Thank you very much and thank you to everybody for participating in today's call. And we appreciate very busy day for you all as lots of companies are reporting out. Before we start, I just want to read you the Safe Harbor statement. The information presented today contains forward looking statements that involve known and unknown risks, uncertainties and other factors. These may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements.
For a description of some of these factors, please refer to the company's Form 20 F and its most recent quarterly results on Form 6 ks that respectively were filed with and furnished to the U. S. Securities and Exchange Commission. And with that, I'll hand across to Vas.
Thank you, Samir, and thanks everyone from my side as well for joining today's conference call. With me today are Harry Kurz, our Chief Financial Officer Mary Franczchudin, our President of Ardis Pharmaceuticals Susannah Schaffert, our President of Ardis Oncology John Tsai, our Head of Global Drug Development Richard Stoner, our CEO of Sandoz and Shannon Klinger, our Chief Legal Officer. So if we move to Slide 5, I'd like to start out by providing some perspectives on the Q3. As you saw, we delivered very solid results. I think it's important to put those results in the context of COVID-nineteen and the impact it's had on healthcare systems.
Despite that impact and despite the impact of those health care system disruptions on some of our legacy brands, Because of our key growth drivers, because of our execution on launches, we were able to deliver solid sales performance in line with Q3 of last year, 4% sales growth year to date and strong operating income performance core operating income performance was 11% in the quarter and 16% year to date. As important was our ability to continue to deliver on our innovation agenda. In the quarter, you saw important approvals, KOSIMSA in the U. S. For relapsing forms of multiple sclerosis, multiple approvals for COSMIC, PICRAY and in some indication expansions as well for Xolair.
We had multiple positive readouts in BeoVu in DME, ADL-one in CML and importantly a range of readouts as well for LNP-thirty three atacopan. Our Factor B inhibitor, which we believe to be the next one of the next major medicines for Novartis. And we also received positive CHMT opinion for Alexion hyperlipidemia and dactyl for sickle cell disease. So a solid strong quarter really for delivering on innovation. There were also multiple important designations we received, both for LNP-twenty three and also for LMI-seventy, orphan drug designation for Huntington's disease.
And I'll say more about that in a couple of slides. Moving to Slide 6. Turning to our growth drivers. There were strong performance across our key growth drivers. Some of the highlights include Entresto growing 45% Bulgensma having a strong quarter with strong uptake in Europe growing 79% Cosentyx growing 7% ahead of a challenging market right now in dermatology, but still demonstrating its overall strength in both dermatology and rheumatology and exceeding $1,000,000,000 for the first time.
And solid performance across the full range of our oncology portfolio. You also see Mayzent beginning to accelerate and continue solid performance for launches such as PickRay as well as Lutathera. Now when you look overall at our key growth drivers, they're now accounted for 50% of our sales in the quarter in Q3. And I think that shows the transition from our legacy portfolio to our next wave of innovative medicines as well, well entrenched and continuing at pace. Moving to Slide 7.
I just wanted to say a word specifically on ZOLGENSMA. ZOLGENSMA's cumulative sales since launch now has exceeded $1,000,000,000 You can see on the left hand side of the chart, we achieved sales of $666,000,000 year to date with strong growth in Europe and also recovery in the U. S. Just to say a few more detailed words about the geographic highlights. In the U.
S, we saw a rebounding from the pandemic disruptions we saw throughout the summer as well as in the spring. And that, I think, is allowing us to get patients tested again and on treatment. 74% of newborns are now being screened for SMA, and we see that rate continue to grow. And of course, in states with newborn screening, Zolgensma tends to have very high shares. We're also seeing an overall shift to the incident population away from switches from nusinersen.
You can see 83% of our sales in Q3 were switches, where new starts from an incident population versus 34% in Q3. In Europe, we're seeing very solid uptake. 9 EU U. S U. S.
Marketplace is as a country comes on board, we see a bolus of patients come on to Zolgensma, then we move back to the steady state and then we get new countries on board. So in line with that, Germany delivered 50% of our ex U. S. Sales in quarter 3. We continue to see very strong uptake in Germany.
And now we'll expect to see multiple other countries start to come online in the coming quarters. The majority of the early patients are coming from prior treatment with Nucynus. And then over 30% of patients thus far have been over 2 years of age, given our broader label in the EU. Now looking ahead in Japan, we see rapid uptake with the immediate following full reimbursement. We've had an approval recently in Brazil, and we're expecting multiple approvals around the world.
So we continue to believe ex U. S. Will be a key driver. The U. S.
Should stabilize now post the COVID situation, and we expect to reach a steady state on our U. S. Sales, and we continue to expect Zolgensma to be a strong growth driver for Novartis. Now moving to Slide 8. Sandoz year to date sales were in line with prior year, and there were really two sides of the Sandoz story.
When you look at the biopharmaceutical sales on the right hand side of this chart, you see that we grew 13% in Q3. And in the 9 months year to date, we've grown 20% with biopharma, but primarily our biosimilars business. But you do see the drag of our retail sales was minus 6% in the quarter and minus 4% year to date. That's been primarily driven by an oral solid decline in the U. S.
As COVID-nineteen has impacted patient traffic and also some similar dynamics we see in Europe as well as after the Southern Hemisphere flu season. Now importantly, we've been able to maintain our profit trajectory with gross margin, increase in both products and productivity, reduced SG and A expense. So overall, we have made some small adjustments to our Sandoz top line guidance. So overall, it feels good about our margin progression in Sandoz over the course of the year. So moving to Slide 9.
I want to take a step back again and provide some perspective on the overall trajectory of the company and give you some details on some of our pipeline facets. When you look at the outlook for the coming years, we continue to have strong end market growth drivers. We're in the midst of a range of major launches, multiple novel assets in our mid stage pipeline, and I've been pleased to see multiple analyst reports now appreciating the depth and breadth of our mid stage portfolio, which we believe is one of the best, if not the best in the industry, with 80 submissions planned, 50 plus late stage programs. And increasingly coming into focus as well will be our life cycle management program across many of our in market growth drivers, as you can see on the right hand side of this chart. Now turning to Slide 10, I wanted to provide some more detail.
And I'll go through the slide in a little bit of a slower pace, Slide 10 and 11, just to make sure you have full clarity on where we are in the various pipeline elements. It's important to note that we are seeing on select instances delays due to COVID, and those COVID delays typically are in the range of 3 to 5 months. We're transparently reflecting that in our documentation to all of you, so you can see where we are. But overall, I think relatively speaking, our portfolio has remained resilient and largely on track despite the massive disruption of COVID all around the world. Now with Lekvio, you've seen our EU positive CHF opinion in the U.
S. We've completed the most parts elements of the review with the FDA, including the full clinical review. The only outstanding item now is a single manufacturing inspection, which we're working with the agency on and a facility in Italy. We've provided extensive documentation and currently work with the agency to try to maintain the action date of December 2020. On ofatumumab, you've seen, of course, the strong U.
S. Approval and Barry Franz will provide you more context. EU approval is planned in the first half of twenty twenty one. Now with respect to Entresto, 2 critical and important life cycle managements in preserved ejection fraction and in the post MI, the FDA has released a notice today that we will have an ADCOM for the preserved ejection fraction filing in December. We're fully preparing for that advisory committee and look forward to those discussions.
