Oct 18, 2018
Executives
Samir Shah – Global Head-Investor Relations Vas Narasimhan – Chief Executive Officer Harry Kirsch – Chief Financial Officer Paul Hudson – Chief Executive Officer-Novartis Pharmaceuticals John Tsai – Head-of GDD and Chief Medical Officer-Novartis Liz Barrett – Chief Executive Officer-Oncology David Endicott – Chief Executive Officer-Alcon
Analysts
Graham Parry – Bank of America Merrill Lynch Andrew Baum – Citigroup Matthew Weston – Credit Suisse Tim Anderson – Wolfe Research Richard Vosser – JPMorgan David Evans – Kepler Cheuvreux Florent Cespedes – Société Générale Steve Scala – Cowen Eric Le Berrigaud – Bryan Garnier
Samir Shah
Thank you very much and good morning, and good afternoon, everybody. Before we start, I just wanted to read to you the safe harbor statements.
The information presented today contains forward-looking statements that involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. Please refer to the company’s Form 20-F on file with U.S.
Securities and Exchange Commission for a description of some of these factors. In addition, I just wanted to point out that the information presented in respect to the proposed Endocyte transaction may be deemed to be solicitation material.
In connection with the proposed Endocyte transaction, Novartis and Endocyte intend to file relevant materials with the U.S. SEC.
We urge you to read these materials, including a proxy statement of Endocyte and all other relevant documents filed with the SEC when such documents become available and which will be available for free. The proposed Endocyte transaction has not been completed, and there can be no guarantee that the proposed Endocyte transaction will be completed or that it will be completed as currently proposed or at any particular time.
And with that, I’ll now hand the call to Vas.
Vas Narasimhan
Thank you, Samir, and thanks, everyone, for joining today’s conference call. We’re really pleased with our performance in quarter three where we continued our journey to be a leading focused medicines company powered by breakthrough innovation, data and digital technologies.
When you go to Slide 4, you can see that our group performance was strong, with sales growing 6% in constant currency, and core operating income up 9% in constant currency. Harry will go through the numbers in a bit more detail.
We’re also quite pleased with our innovation milestones in the quarter, and I’ll go through these in the upfront section, but with the AVXS-101 filing in U.S., Europe and Japan, BAF312 filed in U.S. and Europe, the approval of Kymriah in multiple geographies and the proposed acquisition of Endocyte, I think we’re also demonstrating we have the innovation power and the innovation momentum to continue to drive growth well into the future.
So if you go to Slide 5, when you look at the underlying drivers for that strong performance, you can see that Cosentyx and Entresto continue to perform well. I’ll go into each of those in a bit more detail, but I also wanted to point out our Oncology growth drivers are tracking extremely well, Promacta, Tafinlar and Mekinist as well as Jakavi.
And I’ll say a bit more about Lutathera. It’s become a real bright point for us as we now see there as a potential blockbuster medicine.
And I’ll show you a bit more data where we see Lutathera trending right now. Then when you move to the next slide, and you look at Cosentyx, I think as – we hopefully now shown it’s really established as the leading differentiator IL-17A inhibitor and had outstanding performance in the quarter.
You can see the 37% growth, really strong momentum by Paul and the team across all indications and geographies. Importantly, we surpassed Humira and TRx in the psoriatic arthritis in the United States.
And then we have a recent five-year data, which is similar to what we’ve shown in psoriasis showed that in TFA and NA showed sustained benefit complementing our long-term data, as I said, in psoriasis. I think that really built up the profile of Cosentyx as the leading IL-17A inhibitor on the one hand in psoriasis.
And then in rheumatology, really being unique in the mechanistic approach it has to treating the underlying joint disease that are really prominent in these two conditions. We go a little bit deeper on psoriasis on Slide 7.
You can see that we continue to gain market share in psoriasis in a very competitive market. I think Paul should say more about this.
There are a few reasons for this. One, we continue to believe that within the physician mindset and the payer mindset, there are two classes here thinking about in terms of the new drugs IL-17A and IL-12/23.
We are the leading IL-17A with some really important unique data sets, including we can treat multiple manifestations of psoriatic disease, including scalp, nails, palm, palmarplantar and joint involvement. And two thirds of patients have those additional sources of the disease.
And on top of that when you look at our real world evidence data sets we’ve been putting out into the community, they’ve consistently confirm the safety and efficacy benefits of Cosentyx. So we’re quite pleased and really looking for Cosentyx to continue its strong trajectory into the coming years.
Then moving to Slide 8, Entresto as well had a very strong performance in the quarter, doubling versus Q3 2017. You can see both U.S.
and ex-U.S. sales were nicely up.
I think importantly here we’re starting to roll out datasets from trials that we began in 2015 to really build up the profile of Entresto. Both TRANSITION and PIONEER taken together will probably hopefully enable us to really show that Entresto can be used in the hospital setting.
The TRANSITION study has already read out, and the PIONEER study will be something we’ll be presenting as a late breaker at AHA in November. That will enable us to ensure that patients are getting Entresto at the right time in the hospital.
In addition, the PARAGON study continues as planned following the interim analysis that we’d talked about earlier this year, with the results expected in mid-2019. I would also note that PARADISE study, which is in pre-heart failure post MI patients, is also enrolling according to plan.
So overall, the Entresto picture is looking strong, and we continue to see solid momentum around the world with this medicine. I mentioned Lutathera, and I wanted to show on Slide 9 the kind of really explosive performance we’re seeing now in Lutathera.
It’s off to a strong start in the U.S. You can see here number of doses per quarter, and this trend is really I think very encouraging.
And we’re now starting to roll out the medicine in Europe. In the U.S., we have 85 centers that are actively prescribing.
We have 70% coverage of the relevant lives. And in the U.K.
now, we have 18 centers actively prescribing. And I think, seeing the strength of the performance in Lutathera, feeling now that it’s a potential blockbuster medicine, seeing this outperform our deal case as part of the rationale when we come to the Endocyte deal for the confidence we had in taking the step to acquire Endocyte.
And I’ll talk more about that in a few slides. Now moving to Sandoz on Slide 10.
I think Sandoz continues to perform well in a difficult environment both in the U.S., but also around the world. When you look at Q3 2018 performance, the U.S.
impact continued of the industry wide pricing pressure, but we’re able to grow sales ex U.S. at 2% and importantly our biosimilars portfolio is growing at 21%.
And when you think about how we’re going to drive Sandoz moving forward, a lot of it is about executing a strategy of transformation and shifting the focus to complex generics and biosimilars. We’re well on our way to do that in the United States.
We announced that our planned sale of the core GX business to Aurobindo. And then we’re also expanding rapidly in biosimilars in Europe, and Richard can speak more about that.
But both Rixathon and Erelzi are performing well. We have the approval for our adalimumab biosimilar and our infliximab biosimilar.
And I would note that we are now in the market with our adalimumab biosimilars in four countries. And we have a positive CHMP opinion for pegfilgrastim, which should enable a launch, we hope, in Q4, assuming approval.
So overall, I think Sandoz is on the right track, challenging environment, but I think we’re taking the steps necessary to put the division in a place where it should be. And moving to Slide 11, Alcon continues its strong sales – sales growth, and I think that’s really the key point of the Alcon story.
We need to keep generating that strong sales growth across segment, and we did that in the quarter. You can see the 7% sales growth in Surgical, 3% sales growth in Vision Care.
Core operating income grew 1% and we’ve always known that the margin story for Alcon and this year was going to be a little bit choppy coming out of the trough 2017 margin. David Endicott is here and he can provide more perspective.
But when you look at the year-to-date performance in Alcon, we have core operating income growing at 14%, the core ROS at 18.6%. The business is on the right direction and is continuing its directory as we stated, and we remain confident, as Harry can discuss further, in the overall trajectory of the margins.
Now when you go to Slide 12, just to say a word within the quarter, we had a number of key data readouts and regulatory milestones. And I don’t want to go through all of these, but a few I wanted to highlight on this slide.
