U.S. really strong growth, largely driven by the new products, Ocrevus, Tecentriq, Alecensa, and also by a strong immunology franchise. In the EU, strong Perjeta sales, strong Actemra sales, but more than offset by the weaker Rituxan sales, partly due to the first biosimilars here and also weaker Avastin sales as expected, predominantly due to the breast cancer delisting in France. In Japan, good growth driven by Actemra, Perjeta, Rituxan. And in the international region, the 4% driven by China predominantly and Brazil. And I would say that for future quarters, we expect to see the different growth dynamics between the U.S. and the EU to continue in the coming quarters. Just to make sure everybody understands obviously that we have got the U.S. business, will continue to be driven by the upcoming launches with the later entry of biosimilars whereas Europe is one year behind with the launches by the nature of the reimbursement process and experiences the biosimilars earlier. Moving to slide 19. A nice picture of the overall contribution of the sales, new products driving the growth, increasing contribution from the recently launched products in the immunology franchise. Together, the three recently launched products contribute 900 million to additional sales. On top of that, Perjeta contributed another 238 million, and in the immunology franchise driven by Xolair, Actemra, and Esbriet, yet another additional 450 million in sales. I’ll just touch on some of the products that I don’t touch on in the following slide. So, one is Activase, really nice growth of 14%. Pegasys and Tarceva remain impacted by the competition as report and you see of course Tamiflu influenced by the generic erosion. So, if we focus then on slide 20 on the oncology portfolio, year-to-date sales growth was 3%, driven largely by the HER2 franchise, by the CD20 franchises and by Tecentriq and Alecensa. I’ll touch on the HER2 franchise in following slides. So, let me, on this slide, cover Avastin, sales down minus 2%. In the U.S., the sales remain impacted by competition in one of the indications, in the lung cancer indication with the adventive immunotherapies coming into the first line lung setting. In the EU, really overall stable patient shares across all indications in the EU. And it’s really impacted predominantly by the delisting of first line breast cancer indication in France. And Japan, you see the return to growth after offsetting the mandatory price cut that was instituted last year in Japan. Moving to the CD20 franchise. That franchise grew 3%. And of that 3%, MabThera, Rituxan and the oncology franchise growing about 1% and Gazyva growing about 40%. And the Rituxan growth was driven by the U.S. and international. Of course, we saw, as expected, a decline in the EU, partly due to the biosimilars and the subcutaneous formulation of Rituxan, which was now launched in the United States as of quarter two of Rituxan. It’s really off to a very good start, I can say. Gazyva grew 40%, reached sales of little over 200 million. Pleased to see that in quarter three, Gazyva got the approval in the first line follicular lymphoma segment, which is really the first major indication for Gazyva and large preparations for the first line setting in the U.S. are fully on track, received the priority review and already included in the NCCN guidelines. Moving down the list, Tarceva continued decline due to in class competition. Tecentriq reported year-to-date sales of 355 million, driven by the uptake in bladder and lung, and the bladder and lung split was around 60 to 40 in quarter three with an increasing contribution from lung as expected. In addition, Tecentriq achieved the EU approval in quarter three for its second and third line lung and first line and second line bladder. So, we’re pleased that we had the full indications that we had submitted approved for Tecentriq and be launching that shortly. Alecensa in second line lung cancer grew a 102% year-to-date, reached sales of 244 million following the second line EU approval in quarter one of this year. And we received a positive CHMP opinion for the first line setting in Europe in quarter three. And also in the U.S. for Alecensa, the first line submission received priority review. It had already received a breakthrough therapy designation. And importantly, Alecensa has already been included in the NCCN guidelines, not just included, it’s listed as a category one listed at a preferred option for the first line setting. Cotellic and Zelboraf is a tale of two stories. The combination Cotellic growing at around 47% and Zelboraf is down around 23%. The first line market shares for the combination remained stable but in the EU, the Zelboraf monotherapy share has declined sharply. I remind you, as we think about next generations of therapies with melanoma, we in quarter four also expect the first patient to [indiscernible] 170 that’s a triple combination Tecentriq, Cotellic and BRAF -- I’m sorry, Cotellic and BRAF wild-type patients. And we have already started the Phase 3 trial in the BRAF mutant patients with Cotellic, Zelboraf and Tecentriq. So, moving to the HER2 franchise on slide 21, good strong sales of the HER2 franchise, Perjeta growing 17%, and that’s really strong demand in all regions at this stage. Kadcyla growth was driven by the international regions and U.S. and EU. And then, Herceptin, I think we’re starting to see the volume momentum has been slowing in the developed markets because we’ve seen the penetration -- a high penetration obviously and the momentum for the prolonged treatment with Perjeta in first line setting slowing down now because of the high penetration, also in Europe of the Perjeta use in the front line setting. And importantly, an update on APHINITY. We were very pleased to see that the FDA had granted priority review for the adjuvant setting for Perjeta and Herceptin. The PDUFA date is now set for January 28. We had very good discussions with the agency on that. And EU filing for APHINITY has been completed, as you know. So, we are very much looking forward to bringing that new option for patients in the front line adjuvant setting. Turning to the immunology business on slide 22. Immunology franchise growing at 8% for quarter three; year-to-date, it’s 9%. Xolair, again, a high mark, ongoing launch in the pediatric asthma indication, continued halo effect into the allergic asthma and strong CIU growth. I don’t talk about Xolair anywhere else. So, I think it’s important to note, we’re continuing to develop this medicine. Two Phase 3 studies were initiated in chronic rhinosinusitis with nasal polyps, and the scientific rationale for the data in Xolair encourage us that the Xolair can make a big difference in this debilitating disease. Actemra, solid growth of 13%; EU, 7% in the quarter; and GPA approval was achieved this past quarter, in quarter three. In the U.S. still good strong subcutaneous uptake, increased IV diffuse, good high awareness and the growing success of the GCA launch in the United States which we seek approval for earlier. And we achieved the CRS approval in quarter three as well. MabThera/Rituxan in immunology continues its growth in rheumatoid arthritis and also vasculitis. Esbriet, I would just point out, grew 3% in the quarter. It continues to hold its market leadership in the U.S. and EU. Good growth in the United States, in particular this past quarter. Market shares are above 60%. We are making headway into the mild patient segment with Esbriet but it is -- it takes a lot to move that needle. It’s a bit slower than we expected. There is still less than 40% of patients received -- receiving any of the IPF therapies in the mild to moderate segment. But, we are continuing to work on opportunities to increase the awareness in that patient base because it’s really absolutely critical for this debilitating disease. And I would just point out that in quarter two we launched a more convenient tablet formulation, which is being well received by the market as well. Turning to slide 23, the ophthalmology franchise, Lucentis year-to-date growth of plus 4%; it’s driven by the launch of the prefilled syringe earlier this year and also by some of the new indications we have this year, the first-in-class launches in mCNV and diabetic retinopathy without DME. So, these new indications are also supporting. We expect -- and I think you can see from the graph that certainly Lucentis has stabilized now. And I would also say that importantly we’ve -- the enrolment of the Phase 2 port delivery study, the so called LADDER study was achieved ahead of schedule and the data readout for this is expected in 2018. And then, finally, I would also point out that our bispecific antibody, this is the anti-VEGF/Ang2, we expect data on in 2018. Turning to slide 24. Clearly, the highlight of the quarter in terms of new launches, in terms of magnitude was Ocrevus. Ocrevus sales in quarter three reached 308 million, up from 192 million in quarter two. The early launches clearly indicate that this is amongst the best launches in the MS space, in terms of the track and trend that it’s on. The growth is driven by a nice mix of RMS and PPMS. It’s a valid 60-40 split, 60% RMS, 40% PPMS. Clearly, there is a -- there is some patient bolus effects, we think that’s primarily in the PPMS setting, because of the fact that there were patients waiting for therapy and no approved indications. And as usual, it’s difficult to forecast the patient bolus at this stage. We estimate around 17,000 patients have already been infused so far. Good, strong patient volume, highly encouraging, speaks to the unmet medical need