The FDA action is continues to be in the Q1 of next year. Now with respect to AveXis-one hundred and one IT on the partial clinical hold, we continue to work on our proposed confirmatory clinical trial study and we'll plan to engage with FDA. Our hope is that we can come up with a lean program that will enable us to move extremely quickly, but it would be premature to provide any guidance on timelines at this point in time. So we don't have any further guidance on specific timelines on AVXS-one hundred and one IT, and we'll continue to provide you updates as we continue those discussions with the FDA. There were a few notes this morning also noting the leglizumab timeline.
We do expect the trial to read out on track, fully enrolled and to read out in the second half of next year. However, given the COVID disruption, we are now forecasting that the submission would be pushed into the 1st part of 2022. Now moving down the line, the next item I wanted to highlight was canakinumab or Canopy 1. As you know, enrollment is complete. The DMC did recommend a continuation after without change after the interim analysis, so we remain fully blinded to that study.
The full readout is expected in the second half of twenty twenty one. And similarly, Canopy II is fully enrolled, and we expect the readout in the first half of twenty twenty one for that program. And lastly, I wanted to note on Kithcali that we did expand our adjuvant NATALY study by 1,000 patients, learning from the recent readouts from some of our competitors to ensure we maximize the success of this medicine in the adjuvant setting across both intermediate and high risk patients. As you know, there's a unique profile here with Kibstaly, the most potent CDK4 inhibitor, which we believe is most important in this setting and also 3 years of treatment in this patient population with a 400 milligram dose lower than what we have in the metastatic setting to really ensure patients can stay on therapy. We're optimistic about this program and look forward to continuing to provide you updates as it progresses.
Now moving to Slide 11. On the emerging pipeline assets, many of these we'll provide more details on our upcoming meet the management. I mentioned at Tacopan, I'll go through some more details in the next two slides, but a range of positive feedback, including positive Phase 2 results PNH and C3 gs. We're on track now to have a single PNH pivotal trial for the frontline and combination study to start in 2020 as well as pivotal studies in both C3 glomerular nephropathy and IgA nephropathy to start in the first half of next year. Moving down the line, the other asset I wanted to spend a little bit of time on is vareniplam, our mrRNA splice inhibitor, which we announced to receive orphan drug designation for Huntington's disease.
This was based on extensive preclinical data, which we expect to be published in the coming months as well as clinical data from our SMA trial in which we were able to look at Huntington RNA expression. We believe BranaPlan's RNA splicing mechanism has a unique profile to be able to tackle Huntington's disease as a potentially once weekly, we'll have to see the final dosing, oral therapy, and we'll plan to start that Huntington's Phase IIb in the 1st part of 2021. Now in terms of oncology, probably the one asset I wanted to spend a moment to highlight was our SHIP-two inhibitor that is in a broad range of combination studies, multiple combination studies with spartolizumab, Kisqali, mazaritinib as well as Mirati's G12C. And we're working very hard to finalize some of those early results, which we hope can inform pivotal studies in the combination path going forward across a range of solid tumors. So moving to Slide 12, just briefly on emtacopan and PNH, this was data we recently presented.
It demonstrates that we were able to significantly reduce residual hemolysis in eclizumab treated patients and return their hemoglobin to normal. It's important to note there is a significant proportion of eculizumab treated patients that don't reach goal. And we believe as an add on therapy, this is important medicine. But even more importantly, you can see in the black squares, patients that were able to move off of their eclizumab treatment and maintain their overall hemoglobin levels, which is the basis of us going forward as a monotherapy as well in this indication. Moving to the next slide.
Similarly, in C3 gs, we see a very strong result. This data was presented over the weekend just recently. It demonstrates a significant reduction in proteinuria. You can see a very impressive P value as well as importantly a stabilization of renal function through as measured by EGFR, again a very clean, safe, tolerable profile. This medicine with this data was able to receive EU prime designation, I think the EU's highest designation with respect to these sorts of medicines.
So very exciting data for LNP-twenty three. Now lastly, moving to Slide 14. Over the course of the quarter, you saw us making important strides in ESG across all our operations. It is our absolute goal to be a leader in ESG across large companies and in the health care industry. We adopted ambitious targets in terms of access to innovation, our global health programs committing to full carbon neutrality that's on top of already committing to full neutrality in our own operations by 2025.
We track, we measure, we transparently publish our target annually, which I really think is unique amongst the companies in our sector. We launched the 1st sustainability linked bond and linked to social targets, particularly access to medicine. The bond was oversubscribed. And we also received upgrades to ESG scores from a range of third party rating want to be, but we continue to make important progress on this front. Okay.
And then just a follow-up on the want to be, but we continue to make important progress on this front. So with that, I'll hand it over to our Chief Financial Officer, Harry Kirsch.
Hey, thank you, Walt. Good morning and good afternoon, everybody. So I'm now going to walk you through some of the financials for the Q3 9 months as well as provide you with an update on our full year guidance. As always, my comments refer to the results of continuing operations and growth rates in constant currencies unless otherwise noted. So Slide 16 shows the summary of our performance for quarter 3 and the past 9 months.
First, I would like to focus on the year to date results on the right hand side. The 9 month performance was strong with sales growing 4%, driving core operating income and core EPS growth of 16%. As you know, sales were mainly driven by Entresto, Zolgensma and Crocentix 7 to 9 months as well as the rest of our growth portfolio. And the core operating income growth at this significant level was driven by the higher sales, improved gross margin from various productivity and cost saving initiatives. Of course, COVID related lower marketing and sales spending also contributed to core operating income growth.
Free cash flow was 8,300,000,000 dollars but down 12% in U. S. Dollars, mainly driven by legal settlement cash outs and lower divestment proceeds compared to the prior year. With respect to quarter 3, net sales were in line with prior year due to the increased generic competition, particularly of Afinitor and XJADE as well as the impact of COVID-nineteen mainly on our ophthalmology portfolio, which we will discuss in more detail later. Despite this, we were able to deliver another quarter of double digit increase in our core operating income, which grew 11%, driven by lower spending and improved gross margin.
Overall, a strong year to date performance, especially given the challenging business environment that we are all in. Now next, let's focus on our core margins on Slide 17, broken down both again by quarter year to date. For the year to date, on the right side, continuing operations core margin was 33.2%, growing 360 basis points with strong improvements in both divisions. Innovative Medicine's margin moved up to 36.3%, up 270 basis points and CONSIDER's margin grew 4 20 basis points to 25.4%. Innovative Medicine's margin was likely to be around 35% for the full year, reaching our mid-30s margin target a couple of years earlier than planned.
Of course, we had a contribution from COVID related to reduced spending, but a significant part of these margin gains were also a result of productivity and cost saving initiatives that we have implemented. The quarter reflects a similar pattern with continuing operations margin at 33.2%, growing 320 basis points and Innovative Medicines margins at 35.8%. Clearly, we are also well on track to deliver on our Innovative Medicines margin target of the mid- to high-30s margin in the midterm. Let's now turn to Slide 18. We have updated the chart that we showed last quarter on the impact of COVID on our different categories.