I will talk about AVX-101 and Endocyte specifically, but I did want to note that BAF312 was filed in SPMS in both the U.S. and Europe.
We will be presenting the BYL719 study results at the President’s presentation in ASCO over the weekend and we’ll be holding an investor call around that so everybody can understand better that data. Importantly, driving our in-line brand is really across the various brands, whether its Gilenya, Kisqali, Aimovig, [indiscernible].
We continue to generate data to support these important growth drivers of the company. Now before moving off to site, I wanted to give an update on ACZ885.
Yesterday, we have received a completed response letter from the FDA regarding the filing cardiovascular disease. As we have said last year, we were focused all along on trying to get the hsCRP responder group as a primary driver in the label, so that we could make sure the relevant patient population would get treated and there would be appropriate access to the medicine.
We have presented our case to the FDA. The FDA has asked additional questions, and has requested additional data with respect to the responder population and we’re evaluating now what will be the appropriate next steps.
I would want to highlight that we continue on track with our ACZ885 studies in lung cancer where we’re enrolling studies in adjuvant lung first-line metastatic lung and second line metastatic lung and we’re on track for readouts of those studies between 2020 and 2022. So moving to Slide 13, diving a bit more in AveXis.
There has been a lot of discussion I think given the competitive dynamics in SMA around AVXS-101. So I wanted to again level set everyone on the extraordinary results that you see in this medicine in SMA type 1.
I mean, whether you look at the videos that are posted by the NIH Director, or if you can look at other testimonials from patients, this is a simply extraordinary medicine where you have patients who would otherwise be expected to die, many of them out now beyond 40 years of age developing normally. So I think a few key points to highlight.
First, when you look at the baseline study characteristic, this was a severe population. And I think whenever you’re looking at results in SMA, it’s important to look at the baseline study population because there’s a lot of variability in the baseline characteristics of these patients.
When you look at the efficacy, we had a 100% of patient a live and without need for permanent ventilatory support. And if you can imagine a parent wanting to treat their infant, they’re certainly not going to want to take the risk that there is some percentage of patients that died with respect to the given therapy.
So we’re – we believe this is quite material and quite important when you look at treating infants for a devastating disease. We had nine out of ten achieve a CHOP-INTEND score of greater than 40 at eight months, 11 out of 12 greater than 50 during the 24 month study and 11 out of 12 achieving sitting unassisted during the 24 month study.
And when you look actually at the CHOP-INTEND scores, we’re getting patients in the relevant period of time where you can measure CHOP-INTEND into the high 50s or low 60s for their CHOP-INTEND scores. CHOP-INTEND is less relevant after the first year of life.
I think that shows you not only the efficacy benefit from a mortality standpoint, but also the functional benefit you get with these patients. Strong durability, we continue to achieve major milestones with this therapy out beyond four years for the patients we’ve been able to track two years in the reported data.
I think, again, I do want to highlight those patients who we’ve disclosed in previous conferences that are tracked for even longer than two years. Only a portion of them have received other therapies.
There’s also a portion that have received no other therapies and continue to do extremely well. When you think about that mechanistically, we know that motor neurons don’t divide.
You have your maximal motor neurons as an infant. When you receive a IV gene therapy, you would expect all of the – most of the motor neurons, we hope perhaps all of the motor neurons that have the appropriate gene inserted.
So the mechanistic rationale for waning of effect is not there in our view. Now there could be other things that happen as we do longer-term follow-up, but I think it’s important that you stick to the science and stick to the data when you’re looking at these kinds of medicine.
Lastly, I would point out on the right-hand side, when you look at the speed of response, speed of response is quite striking with respect to AVX-101 and other relevant therapies. I think that will be important for SMA Type 2/3.
And I’ll talk a little bit more about where we are in those studies in a moment. So moving to the next slide.
When you look at SMA type 1, we have successfully filed now in the U.S., Europe, Japan, all ahead of schedule for SMA Type 1 with AVXS-101. We have a potential approval, we believe, in the U.S.
in the first half of 2019. do have a breakthrough therapy designation there.
In the EU, we have – we believe the approval is mid-2019. We do have prime designation in the EU.
And we initiated submission in Japan in the mid-September. We anticipate the completion by year-end of the full file.
And again, we expect approval in the first half, given that we have a stocky jockey designation, one of the first medicines to receive this designation in Japan. So we’re quite pleased with the progress in SMA Type 1, truly transformational, foundational therapy for these patients.
Now on Slide 15, that will give you a little bit of an update about where we are on the trials because I know there have been some questions and some misinformation regarding this. When you look at where we are, the START study, which is a long-term follow-up for the SMA Type 1 patients, we have 12 patients enrolled.
When you look at the STR1VE study, which is a single IV dose confirmation study, patient enrollment is complete. When you look at the STR1VE EU study, we have six patients enrolled, and patients enrolling very well.
We expect to complete enrollment shortly. When you look at the SMA Type 2, Type 2/3 study with intrathecal dosing, patient enrollment is complete.
And when you look at the pre-symptomatic SMA studies, which are being conducted under the RUBRIC newborn screening, we have six patients enrolled, and we’re seeing very heavy demand for that study as well. So altogether, clinical program is on track to continue to expand beyond SMA 1 into 2, 3 and then eventually into the newborn screening.
So going to Slide 16, I want to say a word now about few slides about Endocyte, the acquisition we announced earlier today, which really builds on the earlier acquisition we’ve made with Advanced Accelerator Applications. As I’ve tried to articulate to all of you, we’re on a journey to focus our company as a medicines company.
And within being a medicines Company, along with our appropriate diversification and therapeutic area to build leadership in three platforms, which we believe are advanced therapy platforms that will drive differential growth. Cell therapy, we have Kymriah and then building beyond that, gene therapy, we’ve acquired AveXis and building on our portfolio there; and finally, in radiopharmaceuticals or radioligand therapy in this case.
Now when you look at the specific assets we have here in Endocyte, which we would plan to bring into our Advanced Accelerator operation, prostate cancer is expected to be an $11 billion market globally in 2024. This medicine is expected to provide an additional treatment option for prostate cancer.
And I’ll talk more about that because I think there is some misunderstanding in some of the notes I’ve seen over the course of today as to what exactly we’re treating here versus other therapies that are on the market. And this is the first-to-market potential product in our PSMA radioligand therapy.
The enrollment of Phase III has been initiated and is on track. FDA feedback, which we reviewed is very clear that radiographic BFF can be used as the endpoint, which should enable a relatively rapid, we believe, timeline for the Phase III study.
It’s a significantly derisked profile when you look at the paper that’s been published on the strong Phase II data. There’s extensive preclinical data as well as various other investigator-initiated data that we’ve reviewed, which gives us confidence in the overall profile of the medicine.
Now importantly, this expands our nuclear medicine platform following the launch of Lutathera, given the second radioligand therapy. It allows us to eventually move this PSMA 617 therapy into earlier lines of therapy.
And then we have opportunities to expand the platform in the future. One thing not noted in the slide is also would enable us to have a new manufacturing capabilities that we could then apply to our radioligand portfolio in the future.
So when you go to Slide 17, what exactly do we talk about here. And this is, I think, a very important point, and I hope investors will take a moment.
This is a therapy, as is the case with Lutathera, where we link a radioactive particle to a ligand. And this ligand has high specificity for a given tumor cell type.
And that way, we can target the radiation directly to the relevant cancer. So it’s a very targeted approach.
We do that with neuroendocrine tumors. And here, we do it with PSMA and prostate cancer.
The high-affinity targeting allows us to really manage – I think improve the efficacy and also manage the safety profile. Now other therapies available in the market are simply infusions of radium that are actually just used for bone metastases, not for metastatic prostate cancer.
So if you look at your benchmarks for what are the appropriate sales potential, please ensure you are using relevant benchmarks when you do this. Now once this is bound – the particles are bound together, they get internalized, then you would expect that the cancers then ultimately respond.
And that’s a response that we’ve seen. And when you look at the data on Slide 18, you can see here in the Phase II study, we had a strong PSA response, which we think is a relative measure.
