Sanofi SA

PAR:SAN

Earnings Call Transcript 2021-Q3

[Operator]

Ladies and gentlemen, thank you for standing by. Welcome to the Sanofi Third Quarter 2021 Earnings Call. I would now like to turn the call over to Eva Schaefer-Jansen, Head of Sanofi Investor Relations. Please go ahead, Eva.

[Eva Schaefer-Jansen]

Good morning, good afternoon and good evening to everyone. Thank you for joining us to review Sanofi's 2021 third quarter results followed by a Q&A session. As usual, you can find the slides to this earnings call on the Investors page of our website at sanofi.com. Moving to Slide 2. I would like to remind you that information presented in this call contain forward-looking statements that involve known and unknown risks, uncertainties and other factors that may cause actual results to differ materially. I refer you to our Form 20-F document on file with the SEC and also our Document d'Enregistrement Universel for a description of these factors. With that, please advance to Slide 3. Our speakers on the call today are Paul Hudson, Chief Executive Officer; John Reed, Global Head of R&D; the Global business unit heads, Bill Sibold, Thomas Triomphe, Olivier Charmeil and Julie Van Ongevalle; and Jean-Baptiste de Chatillon, Chief Financial Officer. [Operator Instructions] With that, I'd like to turn the call over to Paul.

[Paul Hudson, CEO & Director]

Well, thank you, Eva, and thanks to everyone for joining our call today. We are truly excited about the outstanding results in the third quarter. The strong performance of our businesses exceeded expectations with double-digit growth, both on top line and bottom line, up 10% and 19%, respectively. Just about 2 years into executing on our Play to Win strategy, the strong set of third quarter results marks another proof point of our focus on growth, and puts us on a clear trajectory to deliver on our midterm financial targets. Dupixent was, again, the #1 driver with a 55% increase in sales growth came from the U.S. and increasingly from global markets as the rollout of this uniquely successful medicine continues across additional geographies, younger patient populations and new indications. Over recent months, we've reported on 3 positive Phase III readouts in prurigo nodularis, eosinophilic esophagitis and in atopic dermatitis patients as young as 6 months. It's truly outstanding and speaks volumes about the game-changing quality of this medicine and the hard work done by all the teams. Bill will tell you more about how we're working on accelerating critical milestones in our pursuit of the greater than EUR 10 billion sales ambition to Dupixent. In Vaccines, we delivered record flu sales in the quarter, reaching EUR 2.4 billion, an increase of 17%. One key to success is our differentiated offering, which demonstrates our leadership in flu and our continuous efforts to improve the standard of care. In the quarter, 2/3 of our global flu sales were generated by our differentiated high-dose flu brands, impressively reflecting their value for better protection, which is also recognized by payers and providers. So in conclusion, these results give us confidence in our growth outlook for the remainder of the year, allowing us to, again, raise full year guidance to around 14% on business earnings per share. Moving on to Slide 5. Let me turn to our targeted M&A activities in the quarter. In line with our existing M&A priorities, we announced 2 bolt-on acquisitions, which strengthens Sanofi's growth areas. Both are a perfect fit with our strategic priorities as outlined at our Capital Markets Day in December 2019. Our deals have followed the same objective, adding exciting science and first-in-class technologies to our pipeline. We're looking for growth opportunities in areas where we have existing capabilities and where incremental cost to succeed with commercialization are low, and hence, accretion can be reached quickly. Starting on the left, our collaboration with Translate Bio's always focused on the development of next-generation vaccines and to leverage TBIO's expertise in messenger RNA technology. Then in June of last year, well before any COVID mRNA vaccines were fully validated, we saw the opportunity to gain full access to TBIO's targets, assets and tech transfer. The acquisition provides us with a fully owned platform, an important pillar in building our center of excellence in mRNA. We're now moving full speed ahead with the first positive clinical data in COVID in hand already. We are committed to have the first modified quadrivalent flu mRNA vaccine enter the clinic in 2022 and to deliver a pipeline of at least 5 other clinical candidates by 2025. Thomas and the team will talk more about this at our upcoming Vaccines Day on December 1. Last month, we also announced our intention to acquire Kadmon. This will bring a recently FDA approved and launched transplant medicine to Sanofi. It is first-in-class science, which addresses a high unmet medical need. Our global scale and existing expertise in transplant will allow us to fully unlock the potential of this attractive asset. Olivier will provide additional details about this significant growth opportunity in just a moment. We were absolutely delighted to find Rezurock fitting into our transplant portfolio, and we remain focused on delivering on our commitments, considering capital allocation priorities as outlined at Capital Markets Day in 2019. I now hand over to John, our Global Head of R&D, to give us a quick update on our pipeline. John?