and the role that this -- that the profile this medicine brings. We do expect in quarter four to have some patients returning for their second infusion, those patients that were treated early in our launch period. Again, a little difficult to exactly forecast because patients come in at different times, and you have holidays and other things. But, we really start to see as we enter into the later part of November into December, the retreatment occurring as well as continuing new patient generation. I would just give you a little bit more color on this, in-roads into all treatment lines in RMS. We have around 70% of patients coming from switches in RMS and around 30% are truly naïve patients or previously discontinue patients for some period of time. And the switches are really coming from the entirety of the MS medicines group, Tecfidera, Gilenya, Tysabri, Copaxone, the Interferon, Lemtrada. I mean, it’s fairly evenly distributed; there isn’t one that’s overly accountable for the switches. And in PPMS, as you probably expect, 55% of the patients are naïve or discontinued, whereas 45% were switchers from other medications. The last thing I would say on the performance is that the adopters of Ocrevus is really from a very, very broad base of physicians. And we’re very encouraged by that and we continue to have very good insurance coverage in the United States as well. So, that’s all going extremely well. On the EU launch, we are fully on track for the preparation here, and we expect the CHMP positive opinion before the end of the year. I would say, we’ve got reviews going on into 50 other countries right now with about eight countries approved so far for Ocrevus. So that ties up the performance to-date. I would just move to the innovation section, picking up on slide 26. We have two additional breakthrough therapy designations, were obtained in quarter three, in hematology, one is Venclexta and low dose cytarabine in the first line untreated AML, and polatuzumab and bendamustin and Rituxan in the relapse/refractory DLBCL. Polatuzumab was the latest breakthrough therapy designation and also received the prime designation from EU. And the Phase 2 data that we now have in-house will be presented later this year at ASH. Overall, out of the 18 breakthrough therapy designations, six of these are in hematology, four for Venclexta and one for polatuzumab and one for Gazyva. Since we haven’t talked about the entirety of the hematology franchise for a while and there’s a tremendous amount going on there, I just wanted to cover two slides, so starting with slide 27. I mean, we have tremendous efforts around this space and there’s a lot of development on the innovation side. So, as you can see from this graph, the CD20 treatment has become the backbone for around 50% of all hematology cases, including CLL, DLBCL and follicular lymphoma. With Gazyva, we’ve been able to shift again the standard of care in CLL and indolent non-Hodgkin’s lymphoma patients. I’m very pleased to say in quarter three, as a I mentioned, we got the approval in Europe and PDUFA date is set in the U.S. before the end of the year, December 23rd for Gazyva in the United States. And going forward now that we have established or identified where Gazyva can replace Rituxan as a backbone, we’re looking at now adding novel NMEs on top of CD20 to further improve the standard of care. And in CLL, we have two Phase 3 Venclexta combination studies. One in the first line setting CLL14 and one in the relapsed/refractory setting, the MURANO study where we have the breakthrough therapy designation. We just announced, as you know, a positive outcome for the MURANO study at the interim and we’re currently preparing to submit that to regulatory authorities and also to a conference for publication of the data. As mentioned already on the previous slide in DLBCL, we got a positive Phase 2 result for the combination of polatuzumab and Rituxan bendamustin. And based on the Phase 2 data of that polatuzumab study, we received a breakthrough therapy designation and a prime designation in the relapsed/refractory setting. And we also initiated now the pivotal Phase 3, evaluating pola plus R-CHOP in the front line setting of DLBCL. So, you can imagine, we’re extremely excited about shifting the standard of care with this combination. And finally, we’re also taking our novel molecules and the pivotal Phase 3s in additional hematologic malignancies that weren’t previously covered by CD20 such as AML and multiple myeloma, and you see that represented on this slide as well. Now, just quickly to touch based on slide 28. This is kind of the entirety of our program, 12 molecules in combination testing. And highlighted in dark blue is the progress we’ve made over the past nine months in terms of moving medicines through the development channel. I covered everything upto Idasanutlin on the previous slide. So, I would just make a couple of comments on the bispecific antibodies or anti-CD20/CD3 trispecifics. We expect the first data from these programs in 2018 and we’ve also extended our Tecentriq program in hematology with Tecentriq now being tested in four different indications, AML,NHL, MDS and MM. So, a really comprehensive hematology portfolio which we are looking forward to the development of in the coming years. Turning the attention to something much more immediate, and that’s APHINITY, slide 29. Again, to reemphasize that we do have the priority review, PDUFA date for January. I remind you that the patient population that we are targeting here is the 75% of the HER2, of those currently treated with Herceptin in early breast cancer, which is the node positive, hormone receptor negative and some other high risk category patients. And our APHINITY filings are really on track, both in the U.S. and in Europe in terms of the submissions and also the dialogues. I would just point out. Some of you were at ESMO. We had a very good discussion, a well-attended satellite symposium, and we received very good feedback from the TAEs, multiple congress interactions on general endorsement for Perjeta and Herceptin and the benefit it brings to patients considered high risk in the clinical practice setting. So, on slide 30, you see an update on our emicizumab. We’re awaiting the results of HAVEN 3 that we still expect this year and obviously we’ll report out to you as soon as we get those. For the inhibitor indication, we have a PDUFA date of February 23rd and we are also on track with our HAVEN 4 results on monthly dosing that are expected in the first half of next year. So, we will be keeping you informed on both the trial results in the non-inhibitor and obviously the approval in the United States as we track that for the rest of this year. So, in summary, I just want to close on a couple of points about the outlook. Moving to slide 32. Slide summarizes that we have a tremendous amount of readouts in the cancer immunotherapy setting and the hematology setting. Overall, we have eight Tecentriq Phase 3 studies and five indications reading out over the next several quarters. With IMpower150, we have the first look at the combination of Tecentriq and chemo with and without Avastin. That data is still expected, still on target for between now and the end of the year. I will remind you, we have the co-primary endpoints in those trials, and in fact all of these trails with the exception of colorectal cancer for the reason of the nature of the late state colorectal cancer. But, all the rest have PFS, OS endpoints. And we would expect that if we get only get only PFS in the quarter four that the OS would readout between three and six months later. So, not far after the PFS, given the design of most of these trails and certainly the IMpower150. We do have an additional IMpower150, very important to point out, four additional Phase 3 chemo combo studies in lung cancer reading out in the first half of 2018 with a very thoughtful approach to looking at different chemo backbones with and without steroids and with and without Avastin. And then, finally, I would point out the readout in the first line triple negative breast cancer and in second and third line colorectal cancer where we expect to be first-in-class. And we’ll have the readout of the Tecentriq plus Avastin in the first line renal cell following the Phase 2 data that you already saw earlier this year. And then, finally on slide 33, just to be complete and mention a few quarter three events that we have not covered in previous discussions. In quarter three, we received the approval for Tecentriq in second, third line lung, and first and second line bladder. And following the U.S. approval, we also received the EU approval for Actemra and giant cell arteritis. And then on the Phase 3 readouts, we had a negative readout for lampalizumab, for geographic atrophy due to the failure of the SPECTRI trial. So, unfortunately, that program will not be moving ahead. And as mentioned, we had the positive Phase 3 readout in quarter three for the MURANO study; that’s Venclexta plus Rituxan and relapsed/refractory CLL which we look forward to showing you that data. And then underneath the table here, the additional quarter three events that were not initially included in our table was the EU approval for our Gazyva in the frontline setting and the FDA priority review for that indication as well. And for Alecensa, in the first line setting, we got the priority review and we received already a positive CHMP opinion for Alecensa in the front line setting -- in front line for Alecensa. So, thank you very much, busy quarter. And with that, I’ll turn it over to Roland to cover diagnostics.