You can see on the left-hand side, we had a solid trend in these patients, who have failed multiple lines of therapy in PFS, as well as an overall survival. And we’ve seen similar data from other smaller studies sets and IITs [ph] as well.
So when you go to the next slide you can see our – the Phase III VISION trial, which is currently enrolling, take the two-to-one randomization, take patients with metastatic prostate cancer, they have to have a positive PSMA scan and then have had a priority taxane or a prior novel androgen access drug. And after that, then they’re randomized into either the PSMA drug or the best supportive care, then we see.
We have 750 patients enrolled and initiated. And as I said, FDA has agreed to the endpoints on both primary and secondary.
So when you go to Slide 20, you can see that some of the deal characteristics. We’re certainly happy to answer any questions, but I think it’s relatively straightforward.
We fund it through cash. We don’t expect dilution with respect to this deal.
We expect it to start to contributing to group sales in 2021. Our overall financial expectations if the medicine has a blockbuster potential, and if we’re able to get into earlier lines of therapy, we can have even higher sales potential with this medicine, which would generate an attractive IRR to the company.
And of course, all of this is subject to the appropriate approvals from Endocyte shareholders and the relevant regulatory agencies. So if you go to Slide 21, expected next steps for the deal.
Of course, we’ll continue to generate the data and provide additional information as it becomes available. We have filed a proxy statement – we will file the proxy statement with the SEC, and we are hopeful to have closing in the first half of 2019, subject to the various considerations.
So moving to Slide 22, last slide before I turn it over to Harry. We are going to hold an R&D and investor update on November 5.
I will have a deep dive on AVXS-101. We’ll have some of the key scientists there.
So investors can speak to the team directly and where we are in that program. And then we’ll have a number of other detailed updates on the range of programs, a few that I would want to call out that are beyond what you – we traditionally talk about QAW039 or ZRTH2 antagonist for severe asthma where we may now start to move towards study readout.
We really want to make sure everyone understands we believe substantial potentials for this medicine. We’ll go through our multiple sclerosis portfolio of BAF racotumomab as well as the status with respect to Gilenya.
We’ll provide all the RTH258 two-year data and continue to demonstrate the profile of that medicine, as well as provide an update on the Oncology late-stage portfolio, building off of the BYL presentation we will make this weekend and provide an update to you early next week. So overall, I think a really strong performance.
And I’ll hand it over to Harry to give you some more perspective from a financial standpoint.
Harry Kirsch
Thank you, Vas. Good morning, good afternoon everyone.
So as usual, my comments refer to growth rates in constant currencies unless otherwise noted. So on Slide 24, you see the summary of our quarter three and year-to-date performance.
We continued to deliver good growth, with quarter three sales up plus 6% and year-to-date sales up plus 5%. This performance drove bottom line growth as well.
So core operating income was up 9% in the quarter and 7% year-to-date. As you can see, our free cash flow grew plus 10% the first nine months to US$8.8 billion, driven by this very strong operating performance.
Year-to-date operating income grew 3%. And it’s driven by the quarter three operating income declining 13% as we recognize charges for ongoing restructuring programs and the impairment of CyPass.
Turning to Slide 25. We see here the quarter three and year-to-date core margins of the group at each division.
Strong sales uptake in Innovative Medicines drove margin expansion for the division and the group. Innovative Medicines margin was up plus 2.1% points in the quarter, bringing year-to-date margin up 1.1% to 32.4% of sales.
Group margins improved by 0.8% points in the quarter and plus 0.5% points year-to-date, driving the margin to 27% of sales. Slide 26, I wanted to have a quick view on the Alcon sales and margin progression over the past few years based on September year-to-date numbers for each of the years.
As you can see, investments in 2016 and 2017 were necessary to stabilize and then grow again the top line. In 2018, the strong sales growth is driving margin expansion.
Year-to-date core margin improved by over 1 point to 18.6% of sales as compared to a – margin year in 2017. We have always said we expect some quarterly fluctuations in the margin for Alcon.
And David Endicott clearly can give you some further flavor on that. In quarter one 2018, the spending was lower.
And in quarter three 2018, Alcon increased investments behind some key brands. In quarter four, typically, margins are lower each year compared to the full year margin due to increases in equipment sales as hospitals finalize their purchases before year-end.
Hence, it’s always important to look at year-to-date and full year numbers. Clearly, we expect 2018 full year core margin to be up with the 2017 full year and then full year margin growth in each of the following years.
Importantly, mid to long-term, Alcon remains committed and on track to achieve margins in line with the medical devices industry, i.e., in the range of low to mid-20s. The margin expansion is expected to be driven by continued strong top line growth, improved gross margin and cost leverage.
On Slide 27, just back to the guidance. We are increasing our group sales guidance to grow mid-single-digit so at higher end of what we said before, given our year-to-date 5% sales growth.
And we expect that to continue at a nice level in quarter four. This is driven by strong performance of the Innovative Medicines division, where we also revised up full year guidance to grow in the mid to high single-digit range.
This guidance includes, also when you look at the core operating income, when we confirm our core operating income guidance as issued in January, expect it to grow in the range of mid to high single-digit. And as I mentioned earlier, also in the year, the guidance includes AveXis R&D and prelaunch investments.
And as you see, very consistent with our year-to-date performance, where we grew sales plus 5% and core operating income plus 7%. On Slide 28.
just a quick update on the expected currency impact, assuming mid-October rates would hold for the future. On full year of 2018, the currency impact is expected to be flat on both sales and core operating income.
As you can see here, the strengthening US dollar has a negative impact on half two, offsetting the positive impact we have seen in half one. Should currency stay at the current level throughout 2019, we see a negative effect of minus 2% on sales and minus 3% to minus 4% on core operating income for full year 2019 results.
This, as always, pay close attention to this as you build your models. And as most of you know, we are always updating the expected currency impact each month on our website.
And with that, I turn back to Vas.
Vas Narasimhan
Thank you, Thank you, Harry. So when you go to Slide 30, I think we have already told you we delivered strong accretive growth in the quarter and pleased with our momentum there and continue on track towards our goals with respect to margin expansion and top line growth.
The innovation momentum is continuing in the company. We progressed our advanced therapy platform strategy with the agreement to acquire Endocyte, and we are on track to deliver our full year guidance.
So with that, we can open up the line for questions.
Operator
[Operator Instructions] We have the first question in the line, is from the line of Graham Parry from Bank of America Merrill Lynch. Please go ahead, you’re now unmuted.
Graham Parry
Great, thanks for taking my question. So firstly, on the Cosentyx, could you give us an update on your contracting into 2019?
And have And have you seen less rebating needed to retain first-line positions? Or is Lumia in the prospects of Infliximab skewing that contracting at all?
Secondly, on your SMA franchise and could you just give us a best guess on timing of filing in type 2, 3? Can you file 2020 on the back of a strong data?
And also, WMS, there was some data on branaplam, we seem to show worse CHOP INTEND scores than we see with the Roche oral agent or AVXS-101, but there was dose reduction and discontinuation temporarily. So perhaps, you can help us understand how you think that data compares to the other agents in development and in the market and where it fits in your overall strategy going forward?
Third is biosimilar Rituxan. Could you explain when you expect to refile and why you haven’t refiled that yet?
And last one, just an update on Afinitor. Looking at court dockets, it looks like you settled most of the litigations and ITRs there.
Can we see some protection there beyond your prior March 2020 guidance? Thank you.
Vas Narasimhan
Thank you, Graham. So first on Cosentyx contracting, Paul?
Paul Hudson
Graham, thank you for the question. I mean, it’s too early to announce where we stand for 2019, but the conversations progressed as we would have hoped through the summer.
There is definitely a more instant dynamic for the – because significantly larger asset than we were at this time last year when we went into this, so we have more leverage. We’re also very pleased with we got picked up in volume in first line.
So we’ll be open-minded and [indiscernible] expect as we go into 2019, but I’m very comfortable with the outlook for us we transition into next year. So with respect to SMA, I was just quickly confirm that on AVX type 2 – 101 type 2 or 3 current stated buying objective is in 2020.