[John C. Reed]

Thanks, Paul. As indicated on the left side of Slide #6, we continue to deliver strong progress on pipeline execution despite the ongoing pandemic environment and made advances with a number of important late-stage clinical studies. 5 positive pivotal readouts were reported for our pipeline over the last 3 months, including 4 additional indications for Dupixent, 3 in dermatology and now showing clear benefits in the gastroenterology disease. Our anti-PD-1 medicine, Libtayo, also delivered a competitive Phase III performance in frontline nonspell cell lung cancer in combination with chemotherapy. A small Phase III study of our reversible covalent BTK inhibitor known as rilzabrutinib failed to meet the target endpoint in pemphigus vulgaris likely due to, in part, to effects of background medications in the placebo arm, but we will share encouraging Phase II data for the ITP indication at a major medical congress later this year. And we also expect a publication sharing the details of our ITP data in the near future. With regards to recent approvals, we're proud to have launched Nexviazyme in the U.S. and Japan, establishing a new standard of care for patients living with Pompe disease. On the right side of Slide #6, I draw your attention to some of our upcoming milestones over the next 6 to 9 months, including submissions to bring benefits to infants, namely Dupixent in infant atopic dermatitis and nirsevimab, the potential first all-infant protection against RSV, respiratory sensational virus. Pivotal trial readouts expected in the next few months include the much anticipated recombinant COVID-19 vaccine and AMEERA-3 for amcenestrant in second line and third line breast cancer. The amcenestrant trial is event-driven, now expected to occur end of Q4 or in Q1 based on the latest update on projected event rates. As of now, approximately 90% of the required number of events have accumulated suggesting that we will have data soon. Also in oncology, the event-driven MRAS trial, which investigates Sarclisa in newly diagnosed transplant ineligible myeloma patients, combined with revlimad, Velcade and dexamethasone is expected to read out in the first half of 2022. Initial data for frontline myeloma patients who are eligible for transplant will be shared at a major hematology congress later this year. In hemophilia, FNS Octacoligalpa, our long-acting Factor VIII therapy with the potential to transform replacement therapy for people living with hemophilia A, is expected to read out in Q1. With regards to fitusiran, our first-in-class siRNA targeting antithrombin III that rebalances the deficient coagulation cascade with a convenient subcutaneous small volume injection delivered once monthly or even every other month, we will share data later this year at an upcoming medical congress for patients treated for 9 months with the original 80-milligram dose on a monthly schedule. Seeking to optimize the coagulation rebalancing effects of fitusiran, a lower dose has been recently introduced into the protocol and we will continue to collect data to provide longer efficacy and safety follow-up data for patients with hemophilia A and B with or without inhibitors. Conversations with health authorities continue about the registration requirements. But altogether, timelines have likely shifted by around 18 months. Now moving to Slide 7. If you attended our R&D Day last year, you heard me described Sanofi as an immunology company with strong core competencies in immunoscience that stretch into multiple therapeutic areas, including autoimmune and inflammation, immuno-oncology and hematology. Today, I would like to provide some insights into our work in neuroimmunology with updates on 2 molecules. First, tolebrutinib, the brain-penetrant BTK inhibitor, which is expected to be disease modifying for multiple sclerosis and potentially other neuroinflammatory diseases. We initiated 4 Phase III trials for tolebrutinib, immediately following, achieving proof of concept. I'm delighted to say that despite the pandemic, patient enrollment in this program is progressing well. Earlier this month, we presented encouraging data at ECTRIMS from the Phase II long reach extension program. Those data demonstrated a low annualized relapse rate over the 48-week treatment period, with 98% of patients remaining in the study. These data indicate that tolebrutinib has the potential to slow disability accumulation, and thus bring renewed hope to people suffering with difficult to treat MS. Unlike other non-brain penetrant BTK inhibitors, tolebrutinib has 2 mechanisms: number one, inhibiting B cells in the periphery and in the brain, and number two, inhibiting inflammatory microglial cells inside the brain, which sets tolebrutinib apart from all other BTK inhibitors. Our scientists are continuing to build the body of data showing the impact of tolebrutinib on human microglia, which supports the thesis that brain penetrant, tolebrutinib, modulates neuroinflammatory processes directly within the central nervous system. A second example of Sanofi's emerging strengths in neuroinflammation is found in SAAR 820, a brain-penetrant RIP kinase inhibitor, which targets necroptotic cell death, cytokine release and inflammatory pathways. Besides exploring its potential activity in progressive MS, this molecule has recently received U.S. Fast Track designation for the treatment of ALS. A Phase II study is set to start early next year. With that, I hand over to Bill Sibold. Sanofi's biggest fan of medicines tackling their inflammation, following his experience developing and launching our MS franchise. Bill?