As a reminder, the graph shows you Innovative Medicine's weekly sales evolution based on a rolling 4 week average index to quarter 4 of last year. We have used the same classification categories as before to allow you to compare. Our recent launches and the detail of what we count in the recent launches, you can see at the bottom of the slide, the footnotes continue to grow quite strongly. The crow drivers line appears to be flat during the quarter. However, all crow drivers performed well.
The flatness of the curve from Gerardo Sample is also a reflection of some seasonality. Now turning to Cosentyx, the dermatology and Cosentyxent rheumatology markets continue to see lower inpatient starts as a result of COVID-nineteen. Prosthetics also was impacted by this trend with growth rates declining during July August. However, there are clear signs of recovery in September. For ophthalmology, in order to understand the market dynamics, it is important to split the market for the back of the eye and the front of the eye.
Back of the eye clinic visits recovered once quicker due to the urgency of treatment. Our key ophthalmology products called back of the eye dominated by Ozentiv and shown in the gray line began to see signs of recovery towards the end of that quarter. The recovery has not been seen in other optimality due to roughly a meaningful impact from COVID-nineteen disruptions and we expect the generics impact on the U. S. Primarily for Dramatone and Ciprovex.
Similarly, our Sandoz retail business continues to be impacted by COVID, as Lars mentioned, as well as the side of the U. S. Orange solids, which we have decided to retain earlier this year. Overall, COVID-nineteen continued to negatively impact demand in quarter 3, particularly in dermatology and ophthalmology. However, we are pleased to see that our recent launches in silk leathers continue to do well.
Now turning to our full year guidance on Slide 19. We continue to expect continued operation sales to grow mid single digits. We are now upgrading core operating income guidance to grow low double digit to mid teens. Within the divisions, we expect Innovative Medicine sales to grow mid single digit and we have lowered December's top line guidance to be broadly in line with prior year. This is due to the decline of U.
S. Oil solids, which we have decided to retain, as mentioned earlier, this year, and the impact of COVID on our retail business. The key assumption for this guidance is that we see a continuation of the return to normal prescribing dynamics in the Q4. September early October patient visit data in the U. S.
Point in that direction. Now I want to go into some of the reasoning behind our guidance and the various pushes and pulls. On Slide 20, we show the actual and expected quarterly development and expectations for the full year. During the Q4, we anticipate for sales, which you see here the left side, lowtomidsingledigits growth. And then for core operating income, let's go to the right side, mid to high single digit growth.
The core operating income growth is expected to be somewhat lower than year to date as we will see some higher investments, including those for the COSYNTRA and LECLIO launch and pre launch investments. Still, after delivering mid teens for core operating income. Of course, if there would be resurgence of the COVID-nineteen impact on the health care systems and prescribing behavior in our major markets, there is a scenario of lower sales growth in quarter 4 versus what we assume here, which could also then reduce our full year sales growth to the 3% to 4% range as we have delivered 4% sales growth in the 1st 9 months. On core operating income, we would expect this quarter 4 at full year level even with potentially COVID related lower sales growth in quarter 4. As we are kind of naturally hedged on the bottom line, should lockdowns happen again due to the expected lower spend levels in such a scenario.
Finally, on Slide 21, as currencies are constantly changing, I want to bring to your attention the estimated currency effects of our results using the current exchange rates. So if late October rates prevail for the remainder of 2020, the full year impact of currencies on sales would be a negative 1% point and our core operating income would be negative 4% point. If the same rates prevail for 2021, the full year effect currencies on sales for 2021 would be a positive 1% to 2% points and our core operating income between 0% to plus 1% point. And as a reminder, we do update these effects in our website on a monthly basis. And with that, I hand over to Marie France for an update on the pharma business.
Thank you, Harry. Good morning, good afternoon to all of you. So let's turn to the overall performance for Pharmaceuticals. The 1st 9 months saw sales growth 6% with continued momentum from our 2 key growth drivers. Q3 saw sales growth of 2% despite the continued COVID-nineteen impact.
Our focus continues to be on driving Cosentyx and Entresto, also leveraging the launch of new indications and geographical expansion, and of course executing on the launches of Beovu, Kysinta and Lexvio. If we turn to slide 23 24. For Cosentyx, Q3 brought us our 1st $1,000,000,000 quarter and 7% year over year growth. Despite COVID-nineteen impact, intensifying competition, biosimilars and pricing pressure. This is a great testament to the complete profile of Cosentyx.
The market growth has slowed versus previous year due to COVID-nineteen. And today, we still see only an estimated 70% to 90% of patients returning versus the pre COVID levels. We continue to see delays in diagnosis and slower new starts across the U. S. And the EU, particularly in dermatology.
Despite increasing competition, Cosentyx maintains a strong position in Durham and is outperforming the market in room. If we look at the U. S, we saw double digit TRx growth year over year, strong momentum in the second half of this quarter. Our focus is on maintaining value in derm, while driving the growth in room.
If we look a little
bit more closely at dermatology, we maintained our market share and our IL-seventeen leadership. And in rheumatology, we're growing 3 times the market year over year and leading in NBRx share around 30%. If we turn to EU, Cosentyx has stabilized market share in derm and maintains rheumatology despite the increasing mandatory use of biosimilars in our key markets. There is significant opportunity for short and long term growth through increasing biologic penetration, something this year has suffered given COVID and expanding our geographic footprint as well as our future indications. We aspire to maintain a strong position in the dermatology space and we're set to accelerate in rheumatology.
In Q4, we expect to return to double digit growth and we see a continued strong growth trajectory for Cosentyx in 2021 and beyond with a potential of $5,000,000,000 and beyond for the brand. If I turn to Slide 25. And to Entresto, Q3 saw another excellent performance quarter driven by underlying strong demand across geographies. Entresto's great momentum is reinforced by how significant the unmet need is and how Entresto is increasingly used as an essential first choice treatment. The U.
S. Weekly NBRx has returned to above 4,000 by the end of Q3 despite the seasonality of the summer and we continue to see strong TRx growth versus previous year. China continues strong growth as well, increasing penetration and account expansion. I think we can say that Entresto is recognized as standard of care for treatment of HFrEF and delivers on its value proposition of keeping patients out of hospital. This is of course especially important right now.
We're confident in the future growth of Entresto. Please remember that about 3 out of 4 eligible half breadth patients are still not on Entresto. We're seeing expansion in China and Japan and potential new indications in the near future. If I turn to Slide 26, so what's new? If we look at 3 post hoc analyses that have recently demonstrated between the role of fluid in wet AMD and vision outcomes.
These recent analyses are showing that more than 50% of the eyes treated with the current NT VGF therapies have residual retinal fluid after 2 years of treatment. What we also see is that above 30% of patients at year 1 of follow-up are dosed more frequently than every 8 weeks. There is a clear unmet need for medicines that provide greater fluid resolution, which is what VeoView offers. We have a full development program that's continuing and we've recently released the results of KITE, our pivotal DME study, which met its endpoints and confirmed the importance of fluid reduction on vision outcomes. We now have approval in more than 50 countries with an updated label.