Now with respect to branaplam, LMI turn it over to John.
John Tsai
Yeah, I didn’t – can you repeat the question regarding LMI.
Vas Narasimhan
John, it was regarding our overall plan with respect to LMI in our portfolio.
John Tsai
Yeah, we continue to advance LMI according our original plans who look at exploring opportunities in terms of combinations with our AveXis 100. So our current plans are to continue to explore opportunities moving forward in this space.
Vas Narasimhan
I think on LMI, we had some early studies, I think we disclose that WMS we feel good about the overall profile, I would say that our hope is that gene therapy will be foundational. And I think the question of whether or not supplementation will be required at all is something that clinical trials will ultimately have to determine, but orals will certainly have a role for patients who have antibodies at baseline or patients who have maternal antibodies prior to being able to get the foundational gene therapy is how we sort of overall see this space evolving and with respect to biosimilar Rituxan, Richard?
Richard Francis
Thanks for the question. So obviously we’ve been working closely with the FDA and have discussions on a thought forward for rituximab.
We are currently awaiting with just to clarify the next steps once will have that we have that will come back to you and let you know.
Vas Narasimhan
And then finally, with respect to Afinitor. Liz?
Liz Barrett
No, sure. Afinitor and we do expect generic competition in Europe beginning to beginning of 2019 and then limited generic competition, the end of 2019 in the U.S.
And beyond that, we really just can’t any other information.
Graham Parry
Thank you, Liz.
Vas Narasimhan
Thanks, Graham. Next question.
Operator
Your next question comes from the line of Andrew Baum from Citigroup. Please go ahead.
Andrew Baum
Thank you. Couple of questions.
Given the appointment of a new chief legal counsel and given your focus on upgrading the standards which Novartis holds its compliance, I would imagine you’ll be seeking to close out the numerous ongoing investigations, particularly in the U.S. with the Secretary-General.
Can you give us some indications of what kind of timing we might in order to reaching closely and if there’s anything you feel you can have a feel on financial settlement I’d be interested that I understand maybe challenging. Second, in relation to Cigna, which is obviously lighter than I think the Street was looking for in the quarter, could you break down exactly why that was?
Was it discontinuation a function of the data? Was it increased rebating or prior authorization or other factors?
Thank you.
Vas Narasimhan
Thank you, Andrew. With respect to the first question, we’re pleased that we have – joining us Chief Assets and Risk Officer from deep expertise and managing global organizations and really elevating their capabilities on FX risk and compliance and of course we have Shannon Klinger, our Chief Legal Counsel as well now being elevated up on the team.
So I think overall we have the right team in place, now in terms of the various litigations around the world. I can’t provide I think any specific details.
But I would say, we’re looking to try to accelerate closing these matters so that we can move forward, given the new culture in the company, which is one that on the one hand, wants to be much more empowered and curious for our people and on the other hand wants to have an uncompromising approach with respect to integrity, ethics. And so I think once we have clarity on any of those matters, we’ll give you information.
But certainly, my aspiration is to try to close off these matters so that the company can move ahead in its new strategy and new direction. Now with respect to Cigna, Liz?
Liz Barrett
Actually there are several factors that contributed to Cigna declining. I think it’s really important for us to note that we actually had growth in markets except for the U.S.
and the emerging growth markets. Emerging growth markets really effacing.
So the majority of the decline is in the U. S.
There were three factors that contributed to that. One is actually there was a reduction in inventory.
So that was about half of the decline in the U.S. And then to your point, it was around the TFR.
I think the great news for patients that we delivered at ASCO and presented was around patient’s ability to come off drugs. And I think that’s something that both physicians and patients are excited about.
But as patients come off, we didn’t replenish the funnel at the same rate. And so we’ve seen some of that.
And then the third factor is really around competitive pressure in the market and what we’ve done. And I think the most important thing is, in reaction to that, we’ve – we’re really refining our messages to focus on efficacy, both in first line and in second line because we’ve also seen an increase in imatinib generic.
So we want to focus our message and those failures are beyond on that. And so I do think we felt like it will – the decline will stabilize, and we will return to growth in 2019.
So, it’s not something we expect to continue.
Vas Narasimhan
Thank you, Andrew. And next question please.
Operator
The next question comes from the line of Matthew Weston from Credit Suisse. Please go ahead.
Matthew Weston
Thank you very much. Three questions, if I can, please.
The first on AveXis launch dynamics. Clearly, you’ve set out the time line that points to the middle of next year.
Can you give us some comfort around the manufacturing supply that should be available at launch if you were to see three global approvals? And also, given expectations for launch timing because drugs sometimes go awry, can you give us your view as to how you see the rollout?
Is there a strong bolus that you expect very rapidly get rolled out? Obviously, something where reimbursement dynamics and really the first gene therapy out that means the uptake will be slower.
Secondly, on Votrient another drug in Oncology, where we saw a slowdown in 3Q. Liz, would be interested in whether there’s anything specific behind that dynamic.
And then finally, Vas, on Endocyte. The one thing that slightly surprised us, the deal structured as a merger rather than as a tender, which often suggests there are competition concerns.
And so it’s whether or not you’re prepared to comment, as to whether or not you expect competition commission scrutiny and whether that’s around that CAR-T platform or whether that’s around the Lutetium platform and how you see that playing out?
Vas Narasimhan
Great. Thanks, Matthew.
So first on AVXS-101 supply and then the global rollout, I’ll hand it to Paul. Paul?
Paul Hudson
Yes, it’s been a great pleasure to get to that AveXis team in more detail, and one of the real impressive things in science has been the commitment to world-class manufacturing on a significant scale. And as we get deeper into being credible partners of them, it’s quite clear that we can match with the IV and SMA 1 whatever the demand may be.
So we’re comfortable there. In terms of rollout, really, it will be – we’ve gone through the breakthroughs in all three jurisdictions, as Vas said.
As they go online, we’ll be there to match the demand. As for bolus, I think you mentioned, while there is a little bit of a bolus, I’m sure we again are ready to treat whatever presents are supported by physician and payer.
Vas Narasimhan
And I would note as well, as we get further along with AVXS, it’s important to note that on intrathecal dose is significantly lower than the IV dose and then supply considerations become much more – much less central. With respect to Votrient, Liz?
Liz Barrett
With respect to Votrient, we’re actually where we expected to be at this time. I think it’s important to note the dynamics what’s happening in RCC, particularly in the first-line treatment with the approval of the I/O, I/O in May as well as the impending data that’s coming at ESMO around the AO – I/O TKI data, so I think it’s fair to say that in the U.S.
and Europe we expect to continue to see some declines, which is exactly what we projected. And it’s also important to note that we are seeing very strong growth in Latin America, Japan and emerging growth markets and recently received reimbursement in China.
So we actually have some growth markets offsetting the decline that we are seeing in U.S. and Europe, but it is showing strong growth in other markets.
Vas Narasimhan
And then lastly with respect to Endocyte and the structure of the deal, Harry?
Harry Kirsch
Thank you, Matthew. So there are no specific concerns here.
Just the structure that both parties agreed upon to do a one-step merger versus a tender offer. So nothing specifically to read into that.
Vas Narasimhan
Okay. Next question.
Thank you, Matthew.
Operator
The next question comes from the line of Tim Anderson from Wolfe Research. Please go ahead.
Tim Anderson
Thank you. On Cosentyx second biggest right now competitive area, and you’ve got the J&J ECLIPSE trial close to report out fairly soon head to head versus your drug.
Can you talk about how J&J the sponsor for that trial may have optimized that trial to increase the odds that it hits and also your expectations on the odds that it will be positive [indiscernible] with the dose happen, what’s going to be Novartis’ talking points in defense of Cosentyx? And are you going to say it won’t have any real commercial impact on the product?
And then the second question, just to clarify on formulary positioning for Cosentyx, you guys kind of gotten beat up earlier in the year when you rebated – changed rebate structure on Cosentyx to try to get out of the rebated trap on first-line psoriasis. Has that had success in moving you up into first-line access?