Thank you, Dan. Good morning, good afternoon, also from my side. It’s been a good quarter, good continued momentum in diagnostics in the quarter with 6% growth, bringing year-to-date to 5% overall for the diagnostics division. You can see the breakdown on page 35. Overall, very good performance on the clinical diagnostics setting that centralized molecular and tissue combined growing at 7%. And we continue also to see a challenging environment in diabetes care with minus 2% year-to-date. Moving to the geographic breakdown on page 36. Good growth in all regions, good geographic distribution of our sales. I’d point out, good growth in EMEA, in particular in the large markets, Germany and the UK. North America, 1%. We have seen some slowness in the United States in the clinical diagnostics in anticipation of PAMA and of the new clinical laboratory fee services, which will take effect in January 2018. So, with some softness around laboratories investments and capital [indiscernible] and we are probably looking into those laboratory fee services and the impact on the business going forward, undoubtedly this is driven by CMS in the public sector and will also have some effect on the private sector. Very good performance, Asia Pacific, Latin America, really good performance there of our E7 countries, growing at 18%. Among those, Turkey growing 25%, Russia 12% up, Brazil up 22% and China continues to grow nicely at 21% year-to-date. On the next page, some of the drivers of sales. And you can see the centralized and point of care franchise doing very well, and [indiscernible] here the combination and automation of clinical chemistry as immunodiagnostics continues to grow nicely, very strong drivers, immunodiagnostics per se say was 13%. On diabetes, the next line, I just want to remind you that we have had a 20% reimbursement cut in the public sector last year in the U.S. So, we are continuing to see some of these spill over into the private contract. Molecular diagnostics, virology is down 2%. That was within our expectations, but coming off a very high base from HCV [ph] testing in particular, which is a consequence of the introduction of the DAA, so the direct antiviral analogs, so very high peak testing in 2016 and some expected rebasing in 2017. On the other hand, HIV doing very well and continued to do well with some non-government programs, steep growth as well in Sub-Saharan African and other emerging markets. And then, you can see blood screening up nicely 4% with some -- several wins in different countries in blood screening tenders. Tissue diagnostics, overall very good picture as well as in the core advanced staining portfolio, up 10%; then primary staining doing well as well; and companion diagnostics up 32%. On the next page, this is a broader strategic context of how we’re executing against this strategy, really to implement a fully integrated core lab, allowing the labs and hospitals to really manage their resources most efficiently, allowing them to really generate profits at very high test quality. And what it takes to do that is of course multiple elements to come together, starting at the upper right. We have of course the analyzers at the backbone with the high throughput. Then moving to the left, connecting more and more disciplines. We’re the only ones that can connect molecular to serology but then also going into other areas of diagnostics, hematology, coagulation, also connecting third-party products. And all of this of course on the basis of a very comprehensive menu, adding high medical value menu and then finally of course the key to all this is also having seamless workflow and IT solutions to really being able to move the samples in the lab but also to report the results also in these central settings. And then, some new areas, which I’ll cover in a bit -- in a later slide is also opportunities downstream in digital data management. So, on the next page, 39, which is really the backbone here is of course high throughput instruments. For us, the launch of the e 801, which is the immunodiagnostics module, continues to be very successful. You can see at the bottom of the page, we’ve now more than 500 instruments in the market. This is of course supporting our immunodiagnostics franchise which is growing 13% and we have just completed the menu on the serology for blood screening, which you can see on the left. So, this is all going very well. And on the next page, page 40 is one example of how we continue to pursue high medical value tests, looking at influencing treatment guidelines and algorithms supporting this with clinical studies. And this is a new test, GDF-15, which has the ability to predict individual bleeding risk, and this is in particular important for patients with AF, with atrial fibrillation. We have about 33 million patients in the world, which have AF and which we know are at the risk of a stroke. And GDF-15 is actually a biomarker to identify the individual risk for bleeding. So, to-date, about 50% of these patients received no stroke prevention and with this of course -- with this test, we have an opportunity to better decide the administration of anticoagulant and better patient outcome. Another example on test is on the next page with Zika. And this is just a chronological review of what it took actually from the initial outbreak all the way to now having the only and the first FDA-approved test for a commercial use of Zika, and it runs on the basis of our large platforms for molecular testing, more than 300 instruments in the market of the cobas 6800 and 8800. And then, finally, we are looking beyond diagnostics testing and continuing to look at opportunities in the digital space. The NAVIFY tumor board is a cloud-based software solution for clinical workflow and decision making support. It’s building on our strengths in diagnostics and particularly on tissue diagnostics in this case and really on in-depth understanding of the workflows in the hospital. This system and software aggregates patient data from multiple sources into a comprehensive dashboard and it allows for better team collaboration around tumor board and certainly with that we’ll have an opportunity to continue to expand services and solutions in the future. With this, this brings me to my slide, which is really the portfolio review. Portfolio development is very much on track with the launches, as you can see them outlined here. And then, we’re looking forward to very much to our own coagulation testing solution, the cobas 511 and 711 in the fourth quarter. And with that, thank you very much. And I will hand over to Alan for the financials.
Thanks, Roland. Yes, a couple of remarks about the sales development and especially the currency. So, I think sales, I think everything was mentioned already. And when we talk about currency, let’s go to slide 46. And what you’re seeing here from the sales side, a very small impact here from currency, minus 41, and let me explain that on slide 47. I think what you see is that the Swiss franc has weakened against the U.S. dollar as well as the Latin American currencies and it has strengthened against the Japanese yen and other European currencies, predominantly the UK pound. What was a bit surprising I have to say is -- and you’ve seen this for sure, was a major swing of the euro in Q3. However, you might remember that we had a negative impact of minus 0.4 percentage points in the bridge here between the Swiss francs and the sales in constant currencies. At year-to-date Q3, you see we have no impact from the euro. So, definitely, in Q3, the Swiss franc got weakened against the euro by quite a margin. And in general what you see is that the impact positive as well as negative got smaller compared to half year. And with that in mind, let’s go to slide 48. And here you see the modeling that we are always doing, assuming that the September 30th currency rates remain stable. And in fact, what you’re seeing for full year is that we expect no impact from currencies on sales, on core operating profit as well as on core EPS. And in fact, when you look at the left hand side of the slide, you see where that is coming from. It’s basically coming from the point that the averages 2016 for the last three months as well as the averages for 2017 basically are the same for the last three months. So, in fact, that’s no impact, no further impact is coming here as I stated that we have reached year-to-date Q3 is how should I say, trends [ph] until year end. Good with that, last slide is 49. Severin has confirmed the guidance already. So, we are now happy to take your questions.
We will now begin the question-and-answer session. [Operator Instructions] The first question is from Luisa Hector Exane from BNP Paribas. Please go ahead.