Ex U. S, we see steady uptake in Germany and Japan. We've seen U. S. Demand recover and stabilize around 1200 vials per week.
We believe that the rare events can be managed and we continue to educate HCPs about how to reduce risk as clinical practice impacts the effects of this medicine. With Beovu's favorable benefit risk profile, we believe we can achieve blockbuster status with this product. On slide 27, if I turn to Kysinta. Kysinta has the potential to become our 1st choice high efficacy DMT for patients, physicians and payers. We're launching with an agile approach and focusing our efforts on HCP adoption, patient initiation and access.
For us, it's key to have broad HCP engagement and have this translate into adoption. Our field force has reached above 90% of our targets either through face to face or through adaptive digital initiatives and we are now covering over 90% of our field force territories as our field force has returned to the field. We've delivered our 1st access wins in record time and we're on track to obtain broad rapid access. Patients are experiencing seamless process in the patient and treatment initiation. This is seen as simple, easy and fast by both patients and physicians.
We're fully focused on execution. 2020 is about driving demand to benefit as many MS patients as possible, and we believe this will translate into solid sales growth in 2021. If I turn to Lekvio on Slide 28, it's a unique product and it addresses both clinical and non clinical barriers. With Lekvio, we will be providing effective sustained LDL C reduction up to 52% with 2 doses a year. Our worldwide launches are progressing rapidly and underway and we just received CHMP opinion ahead of schedule for the treatment of primary hypercholesterolemia and mixed dyslipidemia.
The EU approval is expected in the January December January timeframe for all 27 member states and the U. K. And the FDA action date, as Vas mentioned, is expected in December 2020. I wanted to spend just a moment and talk a little bit about the unmet need in this space. It is extremely high for patients and healthcare systems.
We see above 135,000,000 ASCVD patients in the key markets, 18,000,000 deaths a year. 80% of patients treated on statins are not at goal, and more than 50% of patients are not adhering to treatment. ASCVD costs the health care systems over $1,000,000,000,000 a year in health care spend. This is not because they're not good treatments, but because the non clinical barriers are high, either access, affordability or adherence, which we know will take time and a different approach to resolve. But this product has a long patent life and we're committed to differentiated approaches to make an impact on ASCVD.
With this unique profile and our innovative commercial model, we think we have a real chance of tackling ASCVD at a completely different scale. So in conclusion, we expect to deliver further growth in Q4 despite the continuing COVID-nineteen impact With our relentless focus on our priorities and with our innovative approaches to deliver customer value, we are setting up ourselves for short and long term success. We're driving growth with Cosentyx and Entresto, leveraging new indications and geographical expansion. We're executing on the launch of Beovu, Qsynta and Lexio, and we're preparing the market for our future blockbuster launches. I want to thank the teams for their hard work in these trying times and hand it over to Suzanne.
Thank you very much, Marie France. And let's turn to Slide 30. The oncology business remains resilient, delivering 4% of growth for the 9 months with sales reaching $10,900,000,000 In the quarter, we have seen a very strong uptake of our recent launches, Kis Khali, Kymriah, PICRAY, ADACLYO and the recently launched TAPRECTA. And also our growth drivers Promacta Revolade, Tafilar Mekinist and Jakavi continued very strong double digit growth. The strong momentum across these brands was offset this quarter by increasing generic erosion of Affinitor, XJ JV in the U.
S. And Sandostatin LAR in Europe as well as continued COVID impact in some areas of the oncology business. Due to the pandemic, our radioligand therapy, Lutathera, continued to experience increased number of cancellations and delays in new patient starts, still achieving sales of 109,000,000 But overall, oncology business remains very resilient, and we are confident about the dynamic into the 4th quarter maintained by the strong performance of in market brands and recent launches. Moving to Slide 31. Kisqali continued its very strong growth trajectory with Q3 sales of 183,000,000 dollars 50% growth from previous year, benefiting from the ongoing impact of positive overall survival data from 2 pivotal Phase III trials.
We have seen very strong uptake in market share gain ex U. S, especially in and markets where both post and premenopausal indications were approved for reimbursement in Germany, Italy, France and Spain. And also in the U. S, where Kisqali continued to grow and gain market share in Q3, and this despite patient screening being suppressed and approximately 20% decline in NBRx of CDK4six. And at the moment, Kisqali is the fastest growing CDK4six in the U.
S. We are also pleased to see that differentiation within the CDK4six class is increasingly recognized. And just to remind you that Kisqali has a unique profile versus other CDK4six inhibitors with preferential inhibition to CDK4 over CDK6 and a high concentration to inhibit the target. We are very proud to share with you that Kisqali has received the highest rating as the only CDK4six on the ESMO magnitude of clinical benefit scale, confirming once again substantial benefit for patients based on significant overall survival benefits. On the development side, we are expecting a readout with overall survival results from our MONALISA II study in H21.
Our NACALI trial, as Vas mentioned, in high end intermediate adjuvant breast cancer is enrolling well. We have extended the enrollment in the trial in order to enrich the data set generated with the increased sample size and allow more robust assessment of the treatment effect. The NATALY trial is on track for final readout in 2020. So overall, we are very pleased with the performance of Kisqali. And with that, I hand back to Vas.
Thank you, Susanna. So just in conclusion, as you can see, we had a very solid quarter with double digit core operating income growth despite the impact of COVID on health care systems. Our growth drivers, our launch brands, the key drivers for our mid to long term growth are well intact and performing well. We raised our full year core operating income guidance as Harry outlined. Our mid and late stage pipeline is advancing.
And I hope all of you will continue to appreciate the depth and breadth of our mid stage pipeline in the coming months years. And lastly, we continue to progress on our journey to become an ESG leader with concrete advances over the quarter. We look forward to taking your questions. So operator, we can open the line.
Thank you. Your first question today comes from the line of Mark Purcell from Morgan Stanley.
Yes. Thank you very much for taking my question, Mark Purcell, Morgan Stanley. Just a couple if you may. In terms of Sandoz, I noted on the Meet the Management event, there's going to be a focus on this business. So perhaps could you sort of talk to us about some of the pipeline opportunities you see here?
And over to Harry in terms of there's a significant opportunity on the global manufacturing footprint within this business. What sort of operating margin targets do you believe you could get? And for the pipeline, I mean things like GANELI and Biocon and tinosumab, which you haven't spent much time talking about yet? And then a second one for Harry on the group margin, 3 60 basis points improvement. Could you help us understand the underlying improvement and the sort of COVID related improvement and how sticky that COVID related part might be going forward?
And the last question is on a eskalumab. So a little bit like LNP, it's I guess a pipeline and a product here. Could you help us understand if there's going to be any more sort of interim analysis from the proof of concept data as that matures in the transplantation setting and sort of frame the opportunity in Sjogren's syndrome. I think it's the 2nd most prevalent autoimmune disease. So how significant could that opportunity be ahead of proof of concept data in the second half this year?
Thank you.
Thank you, Mark. So first Richard on Sandoz Pipeline and Global Manufacturing.