And what do you expect on that particular front in terms of access restrictions in 2019?
Vas Narasimhan
Yes, I think both of those for ECLIPSE and then the formularies situation for Paul. Paul?
Paul Hudson
So thank you for asking the question. When you sit down with dermatologists in the clinic, clear is clear.
This debate about my posse is bigger than your posse is a little bit less relevant. Now it matters to patient outcome.
And of course, the study may readout, you’d expect a well-organized competitor to pick its moments to be able to make sure that they have some differentiation. Our confidence in not worrying too much about the outcome is because we think it will be mainly a campaign on marketing message.
Maybe it will allow – the data set may be able tell us more about them. More importantly, I think it’s worth evaluating the ARROW study, the more mechanistic study, that we have in play.
Because the real unanswered questions in dermatology are about the extra manifestations. I’m thinking one of our backup slides you can see on the event, that we care greatly about advancing the understanding – accelerating the understanding, and the understanding for the dermatology community.
And two-thirds of these patients have other complications where predominantly IL-17A is the driver. So you have to recognize that the real news will be ARROW.
Yes, there will be some marketing impact, I’m sure of ECLIPSE depending on how we reach out but we’re comfortable with that. As for the rebating and for looking – let’s look back, first, the last two years that we’ve said that we will be thoughtful about our rebates in Cosentyx and that we’ll trade access enough to grow volume faster than the additional rebate and run a successful business.
So that will be proven clearly that we’ve done that, and very pleased, by the way, with our Q3 performance. We don’t dig deeper and share data on the first-line setting, but it’s performed exactly as we hoped it would do.
And it’s sets very nicely for 2019, I said in –answer to a question earlier. I think from Graham that we got ourselves set up very nicely for 2019, but we haven’t advertised what we’ve achieved.
We are confident for the position and the strategies deployed in the last couple of years.
Vas Narasimhan
Thank you, Paul. Thanks Tim for the question.
Next question operator.
Operator
Next question comes from the line of Richard Vosser from JPMorgan. Please go ahead.
Richard Vosser
Hi, Rich Vosser, JPMorgan. Thanks for taking my questions.
Just a question on the Endocyte deal, first of all. Just – first of all, can you give us some help in terms of the proportion of prostate cancer patients express their PSMA operating on them?
And also, thinking about the initial indication that you’re doing the Phase III trial, and it looks like it might be post taxane. So does that mean you have to fail taxotere?
Just some thoughts on the positioning there. And perhaps you could give us an idea of whether the royalty payments still stand to AVX post the transaction, whether those stand.
And also on the manufacturing, you talked about that being important. Perhaps, you could update us and think about the capacity that it brings along with that.
And second area, just thinking about the CRL on generic Advair. Perhaps, you could update us there.
And final question on Alcon. You’ve hopefully given us a 2023 timeframe for margins in Alcon to hit the low to mid-20s.
But perhaps, you could give us an idea or the pace of that improvement in margins. Thanks very much.
Vas Narasimhan
Great. Thank you, Richard.
So first question on just the overall landscape for prostate cancer PSMA, Liz.
Liz Barrett
Sure. There’s about 70% to 80% of patients express PSMA.
To and answer your question directly, yes, in the trial we’ve shown, you do have to fail at least one taxane. Doesn’t have to be taxotere, but it has to be one taxane.
And I think our goal is in the future to move it earlier in the treatment paradigm, so we will begin to think about that post close. And as far as – I don’t think we’re commenting as far as the royalty is concerned at this point.
And then lastly, around the manufacturing, there’s different types of manufacturers. There’s direct and indirect, and the method that they have is really just give us the capability of being able to generate less waste and have a more purified therapy.
So we’re looking at how we leverage that technology and that expertise over to AAA. And I think, from that perspective, that sort of answers the question on what we think is the benefit of the manufacturing.
They are currently using a CRO, so I think our ability post close to look at the total manufacturing and see the best way forward, we’ll look at that post close.
Vas Narasimhan
And it’s certainly our aspiration to drive that synergy given the capability we have within AAA to reach patients eventually all around the world through our supply chain. Next the CRL on generic Advair, Richard Francis?
Richard Francis
Thanks for the question. So really to reiterate what we said in the previous earnings call we’ve had good discussions and communications with the FDA, we believe we understand what is necessary to get their generic Advair to the market.
And we stick with the time line as we communicated earlier where we see this coming to the market at the back end of next year.
Vas Narasimhan
Great. With respect to the pace of Alcon margin improvement, David?
David Endicott
The 2015 is – sorry, just starting with 2017, obviously, the trough year, 2018 will be up, 2019 will be up on that. We really haven’t commented on the pace, but we intend to have our Capital Markets Day in November.
And December, we’ll have an opportunity to take you through the margin progression, how we see that. But it obviously moves great deal on our products like our EDI, our manufacturing productivity and then leveraging our cost structure so we feel good about where we go a long-term.
Vas Narasimhan
Great. Thank you.
Thanks, Richard for the questions. Next question operator.
Operator
Next question comes from the line of David Evans from Kepler Cheuvreux. Please go ahead.
David Evans
Thanks very much for taking my questions. It’s David Evans from Kepler Cheuvreux.
Just on Lutathera, the initial launch, as you pointed out, had been excellent. It’s been faster than I think probably most people would’ve modeled.
Can you just please give us a little bit more of a view on the shape of the launch? How you expect that outlook?
Are there any kind of sticking points in terms of getting access to centers and training centers up? Or should we expect as a typical fast linear pharma oncology launch in the U.S.?
And equally, Europe, I would imagine should be a lot slower. Is that fair?
Thank you.
Vas Narasimhan
So Lutathera, Liz?
Liz Barrett
Yes, sure. I think you’ve said it appropriately.
I think we are seeing what you would normally see in traditional pharma launch. And I think that we were very pleasantly pleased with that.
We have over 85 centers in the United States, as Vas showed earlier. And then we expect that to continue.
We don’t – we would – I would say you could look at it like you would a traditional model. And I think in Europe, you’re correct, that we do expect a slower uptake at the centers.
It’s really important to note that it could take up to a year for a center to really understand and be prepared for this therapy. So I think the team is doing a phenomenal job.
We’re also just starting to see reimbursement in Europe. And so while we do expect it to be slower – slower than in the U.S.
So I think the majority of the revenue going forward in the next – over the next period will be – mainly be coming from the U.S., but we’re really pleased with the uptick so far.
Vas Narasimhan
And also Liz’s team is plan is to get this global over time as well. So next question operator.
Operator
Your next question comes from the line of Florent Cespedes from Société Générale. Please go ahead.
Florent Cespedes
Good afternoon gentlemen. Thank you very much for taking my questions.
Three quick ones. First, on Afinitor, could you give us more color on why the product decline in Q3 versus the slight growth in H1 due to the fact that we are approaching the end of its patent life?
Second question on canakinumab could you give us – share with us little bit more regarding the requirements from the FDA is there a new large outcome trial in calendar year for future of this product? Or could you provide the data, more information to the FDA based on the trial available so far?
And last question, for Richard and Sandoz, Europe looks a bit soft this quarter after a 7% growth in H1. There is only 1% growth in Q3.
Is there any reason beyond that? Thank you.
Vas Narasimhan
Thanks, Florent. Liz on Afinitor.
Liz Barrett
Afinitor is really driven by our CDK and our breast cancer market, so that’s what’s driving the performance there, as you see in the United States since the CDK market has actually penetrated more. We saw a leveling off of Afinitor.
But now you’re seeing the increase of penetration in CDK in Europe and other markets then you’re seeing subsequent decline in Afinitor, so we expect the same dynamic to likely happen as the CDK market begins to penetrate in earlier lines in those markets as well.
Vas Narasimhan
And then John with respect to the canakinumab CRL.
John Tsai
Yes. Regarding the canakinumab CRL, as we saw from the Sandoz [ph] trial, we knew that patients who achieved HSCRP less than two received the most benefit.