[William J. Sibold]

Thank you, John. Indeed, it is exciting for me personally to see the progress we are making towards practice changing new medicines for MS, ALS and other neurological disorders. Continuing with the theme of translating excellence in immunoscience into transformative medicines, I'll start with an update on Dupixent on Slide #8. Dupixent, our mega brand, delivered an excellent quarter with worldwide growth of 55% and added EUR 500 million in sales compared to the same quarter last year. As Paul mentioned earlier, Dupixent's strong performance in the U.S. was further accelerated by impressive sales growth across other geographies where we continue to expand in our new country markets and younger age groups. In the third quarter, 25% of sales came from markets outside the U.S. Supported by the strong contribution from growth around the globe, Dupixent sales nearly tripled over the period of the last 2 years when compared with the third quarter of 2019. Annualizing at close to EUR 6 billion and well on its trajectory to achieve our greater than EUR 10 billion peak sales ambition, Dupixent, for the first time, the one -- reached for the first time the EUR 1 billion sales milestone in a single corner in the U.S. At the same time, in-office visits remain below pre-COVID levels but are now steadily recovering. While we are executing on the tremendous commercial potential of Dupixent across approved indications and geographies, we remain focused on delivering milestones for future growth, which I will explain in more detail on my next slide. Moving to Slide 9, I want to highlight a number of important achievements since Q2. We have consistently delivered on multiple milestones for growth even during the challenging times of the pandemic. In atopic dermatitis, we have recently announced positive pivotal Phase III results in 6 months to 5-year olds after a 10-month trial acceleration, and we are about to unlock growth beyond the adult population in China following the swift approval of AD in adolescents. In asthma, our second core indication, we continue to emphasize our strong safety and efficacy profile by receiving approval of the pediatric indication in asthma. Encouraged by the recent positive data readouts in CSU, EoE and PN, we are optimistic that Dupixent has the potential to become a new treatment option for patients suffering from the burden of these debilitating and underserved diseases. In 2022, we will continue to execute on the robust clinical development program and our agenda of planned submissions in multiple adjacent type 2 indications, all of which are expected to become future growth drivers. As a reminder, the indications mentioned on the slide, combined, have the potential to address a population of almost 0.5 million U.S. patients, further adding to the greater than 3 million patients already addressable today. Advancing to Slide 10, turning to the other specialty care franchises. We saw good business momentum in the quarter. In rare diseases, our Pompe franchise grew double digit in the period with strong performance across all geographies, primarily driven by patient accruals. In August, we launched Nexviazyme in the U.S., and we are now working on establishing Nexviazyme as the next standard of care for the treatment of Pompe disease in global markets. Nexviazyme was also approved in Japan in September. Strong growth of Kevzara was mainly driven by the inclusion of the interleukin-6 receptor blockers in the updated July WHO guidelines for the treatment of patients with severe or critical COVID-19. Kevzara is not approved or authorized for emergency use for the treatment of COVID-19 anywhere in the world, and we will continue to prioritize access for indicated patients with rheumatoid arthritis. As a result of the continued increase in worldwide demand for IL-6 receptor blockers, supply is expected to be constrained until early 2022. The uptake of our new oncology portfolio is progressing well with the launches of Sarclisa and Libtayo. For Sarclisa, we saw strong performance, particularly in Japan, France and Germany. The highlight of the quarter was the presentation of the Phase III trial of Libtayo combination data in patients with first-line advanced non-small cell lung cancer with a submission planned for later this year. Rare Blood Disorder grew 7% when excluding the industrial supply sales of hemophilia products to Sobi. Strong sales growth of Cablivi from new country launches in Europe was the key driver for the franchise in the quarter. With that, I hand over to Thomas to update you on the Vaccines business.

[Thomas Triomphe, Executive VP & Head of Sanofi Pasteur]