Yes. Thank you, Mark. Let's start with the pipeline. We don't generally disclose specific elements of our pipeline, but we have a very strong pipeline across small molecules, but increasingly biologics and more complex products to bring to market with the goal ideally of being at first entry of market at LOE formation across pretty much all our territories. You raised a point about supply.
Actually, first of all, supply this year has been remarkably strong given the challenges that we've had. And also, we've gone ahead and formed Sandoz TechOps over this year. That means that we have far more control over site utilization, investment and strategy that is helping to bring better COG reduction and a greater degree of alignment between the Retail and Commercial businesses and the supply chain, which, as you know, in generics is a key success factor. So thank you.
And maybe just to add one point. We have signed a range of deals over the recent years to continue to bolster the Sandoz portfolio, including the Aspen Pharmaceuticals business in Japan, which helps us build out our injectables portfolio and pipeline in Japan. Again, in Lee, as you mentioned, in diabetes, the BioCon collaboration. So our aspiration is both through the internal portfolio in biosimilars, but also through a range of partnerships to not only tackle the kind of largest opportunities in biosimilars, but also the mid so called mid tier opportunities in biosimilars and build a broad and deep portfolio. I think, Mark, you also asked around margins.
We have an aspiration to get to the mid to high 20s margins in Sandoz over time. This won't be necessarily overnight, but we believe that we have the potential to be in line with the top tiered peers in the generic sector, and that's absolutely our goal. Harry, on group margins?
Yes. First, also on Sandoz. I think as we are in the mid-20s, clearly the mid- to high-20s we see as achievable. And to Marc, we're correct. Of course, the manufacturing initiatives, transformation initiatives are also in a significant way supporting Sandoz margin.
In addition to, of course, will be the biologics success. Given that structurally biologics and the biologics have a higher margin structure than the other part of the business. So very good potential here for the Sonos business. But of course, overall for the teeth and innovative medicines, also very positive. If you look at the 1st 9 months, 3 60 basis points of improvement.
And I think we can almost put it 3rd, 3rd, 3rd. 1 third driven by the gross margin. Also here, of course, the manufacturing footprint and some mix effects that had a positive impact about a third of that 360 basis points. And the other another third, I would say, were the COVID related lower spend levels and another third productivity and sales 4% sales growth, maybe fixed cost pickup. Now we do expect that some of the COVID delays, I understand, will come back.
And by the way, also in the current situation, we do invest into our products where it's possible. Of course, we don't waste money. And some activities are simply not possible or possible only at the lower level. But we do also believe that most of the productivity that we find in this new situation will also stick for the future. And that's, of course, a key element as we work ourselves through next year in the 3 to 5 year plan.
So we expect that with this, we do increase our core margin on the Innovative Medicines business and the company year by year as we continue on our productivity programs and also figure out how to make most of the COVID related productivity initiatives also stick. So overall, on a very good trajectory there.
Thanks, Harry. And then John on iskalimab?
Yes. As you know, Mark, iskalimab is our anti CD40 that we're advancing multiple indications. Our primary indication that we're pursuing is in renal transplant and we've shared some of the data previously. And we're moving forward with an innovative approach that we call Ibox, which is a risk prediction scoring that combines measurements of kidney function. We look forward to bringing that to the market working with the health authorities in the early 2023 timeframe.
That's for renal transplant. You were referring to the Sjogren syndrome, which is an additional indication that we're exploring. And that is moving forward currently in a Phase 2a study, there is an interim reading out in the Sjogren's syndrome population that will not come out until the first half of twenty twenty two. So those are the general timelines, but we are looking at multiple indications for aeskalumab and we're hoping for potential multiple approaches to treating patients.
Back to you, Bhaskar.
Thank you.
All right. Next question, operator?
Thank you. Your next question comes from the line of Graham Parry from Bank of America.
Hi. Thanks for taking my questions. So firstly, on the margin guidance that Harry was just touching on there. So year to date, you're almost into your mid- to high-30s margin target, which I think you've previously pitched as being by 2022. So can you just help us understand when does margin where does margin growth stop?
And so where is it capped at above that level? Secondly, on Kazynta, are there any actual sales in the quarter? Was it all free drug? And how long do you expect the 2 month free drug program to continue? Is that scheduled for all of Q1 or first half of twenty twenty one, for example?
And then thirdly, on the changes on the NATALY trial, so you've highlighted you've increased to 5,000 patients, but have you changed recruitment criteria there at all to enrich the population for higher risk patients or amended the statistical analysis plan to allow a primary endpoint readout only in high risk patients for example? Or do you think that the differences we're seeing between the Ibrance and Vazenio adjuvant trials are actually products rather than trial population related? Thank you.
Thanks, Graeme. On the mid to longer term margin, Harry?
Yes. Thank you, Graham. Of course, we have to first recognize the 1st 9 months margin in our business is usually a bit above the full year as quarter 4 margins tend to be for seasonality reasons lower. So we are in the 1st 9 months at 36. I indicated for the full year, we see roughly 35 for Innovative Medicines.
So we have some room to go for the mid to high-30s. And then we don't put a cap on it, but first you want to get into that range of mid to high 30s. I think most of our large comparable market cap companies are in these mid to high 30s. But it depends also, of course, on the mix of businesses and the launch cycles. So I don't want to put a cap on it at the moment, but first we want to get to the mid- to high 30s.
And we always, always want to ensure that we have the right investment levels at the same time as we drive productivity and resource allocation.
Thanks, Harry. On Kysympa, Marie France?
Yes. So, our focus in 2020 is really just about driving appropriate demand and initiation of patients. In other words, for us, the broad HCP adoption and ease of access and initiation is key. As you know, we have this free drug program and this will be a significant bridge for a number of patients until we get to paid scripts. So, so far our key metrics is going to be NBRx.
We're not underestimating the extra lift it takes to launch a product during this pandemic. That's why we're really focused on driving demand and initiation. We've already seen some early access wins and we're focusing on broad availability for patients. We've seen that with CVS NETNA. We've had our first Medicare win.
We want to ensure that patients have preferred single step access. We believe that Cosinta has the potential of being the 1st choice DMT for patients, physicians and payers because it's highly efficacious, it's safe and it can be administered at home. So that's what we're doing right now in 2020 is really focusing on demand and initiation of patients.
Thanks, Frank. And John on Natalie?
Yeah. Thanks, Graham. Thanks for the question on Natalie. As you know, we increased the sample size from 4000 to 5000 patients to allow for more robust assessment of the overall treatment effect. What I will say is for competitive reasons, we don't want to disclose too much details, but we do believe in the unique KESCALE profile and the overall trial design remains the same.
So what we can disclose is that the enrollments continuing and going very well. We also are using a 400 milligram dose here. And what we've seen so far is that this has been well tolerated, which is different from the 600 milligram dose in the Avance breast cancer patients. So overall, it's going well and recruitment is going very well. So thanks, Vas.
Back to you.
And maybe just to build on John's plan, I mean, we believe that GIPSA is unique and it's focused, as I mentioned in my early comments on CDK4. We also believe with a robust trial in which we limit patients' discontinuation discontinuations in the study, which we think hampered some of the other studies, we have the opportunity to have the broadest indication in the entire competitive set, which would be, of course, a unique selling proposition for Kisgali around the world. So we're quite excited about taking this forward. Thanks, Graham. Next question, operator.