And as we continue we have discussions, and we received the CRL yesterday, and we’re continuing to explore additional information based on the information that we received from the FDA. And we’ll for have further understanding as we move forward.
Vas Narasimhan
Yes. So we’ll provide updates on that as we go.
And then Richard on the EU generics.
Richard Francis
Yes. Thanks for the question Florent.
So there was a softening of the performance in the European business, and let me start off outline what drove that. Firstly, it’s worth noting that we did by all launches that we had in quarter three last year.
So prior year was a pretty big year for us with the launches of [indiscernible] and then on the retail side, over that – so that will have an impact on us as well as some seasonal buying patterns, which are constantly varied across quarters and some years and so it doesn’t impact of that. So I remain confident about the European business has performed well and going forward obviously, we have a number of launches coming up in the near term.
This week, we launched Adalimumab into Europe and the number of markets, as Vas mentioned, as well as we are optimistic about coming to Europe in the European business pretty soon as well as in infliximabe. So I hope that answers your question, Florent.
Florent Cespedes
Great. Thank you very much.
Vas Narasimhan
Thank you, Florent. Next question operator.
Operator
The next question comes from the line of Steve Scala from Cowen. Please go ahead.
Steve Scala
Thank you. Several questions.
Kymriah in Follicular lymphoma, the filing has been delayed. The company previously have said manufacturing issues would not delay filings, is there a change in that?
Secondly, Paul, you previously have said thousands of Type 1 patients would want to AVXS-101 upon launch which implies multibillion in revenue in 2019, fueled by, as you have said previously time is neurons. The answer to Matthew’s question was a bit more muted than that positive portrayal in the past.
I’m wondering if you could amplify. And then lastly for Richard, biosimilar Humira in the EU.
What do you think the slope of adoption will be? Can biosimilars get 25% molecule share in the first year or more?
Thank you.
Vas Narasimhan
So I think first on Kymriah. Liz?
Liz Barrett
No. In Kymriah, we’re currently our manufacturing, we’ve just announced a slowdown on trials, but we have not noticed any ending of the trial or expecting that we will – that we would delay any trial because of the manufacturing.
So I think that’s the only thing we want to add at this point.
Vas Narasimhan
So in our aspiration is to keep FL as well as the other B-cell cancers on track with respect to Kymriah. Paul, on Type 1 SMA?
Paul Hudson
So Steven, sorry if I was somewhat mute there was my intention I was trying to respond to the manufacturing question which I’m comfortable with. The SMA community is just for gene therapy.
We do believe it’s going to be from foundational across all SMA types. Our first indication will be in newborns, and we expect to have a significant demand for that patient population.
And we will be ready to match that demand. I should perhaps mentioned earlier about our North Carolina manufacturing side that we made a big investment into triple our capacity.
So we’re preparing very well for whatever is there and we do hope that there was a significant number of patients as much for the patients as for the business.
Vas Narasimhan
Thank you, Paul. Biosimilar at Humira, Richard.
Richard Francis
Yes. Thanks for the question.
So to answer your question about what market share penetration there will be. I think it’s an interesting question, and what I would say if you look at it historically, every biosimilar comes to the market in Europe, I think changes the adoption and moves it outwards.
And we saw that obviously last year with rituximab coming to the market, and you see that penetration levels there. So – and we’ve also got obviously a few competitors coming to the market with this.
I think that drives me to be optimistic about the biosimilar penetration over the first year. Also stand with that.
I won’t get too specific about numbers, but I do fill the European markets ready for this and most definitely the health authorities need to be looking at opportunities to save money, so quite positive.
Vas Narasimhan
Thank you, Richard. Thanks, Steve.
Next question.
Operator
The next question comes from the line of Eric Le Berrigaud from Bryan Garnier. Please go ahead.
Eric Le Berrigaud
Yes. Good afternoon.
Three questions please. The first one relates to margins in pharma and Sandoz.
And the way sales to other segments and another revenues I’ll contributing to the margin increase in the quarter. Could you maybe at least for Innovative Medicine way contributed more than 100 basis points out of the 190.
Explain what is behind especially the sharp increase in other revenues and also sales to other segments is there has been any shifts from corporate into the various divisions? Because it looks like there is a double-digit increase where there is a significant decrease in corporate.
And second point on Lutathera. Perhaps, again, three questions.
First, to understand how is it used and very late in line, like second, third line. Mainly second why does no impact on Sandoz statin, I guess, to Sandoz statin.
And then maybe to remind us what your plans are to move it in earlier lines in the future. And third, on Sandoz Europe.
Again, just to understand how the trajectory of the biosimilars could be in year two. Because we can understand that now rituximab, for instance, sent in Europe getting to the second year.
So how does it look like? Are you able to increase volume?
Are you facing significant price decrease? Are you keeping your market share?
Because we see the brand names still going down, but if it looks more flat for the biosimilar then probably there is some explanation beyond it. Thank you.
Vas Narasimhan
First on other revenues Harry?
Harry Kirsch
Yes. So on the other revenues, as you mentioned, mainly driven by Innovative Medicines.
This is basically the profit split and royalties behind – so from that standpoint kind of margin that are central from the profit split where we have margin efforts in the SG&A line and then some true-up and limited royalties on other revenues as well as – royalties from U.S. profit split.
So that’s the main driving the other revenues up main driving the other revenues up because there’s no change in the structure of how we work in corporate and respective divisions. We have seen that – you may have seen this in the corporate line, that vaccines IP- related royalties have come down significantly and therefore increase in the corporate costs line and core corporate expenses.
Vas Narasimhan
Thank you, Harry. And Lutathera, Liz?
Liz Barrett
Yes, sure. Lutathera is indicated for second line in your tumors and that’s what our growth is and As traditionally seen and typically seen in this market, obviously, some of the patients initially have been to even more than two lines.
You’ve seen the layer line, but we do expect to become standard of care in second line. They haven’t seen any impact on Sandostatin because there’s couple of things happen with the dynamics of Lutathera is one, you do have to come of Sandostatin temporarily but that trials were done followed by Sandostatin.
So once the Lutathera treatment is complete the patients go back on to Sandostatin and I think that we believe the Sandostatin will continue to be first line standard of care but we are considering looking in investigating Lutathera in early lines of therapy.
Vas Narasimhan
And lastly Sandoz biosimilar Europe, Richard.
Richard Francis
Yes. Thank you for the question.
So the question sort of how you think – how we should think about the growth rate. So first I’d like to sort of point that obliviously the court we had a 21% growth rate in biosimilars.
Now of that base business which you sort of hold the non-launch business in Europe, also performed very well. And we continue to see good uptake on both rituximab as well as etanercept.
As we move forward, I think there’s a good opportunity to continue to keep growing these products, obviously that the biosimilar penetration hasn’t matched. But at the same time, we do see some back of the originator and that generally is in the form of prices.
That gives some variability. But we still see these growth brands as we move into next year.
So I hope that answers your question.
Unidentified Analyst
Thank you, Richard. Thanks, Eric.
Next question please.
Operator
The next question comes from the line of Michael Leuchten from UBS. Please go ahead.
Michael Leuchten
Thank you. Two questions please.
One on Aimovig. For patients that are coming off the three drop program, I wanted to share any data to show what happens to those – to commercial some of that.
Any color would be helpful is on the early days. And a question on Alcon.
Given the CyPass withdrawal, I was wondering how you measure the potential impact on our Alcon, given that the business has spent a lot of time rebuilding trust to do with the physician community and surgeon community. Is there any way you could quantify touch points?
Any collateral damage for the business if any? Thank you.
Paul Hudson
Thank you, Michael. Paul on Aimovig.
So, firstly, we’re delighted with the uptake of Aimovig in the U.S. and in deed, it reads across very nicely to what we think will happen in Europe reimbursement in Europe, the unprecedented demand bodes well for choices made.
As for – we’re not sharing data yet for the conversion. I think you’ll appreciate clearly that our objective earlier on in the launch was to give physicians and patients opportunity to use the meds unencumbered, find out if responder and just how good of a responder.