Thank you, Bill. In the third quarter, vaccines reached a new record with EUR 2.4 billion in sales, the highest quarterly sales in our history. This strong Q3 performance was largely driven by our Influenza franchise. In the U.S., thanks to our newly licensed facility producing glucosidase, we were able to ship larger quantities in a record time. Europe grew 88% due to successful Efluelda expansion, mainly resulting from STIKO recommendation in Germany. Efluelda is also recognized by the European Center for Disease Prevention and Control as superior to standard influenza vaccines. Let me also share good news regarding nirsevimab, our investigational long-acting antibody under development with AstraZeneca, which is designed to protect all infants for the first RSV season with one single dose. During the IDWeek Congress, we presented the positive results of the MELODY trial. In this pivotal Phase III study, a single dose of nirsevimab showed a 74.5 reduction in lower respiratory tract infections caused by RSV and requiring medical care in healthy infants. The safety profile of nirsevimab was favorable and similar to placebo in these infants. We will share more data on the safety results of the MEDLEY study, for which we already announced similar safety and tolerability compared to palivizumab at the ResViNet conference in November. So stay tuned for more exciting data on nirsevimab. Moving on to Slide 12. It's important to remember that evidence accumulated over 10 years has demonstrated year after year that Fluzone high-dose Efluelda provides protection beyond flu, which means protection against cardiovascular events as well as protection against pneumonia hospitalization. This extensive body of evidence is clearly the driver of our flu franchise success. In Q3, our differentiated flu sales amount to close to EUR 900 million and represent 2/3 of the total franchise sales when it was less than EUR 400 million just 2 years ago. This quarter, we launched a new DTC campaign in the U.S. to communicate the unique benefits of Fluzone high-dose, and we are very glad to see that other healthcare partners have recognized the superiority of this product, as illustrated by the Walgreens communication on the right side of the slide. To conclude with flu. We recently announced our modifying AMEERA [indiscernible] flu vaccine in the clinic in 2022. For this new program, the benchmark in terms of clinical benefit for the elderly is Fluzone high-dose as it is becoming the standard of care for seniors. Simply demonstrating immunogenicity versus regular influenza vaccine will not be sufficient in this fast-evolving market. Let's now look at Slide 13, and talk about Sanofi COV19 vaccine program, developed with the adjuvant of our partner, GSK. The upper part of the slide describe the ongoing Phase III safety and efficacy study conducted over 4 continents. Now that the enrollment stage of Stage 1 part of the study, testing a 10-microgram dose of the parent strain is about to complete, we do expect to have our efficacy readout by year-end when we have accrued a significant number of cases -- a sufficient number of cases. In parallel, the enrollment of Stage 2 of the study, testing a bivalent formulation of 5-microgram parent strain and 5-microgram beta strain has started this month. Let's now turn on the booster study at the lower part of the slide. It will assess the immune response in adults previously immunized with the vaccine using either mRNA, protein or adenovector technologies. The first arm of the study is testing a 5-microgram dose parent strain, and we do expect key data to also be available by year-end. As previously mentioned our aspiration is to develop a practical universal booster vaccine. They are more stable at normal refrigeration temperature and agnostic to which vaccine technology was previously used in the primary series. With that, I now hand over to Olivier.

[Olivier Charmeil, Executive Vice President of General Medicines]

Thank you, Thomas. Moving to General Medicine on Slide 14. We are very pleased with our performance in the third quarter. The execution of our strategy continues to deliver, and the focus on our core assets has generated consistently positive results in recent quarters. General Medicine sales reached EUR 3.6 billion, with our core asset up 5%, supported by the solid performance of the cardiovascular and diabetes brands in our portfolio. We saw demand driven strong double-digit growth of Toujeo and Soliqua across most geographies in the quarter, while Plavix growth of 6% was mainly due to higher volumes in China where the product is included in the VBP program already for the second year. Praluent sales increased strongly, mainly as a result of the performance in Europe. And due to the ongoing launch in China, when you exclude the effect of Praluent sales to Regeneron in the U.S., which ended beginning of 2021, the brand grew 64% in the quarter. Lovenox, our largest core asset by sales, grew 4% and continued to benefit from inclusion in WHO guidelines for the treatment of hospitalized severe COVID-19 patients. As highlighted last quarter, growth of Lovenox started to slow in the period due to the high base of comparison in the third quarter of 2020. We expect sales will slightly decrease during the remainder of the year. Sales of noncore assets of the General Medicine business were lower in the quarter, in line with expectations. It's a decline of 6% reflected the impact from divestiture of products which are part of our ongoing strategic portfolio streamlining efforts. We are consequently reducing the number of smaller product families, with the objective to drive efficiencies and to increase profitability. I will provide more insights into reducing the complexity of the portfolio in just a minute. Now on Slide 15, Paul has already mentioned a compelling strategic fit and strong rationale of the announced Kadmon acquisition. Transplant is a well-established growth area for our General Medicine business, driven by expertise in this market and anchored on our core assets, Mozobil and Thymoglobulin. Both brands reported solid growth in the last 9 months, up 14% and 16%, respectively. The acquisition of Kadmon adds a significant growth opportunity for us and builds on our experience in this transplant arena, where we intend to further expand our robust commercial presence with a complementary portfolio. You will have seen that Kadmon's key asset, Rezurock, was approved by the U.S. FDA early this summer. It is a first-in-class treatment for adults and pediatric patients, 12 years and older, with chronic graft-versus-host disease, who have failed at least 2 prior lines of systemic therapy. Steroids are the current standard of care in frontline chronic GVHD treatment, but roughly half of the patients are estimated to fail on steroid therapy. While later lines of therapy and also additional efficacy, adverse events mean patients often fail to tolerate. Rezurock puts in Sanofi's hands with an established and leading transplant expertise, we believe we can get it to more patients faster. Initial market feedback has been very positive. And we anticipate to close the Kadmon deal soon in November, subject to approval by Kadmon stockholders. The expectation is that the deal will be accretive in 2022. On my Slide 16, I want to highlight the process we are making on our -- the progress we are making on our commitment to transform our General Medicine business through streamlining the tail portfolio of established products as well as reducing our geographic footprint and simplifying the go-to-market model. On our path forward, a more resilient and a more profitable General Medicine business, we have been steadily reducing the number of nonstrategic product families over recent years, mainly through divestitures. These streamlining efforts have resulted in almost EUR 1 billion of cash proceeds. To reduce the complexity of our business, we have already drastically reduced our footprint in nonstrategic markets and transferred distribution activities to third parties covering already more than 40 countries. We are also making significant progress in advancing on our digital transformation. Digitalization of healthcare has been accelerated due to the pandemic. We are engaging with doctors and patients through our omnichannel approach, which leverage our increasing capabilities in data, digital and AI, positioning Sanofi as a preferred partner to HCPs. More than 60% of our HCP interaction are now supported by digital platform compared to only 30% in 2019. To conclude, we are making solid progress with implementation of our strategic priorities, which keeps us on track to deliver on our objective. With that, I hand over the call to Julie.