Thank you. Your next question comes from the line of Andrew Broome from Citi.
Thank you. Three questions for Marie France, please, on inclisiran. Firstly, in terms of the launch and marketing, should I assume that the Entresto field force is going to do the bulk of the heavy lifting? 2nd, when would you expect a J code to be issued? I understand they're issued quarterly now, so I'm assuming either 1st or second quarter.
And then finally, just thinking about the degree of cost advantages you have in terms of pricing to payers versus the PCS kind antibody, could you just compare and contrast the COGS on inclisiran versus a monoclonal?
Thanks, Marie France. If you want to take the first, I can tackle the COGS. So on the field force and the J code, MirCos?
Yes. So I mean, clearly, there are a lot of synergies between the field force that we've built with Entresto and what we would like to do with Inclisiran. I think the approach that we're taking with Inclisiran will require us to also build our capabilities in managing different stakeholders such as government and insurance companies and payers and working with systems. So we will have to build additional capabilities. But overall, I think it's clear that when you look at Entresto, when you look at Inclisiran and when you look into the future of our CVM portfolio that there are a lot of synergies that we can leverage across the board.
When it comes to the J code, yes, you're right, they are giving out J codes quarterly. I think you just remind you that a lot of cardiologists in this space are not necessarily set up for the buy and bill process. The systems of care are and many of these cardiologists are affiliated with systems of care. So we believe that through the systems, we will be able to overcome this initial hurdle. That being said, we will be building the capabilities for buy and build possibilities for cardiologists and beyond.
Thanks, Marie France. And then on our longer term strategy and how it links to the cost of goods. We, of course, have the aspiration to take the product broad into the ASCVD secondary prevention market. We have the ongoing secondary outcome study. And then we also have the aspiration to test the medicine in primary prevention and agreement with the NHS to take that forward and potentially additional supportive studies to get us to a primary prevention, which would open up the patient population quite dramatically.
In order to enable that, we, of course, will then have to over time be able to provide this larger volumes and at competitive cost. We believe that as an RNA based therapy with small molecule a small molecule production profile, we have the opportunity to drive these COGS quite low, not as low perhaps as a traditional small molecule, but in that range. The way we're going to do that is we are over time planning to build up our own internal capabilities to produce this medicine. We're working with collaborative group also in the U. K.
To look at next gen technologies. But the aspiration would be certainly to have the cost be a fraction of the cost of a typical monoclonal antibody that would enable, I think, that large volume possibility. Thanks, Andrew. Next question, operator?
Thank you. Your next question comes from the line of Nora Svetlak from UBS.
Hello. Thank you. Firstly, on TSIMSIA. You've been clear about your plans to drive some demand in the short term, but could you outline for us what you think the ramp towards profitability looks like for this drug? Is it quicker than usual because you've made oblitumumab historically albeit in a different formulation?
Then secondly for John on the Factor B in C3 gs, a view from the regulator on what the appropriate endpoint is for a Phase III trial. Is proteinuria enough? Or will you need eGFR? And then maybe finally on Zolgensma sales outside the U. S.
I think you said, Germany is playing a very substantial part. But could you tell us what other countries are contributing meaningfully to revenue at this point? Is it just Japan? Thank you.
Thank you, Laura. So we'll start with the Kysinta ramp, Maritra?
Yes. So I think we have to think about what KYSIMTA is, right? So KYSIMTA is a high efficacy therapy. It's well tolerated. It can be administered at home.
And for this reason, we firmly believe that our position goes beyond the current B cell market. If you think about the fact that 70% of patients are currently on either subcu or oral DMTs and 63% of patients are remain on low efficacy therapies. When you look at what's happening in the marketplace today, it's very encouraging to see the shift to higher efficacy therapies. We know that there are a number of physicians that are not necessarily, don't necessarily have access to infusion capabilities or patients certainly in this COVID period who are going to be looking for options that don't require them to spend time in an IV infusion center. So we believe that the way we should be positioning KRYSTIMTA is in a first line or a first switch.
And that's why the focus for 2020 is really on the appropriate demand, the initiation of patients. If you look at some of the estimates on what the B cell market could look like over the next 10 years, there are some estimates that point us to 35% to 40% of the market. We certainly want to be participating in that very strongly. So what the focus is now is broad adoption, ease of access initiation. We've learned a lot from our previous launches in this space and we know that it's absolutely crucial for us to have strong access and for patients to be able to initiate this drug very easily.
We've got, as we said, the free drug program and our key metrics over the next couple of months is going to be NBRx.
Thanks, Marie France. And then John on the C3 gs LNP and Phase III endpoints?
Yes. For LNP, Laura, I guess we'll call it itokipan, if you guys know the new name for it. In fact, as we look at C3 gs, as you know that there's no therapeutic agent designed to really target the underlying disease, which is complement dysfunction here. So we're really encouraged. And you saw the results that Bas shared in the presentation slide.
So we're really encouraged by those results. Now as you pointed out in terms of proteinuria reduction, this is not a validated surrogate marker with the FDA. So we're currently working with the FDA on looking at both the urine protein creatinine ratio as well as looking at the estimated glomerular filtration rate, eGFR. And what we did see in the Phase 2 studies was that there was benefit in both. So as we move forward, we're capturing both in our studies and looking for the best path forward with the regulatory authorities.
And then lastly on Zolgensma ex U. S, there's, I would say, maybe 4 groups of countries that are relevant: the U. S, of course Japan, as we continue to launch. In Europe, you have some early adopter countries, so primarily Germany and a few other smaller countries. But then we're now working very hard on expanding access in the UK, France, Spain and Italy.
And then the 4th group will be the emerging market countries, which are substantial markets, countries like Turkey, Saudi Arabia and the Gulf Coast countries, Brazil, Australia, not emerging markets, but Australia and Canada. So as the next 12 months unfold, various markets will come online at different points in time, depending on how fast the body the various access bodies move in providing reimbursement. We do continue to see a reasonable number of patients in self pay situations as well and also compassionate use, of course, through our compassionate use program. I'd say overall, the demand is very robust across these markets, both below 2 years of age, but as I noted also a significant number of patients, proportion of patients above 2 years of age as well. Thank you, Laura.
Next question
Thank you. The next question comes from the line of Carrie Holford from Berenberg.
Thank you. Carey Holford. Three questions, please. Firstly, in multiple sclerosis, looking at Gilenya, how much of the sales decline in Q3 is due to pandemic disruption versus the increased competition you mentioned that at which competitor you're losing share to. I wonder if this is also a reflection of you promoting Mayzent and Kazimtori over Gilenya and pushing that to continue going forward.
And ACZ, can I ask you is there another CANOPY-one study before the final readout? And if so, when that might be? And then on Lutathera, I guess I'd like to understand what the risk is here that the disruption we've seen currently due to the pandemic results in a permanent loss of access or interest to physicians and to new patients. How can you retain that interest and that relationship? Thank you.
Thank you, Carrie. So first on Gilenya, Marie Cross in MS.