And that’s proven out to be exactly as we thought with the significant uptake. It’s also worth mentioning as well because as we get to the end of the year and into next year and start talking about – or our partner will start talking about the U.S.
dollar sales, that we are running both the hub at the high touch with neurologists and the retail approach. So, we feel that we’ll be unique in offering both channels to get to patients.
So, we feel good about how we’re going to convert and when we’re going to convert it, but I’m not going to share that data right now.
Vas Narasimhan
Thank you, Paul. And on CyPass, situation Dave?
David Endicott
Yes, on CyPass, probably the best way to think about the impact of a long-term relationship with the surgeons. I think we feel really good about what we did around how we handled this.
It was done with a lot of scientific advice from folks we know well, but also in conjunction with the agencies. We’ve exposed all the data at the STRS.
We’ll show it again at AAO. We made it available to people on our website.
Obviously, we continue to work with the agencies around the world to do the next thing we can to see what we can do around the product for long term. The important part of this, the Surgical business grew 7% in the quarter.
It also continues to benefit from a lot of ATI push, I think kind of gives you the best metric on how we’re doing with the surgeons. I think surgeons appreciated our proactive assertive response to the signals we saw.
Michael Leuchten
Thank you, David.
Vas Narasimhan
Thank you, Michael. Next question please.
Operator
Your next question comes from the line of Kerry Holford from BNP Paribas. Please go ahead.
Kerry Holford
Thank you. Just two questions left for me.
Kymriah, just interested to get your view on the sales ramp so far that delivered – internal expectation? Are you comfortable with the current consensus forecasts for $200 million next year and also just to understand why you’ve taken on board the third-party manufacturing this asset in China is selling that biomedicine’s group?
Is that to supply the local market? And then on Gilenya just following the positive IP ruling last July, can you remind us of the next steps here in terms of timeline?
Thank you.
Samir Shah
Thanks, Kerry. On Kymriah, Liz?
Elizabeth Barrett
Samir, sure. Thanks for the questions.
On Kymriah, where we are today, we’re actually above our expectations given the manufacturing challenges that we’ve had, I think that actually responds to physicians really being excited about the opportunity to bring Kymriah to their patient. So, it’s hard to tell where we will be if we didn’t have the challenges, but I think what we’ve seen is that centers have continued to order Kymriah despite this because they really think it’s important for their patients to get Kymriah.
So, we’ve been, the good news is we’ve actually been able to deliver the therapy to most of the patients that were really pleased to be able to bring this therapy, the patients on China, as you say is because we do need to have manufacturing in China based on China law and we also expect that they’ll be able to assist us in gaining access to patient population in China. So, I think what you’ve seen over the last few months is we’ve expanded our footprint for cell therapy manufacturing around the world.
I think that shows that we’re committed to providing access to this important medicine around the world.
Vas Narasimhan
I’ll just add on Kymriah. When you look longer-term, you really see a long-term play, and we are quite confident in the profile of the medicine, which is why we invested in resolving the manufacturing issue in the U.S.
We announced the deal with Cell for Cure in France. We announced we’ll be building a facility here in Switzerland.
We announced the China facility to really give us the global supply chain that we need. And the reason we do that, as Liz points out, is Kymriah has a really unique profile we’re learning.
It’s a profile that hits the sweet spot between strong advocacy and solid safety can be used in the outpatient setting. And when you think longer term about this evolution of this space, it’s really going to be about moving to earlier lines of therapy, where the T cells are less exhausted and you can generate stronger responses.
And you want to be a safe profile medicine in order to be able to do that. So our aspiration with this is to get across T-cell lineage cancers, get into earlier lines, have global manufacturing scale and be able then to really make this into a significant medicine for Novartis.
Now with respect to the Gilenya IPR, there’s no new update from what we have told I think in the last quarter. We have filed the lawsuits against the relevant parties.
We’re waiting now the next steps with respect to the various court cases and what these various parties might do. As soon as we have any further update, of course, we’ll keep you all aware.
Thank you, Kerry. Next question please.
Operator
Your next question comes from the line of Seamus Fernandez from Guggenheim Securities. Please go ahead.
Seamus Fernandez
Well, thanks very much for the question. So, just a couple here, I don’t know if anybody has any questions on Aimovig yet.
But it’s just interested to know a little bit of how we should be thinking about the evolution of gross-to-net and pricing in this area. Obviously, we’re seeing some spectacular uptake of the product.
But there is a speculation and awareness from a lot of free drug is obviously, entering the market, because payers have not really supported yet. So, just wondering how Aimovig is going to evolve in terms of gross-to-net pricing in the U.S.
and how you feel. Once that occurs, how the market is likely to shift in terms of the uptake.
And then the second question is actually on QAW. I noticed in the first two trials that Novartis has reading out for QAW are on FEV1.
The benefits that we’ve seen on FEV1 so far have been somewhat limited with the antibodies, just trying to understand how your team has actually managed to – or is managing those trials for success given what we’ve seen on the FEV1 endpoint in the high eosinophil type area. So, thanks so much for the questions.
Vas Narasimhan
Thank you, Seamus. So, on Aimovig, Paul.
Paul Hudson
Yes. I think – I’m not going to comment on the gross-to-net, and in fact, just to be clear – Amgen take the lead on that decision ultimately in the U.S.
I don’t think we should get confused about free drug and trialing with what that means ultimately for gross-to-net. We were launching several months ahead of competition that [indiscernible].
Again, we wanted to make sure patients get to try it. It wasn’t about coverage or commercial insurance.
It was about trial. And you’ve also seen, as recently as yesterday, an update from Express Scripts about the fact that we are already part of that plan, it wasn’t just recently, it was from the beginning.
So we know overtime, that the volume has to be converted to commercial patients. And we feel again, very confident in how to do that, and we have the plans in place to do it.
So, I probably wouldn’t have much to add, I think that’s the problem there.
Seamus Fernandez
[Indiscernible] on QAW pivotals.
Unidentified Company Representative
Yes. Thanks for the question, Steven.
Regarding what we saw in Phase II, as you know, our QAWs are the only DP2 antagonist to show improvement at FEV1, asthma control and reduction in sputum eosinophils. And we have our ongoing Phase IIIs, which are luster 1 and luster 2.
We expect to see results in the second quarter of next year. And we have that currently powered at greater than 90%, 40% relative risk reduction in the rate of moderate-to-severe asthma exacerbation.
So, we’re looking forward to seeing the results in the exacerbations for next year.
Vas Narasimhan
And just to be clear, where we try to position QAW is really ahead of the monoclonal antibodies. We know we need to show exacerbation reductions that will enable that to happen, but our absolute aspiration is the struggle to demonstrate they can be used for biologics and also be used in children, where we also have a program to ensure that this pediatric dosing available over time, so that we can really cover the space of severe eosinophilic asthma.
So, thank you, Seamus. Next question please.
Operator
The next question comes from the line of Marietta Miemietz from Prime Avenue. Please go ahead.
Marietta Miemietz
Okay. Thank you very much for taking my questions.
Marietta from Prime Avenue. Just a few points of clarifications really.
One is following up on question on Kerry’s Kymriah. How should we think about long term about payer rates to third parties?
In terms of China, should we think of your partner as more of a glorified PMO or someone gets meaningful royalties or something potentially even approach a profit split? As we look into the really long-term and think about Kymriah potentially being a mega blockbuster, what sort of royalty rate should we assume for the various regions?
Also, a couple of questions on the Endocyte deal. The first, in terms of the positioning.
I understand it’s going to be much broader than the where your pharmaceuticals currently going into prostate cancer. But ultimately, in the bone mets phase, is my understanding correct that you would still be competing because you wouldn’t be giving two radio pharmaceuticals, one treating just the bone met and one treat effectively, the bone met plus something else?
And then the second question on that is also, I mean given the somewhat checkered history of radiopharmaceuticals in prostate cancer, would you say that you don’t expect any similar problems for your product because it’s much more of Endocyte product because it’s much more targeted? Or are there any particular learnings for your own clinical programs, in particular, any tumor settings or patient segments that you want to go after?