[Julie Van Ongevalle]

Thank you, Olivier. Following a return to growth last quarter, I'm very glad to report continuous growth in the third quarter. It's the result of good performance from all geographies and almost all categories. These positive results show that the execution of our strategic road map is starting to deliver. I want to specifically highlight that on cutting and embracing complexity, we've been successful in our simplification effort. Knowing that out of our 250-plus brands, we have already discontinued the production or announced divestments for 111 brands or 45% of our brands. We're also continuing our simplification endeavour at many other levels to further increase our focus on our priorities. At the same time, the prioritization of our wellness categories continues to pay off, with the Digestive Wellness brands, Enterogermina and Buscopan, performing very strongly as well as our magnesium brand in mental wellness. And in Q3, the good performance of pain, we received an additional boost with consumer purchasing Doliprane and Eve while getting their COVID-19 vaccination. Lastly, I'm pleased to report that cough and cold is back to growth, although from a low 2020 base. On our second strategic priority of becoming a true fast-moving consumer healthcare company, the creation of our stand-alone is a key business enabler. And I'm happy to report we're progressing as planned with more than half of the legal entities created as of today and with the next significant wave expected on January 1, 2022. More importantly, we are already seeing great benefits of the progress made to date, allowing our teams to adapt new processes, policies and overall ways of working as a result to move faster and be more consumer-centric. We've also been able to successfully reallocate A&P investments to our must-win brands and countries to accelerate growth. As a conclusion, you might remember that historically, our GAAP versus market growth has been substantial. In 2020, this gap was close to 5 points. On a rolling 12 months, we have reduced this gap to less than 2 points, and I'm very happy to share that year-to-date, we divided this gap by 4 to lessen 0.5 point. With that, I hand it over to our CFO, Jean-Baptiste.

[Jean-Baptiste Chasseloup de Chatillon]