Yes. So our Q3 Gilenya decline is as expected, and it's been driven by some inventory decreases which should bounce back. We have seen as you know a significant slowdown in the NBRx especially in the S1P class. And Gilenya due to its pretesting and first dose observation has seen a slowdown in the Envirox market. We've also seen a slower recovery in the S1P market versus the others during this COVID pandemic.
We have had lower demand due to increased competition. There are new oral DMTs. And also we have seen some switches happening with other competitors, higher RDs. And the fact that the full organizational focus is on driving new patient starts for KYSEMTA and NASHEN. So Gilenya continues to be a 3rd most prescribed DMT worldwide.
We know it's a high efficacy oral. It's the only DMT prescribed in pediatric patients 10 years or older. In the U. S, we'll continue to promote it in this population or patients who prefer orals, but our focus has clearly shifted.
Thanks, Marie France. On canakinumab, John?
Yeah. For canakinumab in the first line non small cell lung cancer study, Kerry, what Bob did mention earlier in the presentation is that the DMC did meet earlier this month and recommended that we continue the study without modifications and this was an interim as noted previously. We continue to have high thresholds for the interim analysis for both CANOPY 1 and CANOPY 2. The end analysis step or plan for Canopy 1 is in the second half of next year. And for Canopy 2, the end analysis is planned for the first half of next year.
So those are the overall time lines moving forward.
And we do have, Kerry, additional interim analyses, but we're not in a position right now to predict exactly when those are going to happen based on the statistics. We'll of course keep everyone up to date when we have a better visibility. On Lutathera, Susanna?
Yes. Thank you, Clari for the question. So Lutathera was more or less in line with previous year, reaching 190,000,000 and it is, as you rightly say, impacted by COVID. When you look at the different dynamics for the U. S, we had a slight decline of 4%.
But on the other side, in Europe, where the situation opened up again, we saw growth of 10% versus previous year. We remain very confident in Lutathera given the very strong profile of the product. As you remember, Lutathera has demonstrated overall survival benefit over somatostatin treatment, and we see still very high interest for the product. We saw some postponements and cancellation of new patient starts, but we're still activating our plan to further growth. We are reaching out to the community level where over 65 percent of the patients are treated, and we have very encouraging discussions there.
So overall, we remain very confident, and the current softness is mostly impacted by COVID. And as soon as the situation is released, we expect to have new patients taking up again.
Very good. We have a number of questions on the line. So I'll ask the next set of questions. So please limit yourself to one question with no more than 2 subparts. So we can add the next question operator.
Thank you. Your next question comes from the line of Peter Welford from Jefferies.
Hi, thanks for taking my question. Congrats on Gilenya. Just going back to that, whether you can provide us any visibility now on the timing of potential U. S. Generics after I think all the legal cases have now been finalized.
And so can I just go back to John just for a clarification on canakinumab? I know you said that there were other interim analyses I think you said. But is the second half '21 headline data that you're talking about, is that your best estimate for the final readout of CANOPHY 1? Or is that your assessment of when we could next hear, which actually could be one of the next interim analyses? Thank you.
Yes. I'll take I can take both of these. On Gilenya, we, of course, are very pleased with the response of the district court to uphold our patent. We do understand the filer has filed an appeal. So over the next 12 to 18 months, that appeal will now unfold.
We continue to stand by our patents, including some of the more recent past the patents that have been issued. So we would expect, again, a court case that has substantially happened over the next 12 to 18 months. And in the meantime, we continue to operate as planned and continue to aggressively defend our IP. With respect to canakinumab, the final analysis for the second line study is in the first half of next year and the final analysis for the first line study is in the second half of next year. There is an interim another interim analysis for both studies, both the second line and the first line.
Learning from some of the disruptions that have happened with COVID, we would feel more comfortable not providing specific timings until we have a better sense of when exactly those interims will occur. Is that clear, Peter?
That's great. Thank you.
All right. Perfect. Thank you. Next question, operator.
The next question comes from the line of Keyur Parekh from Goldman Sachs. Sachs.
Hi, good afternoon. Hopefully, you
can hear me okay. Vas, would you mind just setting the tone for the Encresto and HFpEF? Based on your conversations with the regulatory agencies, what should we expect to be the focus of the advisory committee? That's one. And then very quickly, secondly for Harry.
Harry, kind of can you just remind us for your priorities for capital allocation as we get into kind of next year? And especially how are you thinking about kind of stock buybacks versus business development? Thank you.
Yes. Kieran, thank you for the questions. On the advisory committee, we'll see ultimately what the FDA focuses on. I think our expectation is 2 major areas of focus. 1, on the primary endpoint, as you know, the centrally adjudicated result was narrowly missed.
The investigator adjudicated result was, in fact, positive and met statistical significance. A reanalysis by an independent group also indicated a positive result. So parsing those various results, I think, will be one major topic. And then looking at the various subgroup analyses, there was a clear trend for benefit in patients with EF up to a certain cutoff, roughly 57 percent as well as in women and how the FDA might navigate all of the above from a labeling perspective. We expect those to be the major topics.
From a safety perspective, don't expect major management discussions. Harry, on capital allocation?
Yes. Hi, Kiara. Hey, Jorg. So thank you. As you probably imagine, there is no change in our capital allocation strategy.
First priority always has the investments in the organic business. The second priority being an attractive growing annual dividend in Swiss francs, which we again expect to pay out in usually March of next year, should AGM as always a 2. 3rd priority, value creating bolt on M and A and 4, for share buybacks. So it depends very much what opportunities do we find. We all know that these are usually on M and A bolt on quite heavy premiums have to be paid.
And so we are super selective on them. And so let's see if we find them up to 5% of our market cap. And should we not find them, of course, share buybacks, I expect always to be part of our capital allocation, but the 4th priority. Having said that, we always do some share buybacks to avoid any dilution from our employee compensation programs. But we don't announce that the ongoing commitment to not dilute our shareholders.
Thanks, Harry. Thank you, KR. Next question please, operator.
Thank you. The next question comes from the line of Simon Baker from Redburn.
Firstly, a question on Sandoz. I wonder, Richard, could you give us an idea of how important label carve outs of generics are for you in light of the recent ruling that potentially renders them illegal in the Glaxoiteva case earlier this month? And then secondly, I noticed on the slides the mention of Lapsterna in a few of the note notes, but no other commentary. If you could just give us an update on where you stand with LUXTURNA? Thanks so much.
Thank you, Simon. On the Sandoz label cohorts, Richard?
Yes. No, it's really an important and interesting topic. I mean, clearly, we're watching the progression now with Teva, I think, going to appeal on the GSK Corig case. Clearly, the use of skinny labels has been a routine route to market, particularly in the U. S.
It really goes against really the provision that was originally put in place. And clearly, as an industry, it's something we need to explore and consider how we challenge.
On LUXTURNA, Mary Franck?
Yes. So as you know, we have the rights for LUXTURNA ex U. S. And we have certainly made a lot of progress in making sure that we prepare centers from a training perspective to manage the product. I will say that during this COVID period, we did see a complete stop to those surgeries as they were considered non urgent.