Good afternoon. Thank you for taking my questions. On Tecentriq, I have a couple of questions. I wonder whether you can talk a little bit about how you see Tecentriq and the other IL agents being used in the U.S. And for example, the diagnostic test, are you finding that both Roche test is being used in parallel with others, just maybe some color around that and the actual usage today? And then, could you give us some more color on IMpower150 and how the hierarchy works, because you have obviously got three arms, you have got co-primary end points, how do you split the alpha, are there any PD-L1 thresholds? So, any color just as we prepare for that data to come through? And what would be the next study of the lung cancer study to report after 150? Thank you. Daniel O’Day: Thanks, Luisa; Dan here. So, yes, at this stage, in the development of immunotherapy and indications that were in clearly bladder and lung cancer, we have all primary [ph] indications as you know. So, we -- the diagnostics, as indicated in the package is complementary. And so, we’re in the later stage, as expected, later stage cancer settings. We’re seeing a very mixed uptake of practices that may use diagnostics or may not use diagnostics at that stage. We do believe by the way that that will -- has the potential to alter and adjust as we get into earlier stage patients and depending on the readouts and many of our trials. But to-date, I would say that where PD-L1 testing is going on, most physicians are quite agnostic to what PD-L1 test they are using, if they are using this. But for the most part, because trial results like Oak and others, we’re not seeing a great usage of that. I would just say, maybe just to broaden the envelope out a little bit on that that we’ve got a number of different diagnostics hypothesis that will be [technical difficulty] starting with IMpower150 where we look at tumor gene expression, the IGE, the so called IGE expression and we will be able to take a look at that in that trial and also some of our other trials to see that could be a more accurate predictor, even more accurate than PD-L1 expression by IHC. [Ph] As you know, we have published quite a bit of information on tumor mutation that was also highlighted again as ESMO. And so, we’re working actively, as we go into the frontline settings, where we expect that multiple options may be possible for patients for monotherapy to chemo combos to I/O I/O combinations to find different diagnostic methodologies that can help guide therapy selection and that’s going hand-in-hand with our trials as we speak. So, in the IMpower150, yes, it has the arms with chemo, with and without Avastin. But no, I wouldn’t give you any more perspective or insight into how the alpha is split between those arms. What I would say is we feel like we’ve been very comprehensive with those trials, both in terms of the patient numbers, the fact that from the start we had the co-primary end points built into these, so they’re powered such that if there is an OS effect and a PFS effect, we feel very confident that the way the statistical analysis plan has been laid out that we’ll be able to see that. And so, I think we now, like you, have to wait for that first readout. We have a variety of other studies reading out, as you rightly point out. And so, beyond the IMpower150 initial readout that we expect before the end of the year, we -- if the OS is not reading out of that time, it would read out three to six months later. And then, it depends a bit on what study comes in or out from there, but we’ve got IMpower130, IMpower131 and IMpower132 that would all read out in the next several quarters, again in the combination of PSS and OS. So, that’s about what I can highlight to you at this stage without being more specific on exactly what those studies are coming to. But, what I would say importantly is that we have a commitment to you to provide you with the outcome of the study results as soon as we know them. So, as soon as we know them, you’ll know them and be able to piece together the different elements of information here. Hope that helps.
And then, can you share the split of the 3Q sales between bladder and lung? Daniel O’Day: Yes. So, it’s around 60% bladder and 40% lung at present with lung increasing. And as you can imagine, with now four competitors in the bladder setting, in a relatively limited patient population, I think basically what I’m saying is I think that that split will change over time. We’ll have a higher degree of sales in lung versus bladder on a percentage basis.
Next question is from Steve Scala from Cowen. Please go ahead.
Thank you. A couple of questions. We have seen the resilience of brand Remicade despite biosimilar competition. Would you encourage us to use this as a guide in thinking about the future of Roche biologics in the U.S., or would you not encourage us to do so? And then, the second question is on HAVEN 3. The study had a primary completion in September. I’m just wondering if the data is in-house at Roche and what is your level of confidence that ACE910 will be a significant player in the non-inhibitor population? Thank you. Daniel O’Day: Hey, thanks Steve. Good to hear your voice. On the precedent [ph] if you like or the potential modeling that you might do on biosimilars, I mean, first of all, what I would say is that it’s really difficult, I mean we still have -- it’s still very early days, as you know, in the United States in terms of getting a handle on how the biosimilars are going to be uptake there, and I think it’s also a bit further off for us in terms of impact on our brands. So, the best experience we have is in Europe right now. And I would say that -- what I encourage you or discourage you, I would just say that it’s progressing as we would expect in Europe at this stage, let me say that. And I also think that the ability for us to make sure that we’re reacting and responding in the market so that physicians and patients have choice for the original brand will continue. And the other thing I would say to add a little color to that is that we’re finding in the very early days of Europe and I would expect that this is going to be similar in the United States as well with Rituxan, is that the subcutaneous has a preferential effect, if you like, in the biosimilar process. So, I think that that speaks for one level of defense, as we go into the Herceptin erosion too because as you know we have quite a high market share in Europe of Herceptin subcutaneous. But just to be clear, we have no illusions that -- yes that we can stop the decline here. But, we clearly will do everything possible to have that brand preference. And again, I’d just point out that it’s extremely important that our successor brands continue to perform well. So, Perjeta, Gazyva, Tecentriq and others need to continue to perform well in oncology and of course our brands outside of oncology. And then, I would just say on HAVEN 3, no, we certainly do not have an in-house. I assure you that when we know the data, you’ll know it shortly thereafter according to our exchange rules roles and we’ll get that out to you. If you ask me about my sentiment, I mean, I feel very encouraged. I mean, I feel very encouraged by what we saw in the early data in the non-inhibitor population. I don’t have insight into the trial or study. But, I remain very optimistic that emicizumab will play a very important role in the non-inhibitor population and we will see that data in the coming months, before the end of the year.
The next question is from Tim Anderson from Bernstein. Please go ahead.