Thank you very much. Thank you Julie. On Slide 18, turning to our financial performance. Company sales increased 10.1% in the third quarter, driven by excellent growth of Dupixent differentiated flu on consumer health. We said we would be improving on our gross margin and we are delivering based on the favorable portfolio shift to specialty care products and efficiencies within industrial affairs. This quarter, the vaccine business contributed also strongly to the improvement of more than 200 bps due to partial recovery of the meningitis vaccine business in the U.S. We are committed to science and our R&D spend increased during the quarter, driven by advancements of our priority assets. We also continue to add R&D spend from recent acquisitions. In SG&A, spend was driven mainly by commercial investments behind Specialty Care, growth drivers on flu vaccine, partly offset by continued streamlining of G&A. Other operating income benefited from net gains from disposals of around EUR 130 million versus around EUR 60 million last year, contributing to a BOI margin of 34.1% in the quarter. Adjusting for this in both years, BUI clearly outgrows else. On Slide 19, we have achieved around EUR 2.1 billion of cumulative savings, EUR 2 billion in OpEx, as shown on this slide, but also EUR 100 million in COGS. We already achieved our target of EUR 500 million savings in R&D due to prioritization of Specialty Care and exiting diabetes and cardiovascular. In addition, permanent efficiencies were generated by consolidating functions across sites, improving our trials logistics and reducing cycle time through a more agile governance. In the same period, spending in R&D increased by EUR 500 million behind our priority assets and due to recent acquisitions such as Principiacimab and Tidal. We have a similar picture on SG&A, where we invested around EUR 1 billion more behind our growth drivers in Specialty Care and Vaccines. This was partly offset by permanent savings achieved in GenMed as explained by Olivier as is decomplexifying the business, focusing on key markets and employing a digitally enabled go-to-market model. General and administration across all areas of Sanofi contributed until H1 2021, EUR 400 million through smart spending initiatives, real estate efficiencies, preferred supplier model and digitalization. So we remain -- we are on track to achieve our target of EUR 2.5 billion savings by 2022, with most of this years and next year savings to be reallocated behind our growth drivers on key programs in R&D. So on Slide 20, we summarized expected dynamics in Q4 of 2021. So for pharma, we expect continued growth from Dupixent, GenMed core assets are expected to grow with Lovenox returning to stable. Divestures will have a negative effect on established products. The latest round of China VBP will be implemented late Q4 this year and uncertainties remain around the future mechanism for insulin class inclusion. For Vaccines, we expect Q4 sales to be in line versus last year, with flu vaccine sales growth driven by Europe, compensated by continued weakness of travel vaccines on lower U.S. PPH sales following the Vaxelis launch. We expect Consumer Health to grow in line with market in Q4. And OpEx will grow, especially with the impact on R&D of TBIO and potentially Kadmon closing. So Slide 21, based on the strong results during the first 9 months of this year, we are raising our full year guidance for 2021 business EPS. We now expect business EPS to grow around 14% at constant exchange rate. The outlook regarding foreign exchange impact continues to be negative by minus 3.5% to minus 4.5% based on October average exchange rates. And with that, I hand the call back to Paul with an important update on our ESG road map.

[Paul Hudson, CEO & Director]

Well, thanks, J-B. Today, we announced our ambition to strengthen our commitment to the planet, with the target to reach carbon neutrality by 2030. This marks a 20-year acceleration versus our previous targets. We're building on great work done across the organization that has allowed us to already reduce emissions of our activities by 27% since 2015. Most importantly, we now introduce our net zero target by 2050. We will take the opportunity of COP26 to set up common initiatives within the industry. Let's have a quick look at a few key initiatives we're rolling out. We have set the clear ambition of 100% renewable electricity across our operations by 2030. We are moving full speed ahead and delighted to highlight that all our sites in France are now entirely powered by renewable electricity. We're taking decisive actions to reduce the environmental footprint of our products. As an industry-leading global manufacturer of hundreds of millions of vaccines every year, we have made recyclable eco-friendly product packaging a priority, with the aim to reduce blister free vaccines by 2027. We've reached the first milestone with approximately 25% of all flu vaccines packaged in sustainable materials already this year. The pharma industry itself is heavily regulated, and it would be easy to hide behind complex supply chains, interactions with regulators and regulatory agencies, et cetera. But the reality is that climate change is already here. So the time for sustainable action is simply now. With that, I think it's time to open up for Q&A, and I hand back to Eva.

[Operator]

[Operator Instructions] And now we will take the first question from Simon Mather at Exane.

[Simon Mather, Pharmaceutical Equity Analyst]

I've got two, please. One on the outlook. And secondly, on amcenestrant. I mean, firstly, you delivered a very strong operational execution once again for the quarter. And if you look at 9 months, you've already exceeded your 2022 BOI margin target of 30%. And this quarter significantly exceeded your 30% 2025 target. I'm just wondering, can you help us understand why we shouldn't assume upward pressure to both the near and midterm targets, especially considering previous comments that you've made that Dupixent is going to be margin accretive in 2022? I guess with that, is there anything specific you put -- you call out for 2022 in terms of push and pulls that we need to take into account? And then secondly, on AMEERA-3. There's the recent data from Menarini's Emerald trial increased your level of optimism around a positive outcome given the similarities in the 2 trial designs. Can you just take the opportunity to remind us of the key differentiating factors of amcenestrant versus the competitors in your eyes, please?

[Paul Hudson, CEO & Director]

Simon, I'm not sure it was 2 questions, but we'll do our best. I think -- and thank you for kicking us off. J-B, so the question, of course, on BOI, we're tracking ahead. What does it mean for now and onwards to 2022 in the guidance that we've already given? And I think it would be good for you to share your view.