What we are seeing is we are seeing pickup happen now. So the hope has to be that we can continue to see these children getting use of LUXTURNA. We've seen an increase in approvals overall. We're working on reimbursement and making sure that centers are basically apt and trained to administer the product. So definitely a slowdown, but hopefully for the rest of the year we'll get as many children treated as possible.
Thanks, Mirafont. Next question, operator?
Thank you. Your next question comes from the line of Flora Chesboudet from Societe Generale.
Good afternoon, everyone. Thank you very much for taking my questions. Two quick ones. First for Marie France on Maison. Could you please elaborate on what is behind the acceleration of the product and if it is sustainable?
My second question on lislelizumab for John. Could you share with us how you believe you will differentiate these products versus your PTK inhibitor, which is in Phase 2? Thank you very much.
Thanks, Laurent. Mayzent, Marie France?
Yes. So I mean, we have seen an acceleration in Mayzent. We're very happy to show 41% quarter over quarter growth. This is a unique set of patients and Mayzent has unique data in this population showing really great results in the SPMS population. We've seen growth despite COVID and this is just a tribute to the fact that physicians are identifying these patients and are bringing these patients to treatment.
We've got breadth in our Rx. Our patient onboarding is happening and it's easier. So we've improved when it comes to that. And also we have a clear positioning. We've also launched in additional markets.
So we've seen that Germany has above 1,000 patients. We've also recently seen the Knight Nod from the U. K. And we're preparing to launch in China and Japan. So I think you can continue to see this growth quarter over quarter and year over year with MACEN.
Thank you. And John on leglizumab?
Yes. Thanks, Laura. Thanks for the question on leglizumab. As you know leglizumab is our anti IgE that forms free complexes and binds up to free IgE. We did have a publication earlier in the year in New England Journal, which compared lebolizumab in CSU where we showed significant benefits at 42% versus 26% in Xolair.
So based on that, we are moving forward obviously and are fully recruited in our trial for ludulizumab. We expect the readout to be in the second half of next year. You asked about differentiation versus remibrutinib BTK inhibitor. Currently, we're still looking at we're awaiting the full results for remibrutinib in CSU. So obviously for remibrutinib, this is an oral versus leglizumab being a subcu formulation.
So as we get more information on remibrutinib, I think we'll be able to clarify what the differentiation is between the two agents. Thank you very much.
Thanks, John. Next question, operator?
Thank you. The next question comes from the line of Richard Vosser from JPMorgan.
Hi, thanks for taking my question. One, please. You talked Vas in the opening remarks about continued improvement in the U. S. Prescriptions.
We've seen in terms of COVID coming back with a vengeance maybe in Europe. So just your thoughts on how new patient starts and your therapies are going in Europe and outside the U. S. To just give a flavor going into Q4? Thanks very much.
Yes. Thanks, Richard. I think it's a very variable situation. What I do believe is that it's variable by country and jurisdiction. What I think is clearly the case, those health care systems have, 1, gotten better at managing COVID severe COVID cases, understanding when to hospitalize, when to bring patients into the ICU and therefore better manage the load.
I think second, there's a broad recognition, broadly also published in the academic literature that there is a substantial impact of this pandemic on non communicable diseases writ large. And there's a, I think, a broadening desire in the public health community not to see that expand. So trying to maintain patients' visit schedules from in oncology in all of the various noncommunicable disease categories, rheumatology, cardiology, pulmonology, dermatology, ophthalmology, etcetera. And then 3rd from just the economic financial sustainability, healthcare systems are quite motivated based on my conversations to also maintain their normal activities to the extent possible. I think for all those reasons, we certainly are seeing an impact of the 2nd next wave in Europe, but there hasn't been thus far as severe as what we saw in April May.
And as Harry noted, we're hopeful that, that will remain the case. Now if we do see significant disruptions, of course, we'll have to adjust accordingly. And actually, I think it's a similar situation in the U. S. So the U.
S. Appears right now to be a bit more resilient in making sure the healthcare systems operate also I think because of the financial strain those systems have been under. Thank you, Richard. Next question, operator.
Thank you. The next question comes from the line of Tim Anderson from Wolfe Research.
Hi. Thank you for taking my question. This is Richard Wagner for Tim Anderson. My question once is regarding LAG-five twenty five, your LAG-three inhibitor. In Q2, it was shown as a 2023 submission.
It's dropped off of the submission slide. Wondering if you had some underwhelming data with this novel in the way it's changed its prioritization? I know it's not a high probability program, but it's relevant to one of your IO competitors, Bristol Myers Squibb, who have a more advanced LAG-three program? Thank you very much.
Thanks, Richard. John, I don't know if you have the latest on LAG-three. I certainly don't. Maybe Yeah. So,
yeah, based on portfolio prioritization, Tim, we made some decisions. And the area that we were looking at was lag and triple negative breast cancer. And we decided not to move forward in that indication, so that's why it's dropped off.
Thanks, John. Next question operator, I believe it's maybe our last question.
Okay. The question comes from the line of Jo Walton from Credit Suisse.
Thank you. 2 quick ones. Do you have any visibility on Sandostatin LAR generics? And I believe it was mentioned that Sandostatin generics in Europe were a factor. Are there more countries?
Is that becoming a more serious issue? And the second one on Cosentyx, please. I know that you say that there's been a drop in visits to derm, but we are seeing in the 1st 3 quarters of this year substantially higher prescription than sales growth. So there's obviously some increased competition here. And I wonder if you could address the competition angle as much as the lack of derm patients in the U.
S? And I believe in Europe, you said there's now mandatory use of biosimilars. I wonder if you could expand on that comment, too.
Thanks, Joe. So first on thymnostatin. Susanna?
Yes. Thank you, Joe. So as you saw, thymnostatin Phase were declining and this was mostly driven by generic erosion in Europe. At date, there is one generic that has received marketing authorization in Europe and has started commercial activities in limited countries, namely Germany, France, U. K.
And a few other small countries. On the U. S. Side, we know that there's one generic application going through regulatory process. But at the moment, we have no further update.
And then on Cosentyx competitive dynamics, Marita?
Yes. So I'll just start off by saying that it's a very competitive class, and it's getting more competitive by the quarter almost. But despite this, Cosentyx continues to deliver very strong growth. And if I could just take you through it. We had 1st of all, we had our 1st $1,000,000,000 quarter, which I think is definitely something to celebrate.
And we have seen a slowdown in the market. So if we look at the expansion of the market this year versus last year, I mean, there's clearly been a slowdown. There's been more competition. We'll get to the biosimilars question in a second. And what we have seen is we've seen a faster recovery in the rheumatology space versus the dermatology space.
If we look a little bit more carefully at the U. S, we're maintaining TRx share and MBRx share in derm. Even though you see the slower recovery and the increased competition of IL-twenty three, in the wound space, we're actually growing 3x TRx versus the market year over year. So what our aspiration are are have entered and where there's mandatory use, so it's exclusively in some of the markets in the EU and namely Germany, Spain and the U. K.
What we've done is we've actually maintained the share in dermatology after the initial entry of biosimilars And the same with the rheumatology space where we've seen the biosimilar