Thank you. A couple of questions. Going back to IMpower150, it’s become a consensus view that the Company is steadily backing away from and deemphasizing this particular trial, which many are reading as a result either being negative or underwhelming. And I am wondering, if you might clarify your current position on this trial and its likelihood of success. And if you would say that this perception is wrong, and is this first trial riskier than the others in your program? Second question, going back to HAVEN 3, it’s also become consensus that in recent conversations you’ve been positioning this product as very much going after the non-inhibitor population, which is true, which speak to what you think results will be but also where you think pricing might come out. And I am wondering if you can just talk about how you are viewing going after both the non-inhibitor and inhibitor part of the market, and specifically will you be making a very aggressive push into the non-inhibitor portion? Daniel O’Day: Thanks, Tim. So, back to the IMpower150, I mean, let me just equivocally state that if it sounds like we’re pulling back, that certainly isn’t the impression you should get. We don’t have any more insights on the data today than we did six months ago. We believe in our overall strategy, which includes more than IMpower150, I just want to be very clear on that, always has. So, there’s nothing -- no change to that. But, I just would take a minute to make sure that everybody understands the way we think about the strategy. We think of it in multiple phases. The wave one was to be fast follower to the early entrants in the monotherapy and a couple of key indications, bladder and lung. And I think we have nothing to apologize for our data there and I think it’s strong, but clearly smaller indications and we weren’t first. Wave two is really about adding Tecentriq on the current standards of care in the respective earlier line treatments. And I think we have put a very comprehensive program into place. I mean, I realize that relative to the competition, we haven’t had any readouts in the past 6 to 12 to 18 months. That’s going to change now moving forward for the next several quarters and into the next year as we have a lot of readouts. And those readouts are our wave two strategy, which is Tecentriq on top of standard of care, because we believe that there is scientific hypothesis why adding Tecentriq makes a lot of sense could be synergistic, could be additive, we may be seeing immunotherapy type synergistic effects with either chemo or with Avastin. So, it’s a very thoughtful program and yet we have to wait for science to readout, right, because we placed a number of bets here that we are think are all good, logical, scientifically based bets. But, because we are still new in the field of -- we all, I mean we as an industry are still learning in cancer immunotherapy, we don’t exactly know which is going to read out. So, I’ll just remind you, we have got just in the lung cancer setting alone, in non-squamous, we have three different trials and they discriminate from themselves by the different types of chemo backbones with steroids and with Avastin. And then, we have a squamous and a small cell lung that also build upon a chemo steroid backbone. And then, we are looking obviously outside of lung at renal, triple negative in breast, where we’re either adding on top of or looking at the different types of combination approaches. So, I know it’s a little bit of a long answer to your question, but I want to give you a sense that there is no increased hesitation, we have no insight into IMpower150 data. And to your question, is it riskier than any of the other trials, the answer is, we don’t know. I mean, we don’t know, because we don’t know if there is an effect with one chemo background versus another, or with or without Avastin, but we are going to find that out. I mean, we’re all going together find that out in the next two or three quarters. And I would say, I think our program discriminates a bit from the competition and that each of our trial looks at different chemo backbones, as designed into the protocol. So, it’s not a dealer’s choice chemo backbone, where are you not sure if you’re going to be able to discriminate between the chemo backbone. You’re going to have very clear information of Tecentriq with a particular chemo backbone with and without Avastin and with and without steroids that will I think eliminate not just us but the field. So, we remain committed to the program and that’s all I can say now. And soon as we get the data, we will let you know. On HAVEN 3, yes, I mean, my confidence remains based upon the early data, based upon the really strong effect in the inhibitor population that I remain bullish on that. And in terms of our strategy, it is very much to look at the entirety of the hemophilia market, right, and that includes pricing, it includes other things as well, but it certainly includes pricing. We want pricing to be set at a level that allows patients in both the inhibitor and non-inhibitor setting to be able to access to our medicine and realize the benefit certainly we see in the inhibitor and certainly helpful in the non-inhibitor as well. So, I won’t go into more insight about that but clearly you’ll know our pricing strategy as soon as we get an approval in the U.S., and you’ll know the non-inhibitor data as soon as that reads out. So, we’re looking forward to both of those coming in the months to come. Hopefully that helps a little bit too.
Next question is from Vincent Meunier from Morgan Stanley. Please go ahead.
Hello, thank you for taking my questions. The first one is for the work on IMpower150. So, should we understand that IMpower130 and 132 with Abraxane and Alimta are probably more relevant in the competitive landscape in order to differentiate Tecentriq? And the related question is Avastin is only in 150, it is not in 130 and 132. So, if the Avastin arm read outs positively in 150, what can you do; what are your options? Because maybe it’s a missed opportunity not to have Avastin in the two trials 30, 32. Other question on the biosimilars, can you tell us what are the trends in terms of pricing in Europe so far, and in the coming quarters? And the last question is on Ocrevus. Are you expecting any change in terms of pricing or reimbursements, market access because of the generics of Copaxone? Thank you. Daniel O’Day: Okay, thanks Vincent. I don’t know if I’ll be able to add too much more than the answer I gave on IMpower150. I would just say that -- to your question on which one is relevant, I think they’re all relevant. And of course it depends on how the readouts occur. I would say that from a competitive standpoint, as far as our knowledge is concerned, I mean, we’re the only ones in a late stage large trial looking at the VEGF hypothesis. And so, if that works, I think we have a little bit of distance us between and the competition in terms of being able to generate data on a VEGF combination and a really robust trial. But so, I -- let’s see how that works. I have -- so they’re all relevant depending on how they read out. And I think there is -- nobody knows what chemo backbone might be. I mean, I know there’s some assumptions out there but nobody knows what chemo backbone could be, the most powerful. And data will win out here. So, I think the important thing is I think we have placed a broad enough number of bets that we have a good chance of winning on one of these bets, just not sure which one at this stage. And right, right -- so, hopefully that helps a little bit. On the biosimilars, I would say that -- yes, as you can imagine, it’s highly competitively sensitive, the pricing topics, I’m not going to give you details on that. I mean, you could probably ask some of the biosimilar manufacturers for their information, if they would like to expose it. But I would say, the following is that -- we think there’s value to the originator product. We think there’s value to our subcutaneous formulations that’s proving right in the market as well. And it’s again very much in line with what we expected. And we are in a good position I think to be able to respond to that with the complete understanding that we’re going to have significant erosion with MabThera. And I’d just point out that with MabThera we have two competitors in the market in Europe. The next competitor we expect to come in MabThera would only be beginning of 2019. So, we will have two players in the market predominantly between now and the beginning of 2019. With Herceptin, we expect several competitors to come on, starting the early part of next year. And Herceptin may have some slightly different dynamics than Rituxan as well. And the last thing I would say is even if I -- even though I was open to providing you pricing, it is so different country-to-country, it varies so much in terms of how the tenders are working, whether they’re regional tenders or national tenders that if there’s one thing that’s true about this is that it’s heterogeneous, it’s not homogeneous. And then, finally, on Ocrevus, no, I feel very comfortable with our Ocrevus pricing in the United States. I think it was both responsible for patients and for the healthcare system. I don’t see any need to adjust that based upon any near-term issues. And we will obviously provide you with our EU pricing strategy after that approval as well, but for now, extremely comfortable. And I think the reason I am comfortable with it is because of the endorsement and acceptance beyond the clinic, clinician and the patient, but from a payer perspective, I mean this has really been well-endorsed and well-received by the payers in the U.S. In most cases, it is maximum of one step at it which is a very good thing in the MS markets. And that has not been a barrier, even though we are still waiting for the J code, which will come into early next year. So, it’s all moving extremely well. I think it was priced in a very responsible way in United States.
Next question is from Sachin Jain, Bank of America Merrill Lynch. Please go ahead.
Hi, Sachin Jain from Bank of America. A few questions, please. Firstly going back to ACE910 in inhibitor setting, just your perspective on whether you expect an FDA outcome or not. And I believe you have done 20-day [ph] questions from the EMA. Is there anything of surprise in there and do you remain comfortable with your proposed dosing algorithm for [indiscernible]? Secondly, a very high level question for Severin. In your interpreted comments, you mentioned you are cruising comfortable at mid single-digits. Do you remain comfortable that you can cruise at mid single-digits next year, i.e. do you believe your launch portfolio is enough to offset a full year of pricing erosion? And then, any high level color you can give on the margin mix impact of launch product portfolio growing versus this immediate loss of pricing erosion? And then, finally, a clarification question but down on to Tecentriq growth. Given the dynamics you talked about in second line lung and bladder, whether any new indications do you expect Tecentriq to continue to grow next year? Thank you. Dr. Severin Schwan: Okay. Hi, Sachin. This is Severin. Let me comment on your first question in terms of growth and profitability outlook for next year. I should say, first of all, as usual, we’ll give a more specific guidance at the beginning of next year. But, I think what -- two things which we have said in terms of -- let me start in terms of sales, is one that we feel confident in terms of how the launch of the new product develops and how we see the portfolio progressing. We feel confident that we can compensate for the decline due to biosimilars. But, the second thing which we also said is that we expect the biosimilars to enter which has just now happened in third quarter for MabThera. We expect this effect to increase, as we go forward, as the biosimilars roll out in additional countries in Europe. And of course we will have Herceptin to enter next year in Europe. So, the effect of the biosimilars naturally as we all would expect, will increase as we go forward, that’s in our logic thing to happen and that of course will also have an effect on the growth. Now, the profitability, I have always said that of course, this is how shall I put it, that that puts tension on the system because on the one hand we have biosimilars entering, which means that we have the price effect of high margin products, which of course effect the bottom line and at the same time the new products have to be supported, as we launch them. So, this gives a natural tension in the system and we are managing that and we are working against that, kind of dynamics if you like. We are of course looking of where we can increase productivity across the whole value chain. But, in terms of where we land for 2018, I have to defer you for the year-end and the guidance which we will give at that time. Daniel O’Day: Yes, and Sachin on my side, so what I can say is that for emicizumab ACE 910 that the reviews are going well. There is nothing untold or unexpected happening. At this stage, there has been no discussion of it adcom. And we are working very, very collaboratively with the agencies. I think they recognize obviously with ACE 910 with the priority review in the United States, they recognize that there is a significant patient need out there and they, they are encouraged and they have encouraged us to look for as fast of a review process but also a thorough review of process as we can. So, I remain -- there is nothing that’s surprising me in the review process. And on the Tecentriq growth, yes, I just remind you that we’ve just received the approval in Europe of course. I mean, a couple of things. Even though we have competition in bladder, we continue to have a very good profile in bladder and in lung, and in lung also with the unequivocal data across different PD-L1 statuses and other types of comorbidities. So good data there. We’re going to continue to make headway in those indications, and we will have Europe coming on board, right. So, we will have the initial launches in Europe where we can launch immediately. And we will also have as the reimbursements come on next year, we will be able to launch in more and more countries in Europe. So, I do expect Tecentriq to continue to grow. Of course depending on the readouts that we have over the coming quarters, and the strength of that data, I think that also could have an impact upon the growth rate and guidelines and other things, but all of that we have to wait and see how the data reads out.