[Jean-Baptiste Chasseloup de Chatillon]

Yes, Simon, thank you very much for your kind words about our operational execution. And I think you're perfectly right to think that there's no operational reasons to change that trend. As there is no reasons to change our -- the way we manage as a company, which is really each time we can, why we are respecting the guidance for 2022 and 2025, we take the opportunity to add to the science, to add to our pipeline. And you see what we are doing with TBIO, we see what we are trying to do with Kadmon. I mean all of those operations, we aim to go on each time we have room to do it. So it's not about beating expectations on our BOI margin guidance, it's really about reallocating from our cost savings into the science to augment the valuation of our pipeline. We are really -- it's very simple, and we have not changed since December '19.

[Paul Hudson, CEO & Director]

Yes. Well, so JB, I mean it's the truth. We gave you some guidance for 2022, 2025 should look like. And we get ahead, we can create a ton of value by accelerating or doubling down on our own science we're adding. So it's a great position to be in, to be honest. John Reed, a comment on AMEERA-3 and -- which I think you've already sort of said, but then more importantly, the data from, I think it was Menarini and Radius and what that means?

[John C. Reed]

Yes, Simon, thanks for the question. Indeed, the positive results for elacestrant does increase our confidence in AMEERA-3 because the field was really lacking robust data from a CDK4/6 experienced patient population. And now we have it through those data. We'll look forward to the details of the data at the San Antonio Breast Cancer Conference, but that is encouraging for our study. And even more so, I think, because elacestrant seems to have a preference for the mutant form of the estrogen receptor, and not so active against the wild-type form, whereas our molecule amcenestrant is equally active against both forms. And of course, the safety profile is really best-in-class for amcenestrant, whereas the Radius compound has a history of grade 3 safety events. So we're even more bullish, I think, after seeing those data.

[Operator]

The next question is from Pete Verdult at Citi.

[Peter Verdult, Managing Director]

Pete Verdult, Citi. Two topics that usually don't get much airtime, despite being 50% of sales, Consumer and GenMed. Julie, just following up from your prepared remarks, I mean, if you were to characterize Q3, how much of it is just a function of easy comps versus clear evidence of the measures that you put in place coming through? And when you -- I think you hinted at this, but it sounds to me that you believe the Sanofi consumer business can deliver or can get back to industry-leading growth in 2022. Just wanted to sort of kick the tires there. And if you could, very quickly, just remind us what the timelines are that you're working to for these Rx to OTC launches on Cialis and Tamiflu. And then something similar for Olivier. Again, I noted in your prepared remarks, but can I just push you on VBP insulin ballpark quantification of the likely impact. And then on Rezurock, lots of enthusiasm. Consensus for Kadmon was about EUR 1 billion. Is that something that you feel is fair? Or do you internally, at Sanofi, have higher expectations in terms of the peak sales expectations for Rezurock?

[Paul Hudson, CEO & Director]

Okay. Good. Good. We're really getting into it. Julie, how much of it is favorable comps, I think, generously said? And how much of it is just sheer excellence in execution, which bodes well for the future?

[Julie Van Ongevalle]

So first, Pete, thank you for your question. I think our growth is really coming from 3 sources. Yes, there is an additional boost of COVID vaccination in pain specifically, but basically representing only 40% of our pain growth. Some categories, there is a low base. Some other categories, there is a very high base, right, talking about cough and cold. And also, as I mentioned earlier, indeed, clearly, improved brand activations resulting from increased consumer centricity already, which is, for me, a key component of our strategic road map and also a guarantee for our future success. So when you asked about lots of questions, actually, our future growth and outlook for next year, I mean, our goal is to continue to reduce our gap versus market as we also shared at Capital Markets Day, and I shared earlier and grow our priority brands really above market as early as 2022, so as early as next year in key geographies, again, by delivering our strategic priorities, which are -- I mean we have multiple proof points. And I think you had -- there was another question?

[Peter Verdult, Managing Director]

The Rx to OTC switches timeline, just lay some of the timelines.

[Jean-Baptiste Chasseloup de Chatillon]

Well, I'll pick that one up before we hand to Olivier. But I wanted to jump in because I want to say it's quite extraordinary the transformation that's going on in the consumer business, and I feel like it's gaining momentum, and it's got strong staying power, what's going on. So I know you paid close attention to that, but it's really cool. Most stuff you don't see, but you'll see it in the numbers at some point. The switches, not much has changed. It's around the middle of the decade, I think, because we talk about Tamiflu and Cialis roughly around about the same time. One little nugget that I think as -- we haven't shared yet is that we've completed one of our self-selection studies successfully, and it's just the digital piece upfront. We've got another one to go before we get talking to the regulators again. But as steps go, we continue to make good progress behind the scenes. So now that we have a ways to go, of course, we've never said anything other than that. That was a good little milestone for us to show that we know how to do these things. Of course, there's a lot to happen between now and then, but we were pleased to get that first step. Olivier, so over to on VBP incident.