And then just a small point of clarification on AVXS-101. Vas that your earlier comments that gene therapy is likely to be foundational.
Are you saying that you expect orals to show lesser efficacy in the vast majority of patients and therefore the gene therapies should remain or should become standard of care for the foreseeable future? Or was that comment really just related to the pent-up demand and bowl of the patients and you effectively saying that you think that if you look at the cumulative commercial opportunity longer term, most of that will have gone to the gene therapies before the orals actually hit the market?
Vas Narasimhan
So first on Kymriah global, Liz?
Liz Barrett
Yes, sure. I mean I think the way that you should look at it, that we are committed, as Vas explained, is to bringing this important therapy around the world.
I don’t think there’s any additional royalty or other things that we have to think about beyond what we already know. On the CVNG [ph] and partnership in China, I think we look at us very much as a partnership.
They will be manufacturing for us, and they will also work with us to gain access there, but we’re not expecting any type of profit share there. So I think that pretty much answers that question.
It’s really important, again as Vas said before, to understand that we’re in the long game with cell therapy and particularly with Kymriah. And we’ve seen and we feel like our key stakeholders and physicians and patients are excited about Kymriah, and we actually continuously get requests from around the world to have access to this to this medicine.
So it’s important that we do it and do it in the right way. And we’re planning to do that.
Moving to the prostate and to Endocyte, I think there’s again a little bit of a misunderstanding. This therapy is for all patients to treat prostate cancer.
I think that’s the most – the clearest way that I can explain it. It’s not to treat a side effect or any other part of prostate cancer is to treat prostate cancer.
And what’s happening in prostate cancer, I think it’s really important to think about the evolution of what’s happened in prostate cancer, with antiandrogen therapy, particularly the novel antiandrogen therapies, are moving into the non-metastatic settings. So you’re seeing the need for more therapies in the metastatic setting.
So you’re seeing the need for more therapies in the metastatic setting. And so we see that this will be an important medicine for all prostate patients with PSMA, that I noted before, it’s about 70.% to 80% of the patient population.
I think we demonstrated with – through the launch of Lutathera, that we can bring this important therapy to patients, and that physicians and centers and nuclear medicine physicians are interested in and excited about bringing these types of therapies to patients. So I think we felt very good about the prospects for the prostate cancer area.
It’s a large market, and these patients are in need of additional therapy.
Unidentified Analyst
Can I just – sorry can I just clarify on that point because I thought that the vast majority of metastatic patients the first metastases that develop and the main metastases are at the bone met. So are you basically expecting to be as good on bone met as other therapies, but have the broader application?
Or [indiscernible] separately.
Vas Narasimhan
Let me try one more time, Maria. When you think about radiopharmaceuticals traditionally conceived, you’re infusing a radioactive compound systemically IV.
And those radioactive compounds have certain affinities. So radium has affinity in places where there is calcium.
So radium builds up in the bone. So you have systemic side effects.
And if you don’t have a very targeted approach to all of where you find the relevant cancer because this is really infusing a radioactive agent. Radioligand therapy, which is what we do with Advanced Accelerator Applications and what we do here with Endocyte, links a scientifically well-understood ligand that’s specific to a specific cancer that links to a radioactive particle through conjugation chemistry.
In the case of prostate cancer, there is a well-understood androgen called prostate-specific membrane antigen, PSMA, which is used as a diagnostic and ultimately used for treating the cancer. So what our aspiration is, based on all the science we understand, is that the these PSMAs are overexpressed on prostate cancer cell.
So wherever you find prostate cancer in the body, you will be able to treat with radioligand therapy as that by Endocyte. Our expectation is we will be able to work well in bone met, but more importantly, we will work well for anywhere in the body that you find prostate cancer.
And then we hope to create overall survival benefit and progression-free survival benefits in the indication of prostate cancer. And then on AVSX-101 as a foundational therapy, really, what I – what we believe, and we have to ultimately generate data to show there’s an SMA 2, 3.
But on SMA 1, we’ve clearly shown this is the foundational therapy, potentially lifelong, clear and compelling efficacy, remarkable efficacy. And so far, what we’ve seen over the patients beyond four-year consistent effect.
Now in SMA 2, 3, we have the studies running mechanistically, we believe correcting the SMN1 gene fundamentally is want you want to do here. And that’s what we’re trying to do with this and that should enable the speed of action and the hopeful clinical benefit that you want to see in SME type 2, 3.
Now we need to show that. We believe gene therapy would be foundational in those patients as well.
I mean, we always have to remind ourselves here that this is an absolutely terrible disease. You need patients who have these disease, if you meet their patients, this is an absolutely devastating condition.
So having benefits that are quick, saving what motor neuron are available still in the body, enabling function has a huge, huge impact. So when we look at this from a distance, we start to say, well, these things look all very similar.
Actually, these differences matter massively to the patients involved. So I think that’s what we believe will ultimately here today with respect to onetime gene therapy for these patients.
So last question.
Operator
The question comes from the line of [indiscernible] from Goldman Sachs. Please go ahead.
Unidentified Analyst
Thank you. I have two questions please.
The first one for Paul. How do you categorize the recent pricing comments from J&J on kind of the information market?
And secondly, just more broadly on the pricing team. Can you talk a bit about what are you seeing as it relates to kind of the IL17 market and kind that on the migraine side, where we saw headlines from Express yesterday choosing to leave a certain products off that – describe for us what you’re seeing in that market.
And then secondly, as I look at your early-stage clinical trials, it seems like you got a bunch of assets forward looking at NASH. How would you categorize your interest in that space?
And then conversely, what’s quite unique is not a lot of I/O assets on your early-stage clinical trial, is that now a deprioritized area from your perspective? Or are they just kind of just further along?
Vas Narasimhan
So with respect to pricing in IL-17 and CGRP, Paul, any comments you want to make?
Paul Hudson
I’m not aware of any comments that have been made externally. I think just a couple of observations.
We work very hard to affordability to make sure that those need the meds can get the meds. And I think that’s what our real priority is.
And we have shown to be skillful in our work with payers and PBMs alike. So perhaps, more to add to that.
Vas Narasimha
On NASH, we have a lead compound called LJN452 [indiscernible] which is FXR agonist synthetic, which we believe has the best-in-class profile. We’ve completed two steps of the Phase IIb studies for now and the final dose escalation.
We believe because of the profile, of the product, we can avoid pruritus. We can avoid LDL elevations and get the dose effective dose much higher than other established therapies.
Given that we have that product, we’ve announced collaborations with a few external parties on combinations as well as our own deal with for amikacin from Conatus where you have a combination trial ongoing as well with their compounds. We also have an alliance with Allergan to do a combination trial here.
Our belief is an having that linchpin molecule and having the FXR will enable us to overlook combined with multiple other agents. We play a long game here.
We know there are many other companies in Phase III. We think understanding the underlying biology and then having the real best-in-class agent is the way forward.
And NASH, so stay tuned as we get more results. With respect to I/O, I wouldn’t say there’s a change in strategy.
I say is we – observing the external environment have held I/O to very high standards. And we want to ensure that we see either single-agent activity or a situation where we’re confident that the activity we see can be attributed to our I/O compound.
I would note with, canakinumab, we have a pretty large Phase III I/O program that is validated based on studies and analysis of a 10,000-patient study published in the New Land General Medicine we are in adjuvant lung cancer first line and second line lung cancer. We’re also in CAR-T cell therapies.
We continue our work across a full range of I/O assets that we brought in. And by last count, we have either tied or leading number of I/O assets that are in the early-stage clinic.
But from my perspective, we want to hold them to a higher bar. We want to really ensure we see single-agent activity.
And then in combination, really be sure that the additional agent is giving a benefit so we’re that really creating value for patients and for the healthcare system.
Vas Narasimhan
So I think that’s the last question. I appreciate everyone joining the call, and of course, appreciate your interest.
And all of you investing in our company, we appreciate your support. So thank you again, and have a great day.