Next question is from Matthew Weston, Credit Suisse. Please go ahead.
Thank you very much. Two questions, if I can. The first is on Ocrevus in Europe. The CHMP agendas for the last two meetings have suggested that Ocrevus was going to be discussed, but obviously we saw no feedback. Can you just walk us through what gives you confidence that we will see a CHMP positive opinion by the end of the year? And then, secondly, a slightly philosophical question, as you prepare for the ACE 910 commercialization, cause I’m sure it’s crossed your mind. You decided a number of years ago to not enter the U.S. market with subcu Herceptin or Rituxan because at the time you were mindful of the significant financial incentives that doctors received under the AFP Plus reimbursement regimen. Why are you confident that the dynamic is going to be different in hematology where doctors rely on AFP Plus on both factor VIII and particularly on bypass agents for a very substantial portion of their personal income? Daniel O’Day: Thanks, Matthew. On the first one, what I would say is that this is, as you know and also as we’ve talked about before, the Ocrevus file is a very comprehensive file. It’s a very large file, it has RMS, it has PPMS, it has some of the largest number of data points that we’ve ever submitted to regulatory authorities. And we’re having good dialogues with the regulatory authorities, and because of those good dialogues that’s why I state with my opinion that we will get a positive opinion before the end of the year. It’s certainly the way that I’m interpreting the situation at this stage, but having said that, we’ve got -- we have to get that but I’m very encouraged by where we are in the process and by the discussions that we’re having. In terms of ACE 910, yes, point out a couple of things here. I mean, maybe a couple of things on -- just to answer your question on subcutaneous in the United States with Rituxan and Herceptin. There is this threshold between physician reimbursement for administration fees and overall benefit to patients and overall benefit to practice. Now what happened by the way, just to put it into complete context with Rituxan, two things happened. Number one, some of the reimbursement rates for the second hour and beyond infusions adjusted over the course of our thought process, to suggest that in fact with a much shorter induction time -- so, the first hour is obviously the most lucrative hour for physicians and then the second and third hour becomes less lucrative in the United States. And so there’s a real benefit in fact, if you can reduce the infusion time to a subcu and get it down to a period of time where you can actually process a number of patients, probably potentially more than one or two in an hour. If you can imagine, you can do the math. So that changed a bit and also the regulatory openness to being able to do a bridging strategy with Rituxan and Herceptin has also changed and adjusted. So that’s what led us to looking at Rituxan. And I have to say, I think it’s off to a very good start in the U.S., again because the benefit it brings overall to the system. And we’ll be looking as well at Herceptin, and as you know from the last half year the Perjeta and also the Perjeta Herceptin combination for a subcu. So that will continue. So that’s one thing that I would say. And back to the philosophical approach with ACE 910, again, we recognize there are different incentives in the hemophilia market today. But, those incentives will only hold up in the absence of a potential change in the standard of care. In other words, when there are opportunities to significantly affect the disease in a positive way and move patients, for instance from on -- more patients from on demand to prophylaxis, higher quality of life, I mean these things are very, very powerful with patient groups, with patients and frankly with physicians. So, I feel that at the end of the day, clinical profile trumps any other incentives in the system. And I think I am not going to give you more than that at this stage because we’re looking at different ways and different methodologies for approaching to market, competitively don’t want to disclose at this stage. But, we are well aware of the circumstances that you outlined. And we remain confident that given the clinical profile of this product that we can price it, get it reimbursed in a way that’s advantageous to everybody that’s in the system.
The next question is from Sam Fazeli from Bloomberg. Please go ahead.
Thank you very much for taking my question. I have three, if I may, one, very quick. Can you quantify the bolus impact on Ocrevus in the quarter? Is that possible for you to do? And then, the other one is on the PD-L1 test, unfortunately couldn’t be at World Lung but I understand that the Blueprint 2 data was presented. And based on what I heard at ESMO, there was some hope that possibly the Roche test will hopefully look the same in terms of the sensitivity as the other antibody tests. And I just wonder whether you have any update on that. And if it didn’t, how do you see sticking into the direction that I understood people wanted to go, which is to have one universal test that pathologists can use in different hospitals and not necessarily rely on different tests for different trials? And lastly, back to margins and profitability, not necessarily on a 2018 timeframe but looking at 2018 to 2020, 2021, 2022 timeframe, it seems like consensus is not expecting any margin evolution within their numbers. Could you just comment on what levers you have to potentially change that and maybe get some leverage out of the P&L, where that leverage might come, is it in R&D place? I know Severin referred to some productivity measures. But where can that come from? Thank you. Dr. Severin Schwan: Well, I can take the more general question first. So, the transition we are entering in terms of the biosimilar entry, on the one hand and the launch and the rollout of our new medicines obviously will go beyond 2018. I would say, this is probably taking about three years until we get back to a more, how shall I say, regular pattern in terms of patent expiries on the one hand and new product launches on the other hand. In terms of profitability and how margins develop, from -- because you asked longer term here, I mean, for me at the end it comes all down to how does the product pipeline develop. This is the number one barrier here. If we are successful in forecasting our pipeline and eventually launching new differentiated medicines, which really move the standard-of-care, then we will be able to ask a premium price for those, and that is always an opportunity to have leverage on the bottom line. If on the other hand, we do not achieve that, then aver time, you run out of business all together. So, this is the number one criteria; this is the backbone of our success for the future. And that’s what our strategy is about, earning cutting edge into innovation, progressing our product pipeline. But next to that, we have to work on the efficiency of our entire value chain and that goes really from research over development. We did a lot in manufacturing. Actually you can imagine as we move into new therapeutic areas, as we have this transition in our portfolio, we will have a lot of adaptation on the commercial side. And of course, it also affects all the support functions. I would say, one very important element here, if we talk longer term is the digitization, which is happening in healthcare, which I believe provides us with opportunities to move the standard of care due to insights we have in real world outcome data, for example. So, it helps a lot on the innovation front, primarily I would say, even but it also of course offers opportunity to be more efficient in the process, to do research and clinical trials, to do manufacturing, to do our commercial activities in a more efficient way. So, I think as we go forward, that is certainly also an important leverage to trigger. And again, at the end, it’s all pipeline. And with this, over to you, Dan. Daniel O’Day: Yes. So, thanks for the question. I mean, I think your question on diagnostics is clearly -- it’s a moving field right now and diagnostics and immunotherapy to begin with. And the vast majority of indication so far actually -- in fact it’s difficult to discriminate patients with the current test. Now there is most labels are all commerce [ph] labels. In fact, most of our trials that we have coming up with the chemo combos would be looking predominantly at all commerce labels as well. Having said that -- so, I guess my first point is, you need a utility for the tests and that’s still evolving. Having said that, you rightly point out the additional analysis and the blueprint, which is probably too complex to go into in detail here, but I would just say that four tests were looked at in the Blueprint 2. It is true that and Ventana, our diagnostics experts have multiple PD-L1 tests. The one that we’re using predominantly in our trial right now is SP142; they are different antibodies. And on first glance, it does seem that SP142 has more differences and similarities between the other three tests. But you also have to remember that we are looking at SP142 at both tumor expression as well as immune expression, and that may or may not be meaningful as we go into these earlier stage programs and processes. So, what I see happening in the field with us and with other companies is first of all, there is a desire to harmonize more on a single PD-L1 test or at least have data within your programs that allow you to compare between multiple tests, the more and more prominent test. And then, beyond the IHG PD-L1, I really see the field moving towards, as I said before, different types of even more specific tests, whether that’s RNAC [ph] tests like IgE or whether that’s GNA-2 [ph] and mutation burn tests. And we and the competition are looking at these types of analyses, generally post talk in their trials. But, I think we’re going to see that as we get in different line settings, there’s going to be, not just a harmonization on PD-L1 that’s going to be important, there’s going to be a necessity to look much, much more deeply into the diagnostic characteristics of a patient’s particular tumor type, to determine how to triage to different treatment courses over the course of their therapies. So, this is an exciting space, it’s an evolving space but it’s much, much broader than is there one PD-L1 test that’s going to be the right one to determine treatment and therapy choice.
Next question is from Andrew Baum from Citi. Please go ahead.
Couple of questions, please. Firstly on Esbriet. Could you tell us how many patients are getting Esbriet under your patient assistance program [technical difficulty] thinking about [technical difficulty] charitable foundation, and how that could be impacting [technical difficulty]. Second on Lucentis. Could you just outline the contractual relationship that you have with Novartis, given their impending or their anticipated RTH launch, [ph] sometime in 2018, given potential conflict? And then, finally, on ACE 910, could you just give us some background on the current dynamics of factor VIII, how much is currently [indiscernible]and therefore under PDM control and the extent to which that’s growing, just thinking about the various motivations in a different segment? Many thanks. Daniel O’Day: Thanks, Andrew. I apologize, I forgot to answer the previous question which was can I quantify the bolus to Ocrevus. No, I can’t. Sorry, that’s a quick answer but it’s predominantly in PPMS. No, no, I know this was from the previous question. I just recognized that I didn’t answer that question. So, apologies. Now back to Esbriet and Andrew on your questions, on Esbriet, no, I mean, we have a patient assistance program. But predominantly, what we’re seeing is that patients, if they go on to the patient assisted program, eventually are supported and aided to go on to support from their insurer, the vast majority go under support from their insurers. So, we have this so called conversion to paid strategy where initially people may be on the patient assistance program and then over time they’re supported relative to insurance. Of course, there’s a percentage of truly indigent patients that we cover but that percentage is not in any way, drastically different than what we see with the entirety of our portfolio. So, I can’t quantify for you specifically but there’s nothing -- there’s no dynamic there, if you are asking if there’s a dynamic that is somehow different or alarming than our other medicines. I would say, that’s not the case. Let me just jump to ACE 910. I actually don’t know the answer to your question on the current factor with -- the dynamic with factor VIII relative to PDMs. I’m sure that’s something we can follow up with or probably even a better question for the factor VIII manufacturers, to be honest with you. So, I don’t have an answer to that as well. And then, I’m just looking at my colleagues and what we disclosed with Lucentis. At this stage, obviously Novartis has the right to Lucentis. Andrew, are you asking if there’s a conclusion to that agreement, are you asking of other medicines or compounds come into that agreement?
No, I mean, when we saw Novartis recently, they are not -- they are talking about launching RTH [ph] in a way that sounds like they’re still bound [ph] kind of contractual agreement by building separate sales forces. And obviously there is an inherent contract there -- conflict there in Europe given the licensing from you. So, I am just wondering are you comfortable with this dynamic or does it require some kind of resolution? Dr. Severin Schwan: Yes. Maybe Andrew, I can shortly talk about this one. We are aware that we have released the Phase 3 data, we saw the 57% and 52%, which maintained two 12-week [ph] intervals. Actually for your information, it is the same for Lucentis; I didn’t see a huge difference. But, what we are focusing at the momentum is as Dan has said on the bispecific as well as on the port delivery. And on the specific situation actually for Novartis, we really don’t want to comment on specifically.
Next question is from Richard Vosser, JP Morgan. Please go ahead.
Hi, thanks for taking my questions. The first question is a follow-up on Ocrevus. And given your conversations with doctors in Europe, are you expecting a similar sort of demand curve or uptake for Ocrevus in Europe, once it’s approved? And then, the second question, just thinking about the APHINITY trial and Perjeta getting approved early next year, just how would you expect the guidelines to change with respect to that? And would you expect those to change shortly after the approval in January? Thanks very much. Daniel O’Day: Thanks a lot. So, I think it will vary from country-to-country in Europe. As we all know, I mean, Europe is very heterogeneous. You get Europe -- I mean, Germany out the door quickly but many other countries will have of course the reimbursement process to go through. And during that reimbursement process there is different types of factors that can influence the uptake rate. So, I really can’t comment or compare and contrast that to the United States because it would be just too difficult given the heterogeneity in the number of countries. I would say though, I mean just stepping back from the uptake curve is that this is a global community, the MS community. I mean we’ve had very good discussions across physicians from multiple countries around the world at ACTRIMS and other events. And I think from the standpoint of benefits, patient benefits, health system benefits, I mean, here, I think there is a universal opinion of it. So, I think probably what would be better is to look at the uptake of new MS medicines in these different countries that have launched in the past versus how they have launched in the U.S. I wouldn’t expect necessarily a grossly different dynamic there because I think the same type of restrictions that may have existed for other MS therapies could apply to Ocrevus and the uptake as well. Although, as we have seen in the United States, there is very few restrictions that have been placed on Ocrevus. So, that’s about as much color I can give you on that. On the APHINITY, yes, I mean, well, first of all, we are focused on the approval. And as we all know, the frequency with which NCCN and other guidelines organizations meet is not always the same. So, it will have to do I think both with the regulatory process, but also with when those guideline bodies meet and when they decide to publish the event. Having said that, I mean, I do feel strongly that the priority review in the United States is a very good signal, for how third parties see this data, and I will leave it at that.
Next question come is from Philippe Lanone from Natixis. Please go ahead.
So, gentlemen, thank you for taking my questions. Quick one on the impact of biosimilars on MabThera in Europe. You mentioned the preference for subcu. But could you just specifically say whether the minus 16% is only on the IV form or vastly or the vast majority of it on the IV form or is the subcu from is also impacted, as far as you see it, I mean in terms of your sales declining? The second question maybe is on diagnostics. We have seen that diabetes care is costing about 2% of growth for a number of quarters, and maybe number of years. I wondered whether there was -- you could make a good general comment on whether it’s business strategic or synergies for the rest of the diagnostic business? Daniel O’Day: Good. So, just quickly on the biosimilar, happy to give you a little bit more color. That minus 16% in the quarter, two-thirds of it, we believe is due to biosimilar erosion. And of that biosimilar erosion, it’s about 50% price and 50% volume. That gives you a little bit more color. The other third of the 16% is what I would call kind of a normal price decreases that you see across Europe. I think we had a slight decline in Poland and in France for instance, in the third quarter. So, I hope that gives you a little bit of a sense for it. So far the subcutaneous I think has been holding up quite well. And in many cases, the IV and subcutaneous tenders have been so far separate in some of the markets as well. So that’s as much color as I can give you to-date. And obviously as we have more experience in the coming quarters, I’ll do my best to give you a little bit more information on that. And Roland...
Yes. Thank you for the question on diabetes. I think in the appendix, we also have the portfolio results broken for down diabetes care. So, what you can see there is a certain volatility, pretty big swing that has largely get to do with the U.S. and the reimbursement cuts made in the U.S. and then year-over-year comparisons and then of course how these cuts actually been influenced and also the private pay sector. So, obviously, last year, we had another 20% reimbursement cut in the U.S. in diabetes and we are seeing some of these effects now spilling over into the private sector in the U.S. So that holds true for the traditional blood glucose monitoring. There is opportunities going forward in sensors, continues monitoring and pumps and also very much so in the entire holistic management of diabetes patients and that’s something that we want to focus on. There is some synergies on the analytics, of course. But, when you think about the business model, it’s a very separate business model, because here we’re largely selling either to wholesalers or to patients, whereas in the clinical laboratory space we obviously sell to large hospital networks, hospitals or commercial laboratories.
The last question is from Keyur Parekh, Goldman Sachs. Please go ahead.
Good afternoon. I have two questions, please. The first one for you, Severin. And going back to the comments you were making to Sachin’s question on kind of coasting nicely around the mid single-digit range from a growth perspective. Neither the Roche stock price, nor the Roche valuation seems to reflect your base confidence in the business. What do you think you as CEO of Roche can do to convince the market that your outlook is better than the credit you are given for today? And secondly, along similar lines for Dan, there’s a growing perception that Tecentriq is kind of the gulf between Tecentriq versus Opdivo or Keytruda is widening as time goes by, and the two competitive products seems to be adding a bunch of various indications and we keep waiting for Tecentriq studies to read out. Do you think that’s a fair perception? If not, what do you think it’s going to take to change that perception? Thank you. Dr. Severin Schwan: Okay. Let me just comment again on mid single digit growth. What I was -- just to be very clear, what I was referring to is that we are on a good track to -- fully on track, in fact to achieve our full year guidance, which as you know, we have slightly raised at half year to mid single digit growth. And this is what I was referring to. So, we have seen again in the third quarter a mid-single-digit growth, which confirms that we are on track to achieve mid-single-digit growth for the full year. So that is what I was speaking about and nothing else. Now, again, as we look forward into 2018, on the one hand, we have the positive dynamics to continue from the new product launches. As Dan has highlighted, we are confident for hemophilia, [ph] but we will also have to see the data in particular for the non-inhibitor segment. And there’s a lot to read out on the cancer immunotherapy front. So, good dynamics but at the same time of course a certain ambiguity and uncertainty around a number of sites still to be read out, which is inherent in our business of course. But on the other hand, of course, we will see more of an effect from biosimilars. Again, we just saw the first biosimilars entering in the first countries in Europe. So, without any doubt, the effect which we will see for MabThera will be more pronounced in the fourth quarter. Anything else would be unreasonable because the biosimilars are penetrating now for a full quarter and there will be additional countries that biosimilars enter for MabThera. So, this will also of course impact the growth dynamics for the fourth quarter. Having said that, we still confirm that overall for the full year, we will be in the mid-single-digit range. And as we go forward into 2018, again, to be very clear here, I am it’s obvious but let me state the obvious, we will have a full rollout of MabThera across Europe and we will have a number of competitors who come in for Herceptin. This is nothing new. We’ve been talking about that for a long time. It’s exactly as expected but now it’s going to come. Now, your more general question in terms of the share price and the confidence, now, what I am encouraged about is the uptake of the new products. I mean, remember what we -- how we looked at the business at the very beginning of this year and what’s the forecast for a medicine like Ocrevus, I think we all agree here on the telephone that it was considerably smaller than what we have seen now for the first six months. I mean, yes, the run rate already of a 1 billion for the year and that remember some estimates we had at the very beginning of the year which was very significantly slower. If you look at the growth rate now for the first nine months, 60% was driven by just Ocrevus, Tecentriq and Alecensa alone. And we have not even launched Ocrevus, Alecensa first line at least and Tecentriq outside of the United States. So, this is what gives me the confidence but I do not want to talk down the impact of the biosimilars, I mean, there is no question. The impact of the biosimilars will only increase over the coming quarters and then we will see out where we land net-net and we will provide the guidance at the beginning of next year. Daniel O’Day: Keyur, just to add to that, I mean, I completely support what Severin said. The Ocrevus is on a 12-month…. Dr. Severin Schwan: Sure, sorry. With run rate, I meant the annual run rate [multiple speakers]. Daniel O’Day: Yes. I thought somebody else might misinterpret that. But on to Tecentriq, so I guess a couple of things to frame it, and you and I have also been on this journey quite a bit. You see this time and time again in the industry but it’s magnified here. Any time that there is an uncertainty around how the science is going to develop, there is usually a rust [ph] to simplification. And I can recall and many of you us can recall on this phone call here how we’ve gone through different phases already in our immunotherapy knowledge and journey. I mean there was one point in time I remember being confronted many times the fact that the PD-1 was the answer to every single disease in every single patient. And unfortunately, I mean it is much more complex than that; really that is an option for some patients but it’s clearly not universal. So, what can we learn so far, and of course there’s different starting points for the competitors. But what we know is that we’ve seen many successes across the different PD-1s and PD-L1 but for every single one we’ve also seen trial shot unexpectedly different than we expected, right? Every single one of the agents out there has at least one trial. And I think that is an example of the fact that we are still learning. We are still learning in this area. I would say that the next three quarters for some very, very important disease states are going to be very instructive to all of us to determine to discriminate, to answer a number of questions. What’s the role of chemo combinations, what’s the role of Avastin, what’s the role of steroids across different disease states, and importantly, I think we’ll have a greater clarity on this question of is there a difference between PD-1 and PD-L1 because we will have more direct comparisons there. So, I go back to the three waves that we’ve had. We’re at the beginning of wave 2 with Roche. And Wave 3 is also just beginning. So, I also emphasize that -- I don’t emphasize that to show any lack of confidence in our ability to show good results in our Tecentriq trial that’s coming up, but we also have nine of the medicines that are in the clinic right now that we’re interrogating that treat the immunotherapy system different with cancer. And of course if I had -- If I could only pick one, I would say the bispecifics are something that are also quite intriguing to us and that we’re moving ahead in both solid tumors and in immunotherapy. So, this is going to be a very interesting time for all of us, I think; certainly I think it’s going to be a very exciting time for patients as these trials read out and as we understand better. But I would certainly not say that the gulf is widening to use your terms with Tecentriq versus other immunotherapy agents. And I think we have some really good studies that will help us understand better what role Tecentriq can and will play in the field of cancer care and particularly as you go into the earlier line setting. So, I want to close with that. And I think at this stage, we’ll thank you also for all your attention today as well. Dr. Severin Schwan: Thanks for joining.
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