[Olivier Charmeil, Executive Vice President of General Medicines]

So Peter, thank you for your question. We had said that, of course, in our plan, we had incorporated the insulin VBP impact starting in 2022. So although the policy has not yet been fully disclosed and will probably be released in the course of the months of November. And we are expecting the bidding process to start either at the end of November or beginning of December for an implementation that is going to start in H1 2022. So really no surprise in line with our expectation. I would add that we are very happy with the continued performance of Plavix that shows our ability to grow volume, not only the first year, remember 91% for Plavix the first year after implementation of VBP. But also, we continue to grow on a nice pace. And we continue to think that especially in the field of diabetes, there are still a lot of potential to grow our volume. With regard to your question with a -- on Rezurock, we are very excited by Kadmon. We hear very positive anecdotal feedback coming from key opinion leaders. We are expecting as a closing to take place further to stockholder approval beginning of November. We are very much looking forward to be in the field. And when we look to the upcoming years, 2022 is going to be a very exciting year, and I can tell you that we think that in 2020, the -- Rezurock is going to be relutive and we are very much looking forward to enter 2022 for Rezurock.

[Jean-Baptiste Chasseloup de Chatillon]

Not expecting it to be dilutive in 2022. I will say -- and it's worth timing, Pete, what we've done, and we mentioned a few times front in my comments, but you heard me mentioned Capital Markets Day 2019 a few times because we're trying to keep delivering on our commitments and promises even when we're anticipating quite far ahead. I think we're doing that really brilliantly actually. But Feb 5 was the other landmark for us. It was the consumer and GenMed, and of course, immunology piece. But on consumer and GenMed can be equally effusive about transformation that's underway in GenMed. I think we're just underappreciated what we're going to be able to do on such a large piece of business. I think you said it's nearly half our revenue at the upfront of your question. And frankly, the work that's being done and the breakthrough work gives us huge confidence in what we have ahead of us and fueling everything else that we're doing. So delighted with that.

[Operator]

The next one is from Wimal Kapadia at Bernstein.

[Wimal Kapadia, Research Analyst]

So first, can I just ask about the anti-CEACAM5. So maybe it's a little bit of an unfair question. But typically, when a target that looks highly prevalent across multiple tumor types, you would see several players focused on the target despite the failures with some of the failures we've seen. So is this Sanofi being ahead of the competition? Or is it because of the strength of the molecules? So just curious to hear your thoughts there. And then just tied to that, how do you think about the potential competition from the TROP2 target with respect to the anti-CEACAM5? And then my second question -- sorry, I can't pronounce the name, so I'm just going to say BIVV001. Just in terms of efficacy, should we expect to see a better clinical outcomes versus existing Factor VIII? Or is duration of usage the most likely key advantage? And then just on commercialization, how should we think about the launch trajectory? And just given the stickiness of patients versus the previous Factor VIII launches, but now it's been several years. So maybe there's a little bit more appetite for switches versus the past? So just curious to have your thoughts there as well.

[Paul Hudson, CEO & Director]

Loving it that we're getting into the pipeline conversation. So Jean, maybe tusamitamab, we're ahead of everybody else and as it compared to the other mechanisms with similar targets?

[Jean-Baptiste Chasseloup de Chatillon]

Yes. We are -- the -- that class of targets, the CEA, carcinoembryonic antigen is complex. But fortunately, our scientists really were able to focus on a variant CEACAM5, that is very tumor-specific in its expression, scarcely expressed in any normal tissues. And that really, I think, turned out to be the key attribute here of the molecule that's allowed us to succeed where perhaps others had not. So we're very excited about the current molecule, and I think we've also shared that we want to do more with it and put different payloads on that molecule for different kinds of cancers. So we're very eager to generate the data around that. We will, next year, have I think 4 Phase II studies that will deliver data next year, including in gastric cancer, including a combo study in lung cancer together with ramucizumab, Cyramza, including data in breast and pancreatic as well as some data in frontline lung together with a PD-1 inhibitor. So next year will be a rich year for some readouts while we continue the Phase III journey with the pivotal study. And in terms of the comparison with TROP2, we like this better than TROP2 because according to our data, TROP2 is not as clean in terms of expression in normal tissues versus tumor tissues compared to CEACAM5. So we think our therapeutic index will be superior.

[Wimal Kapadia, Research Analyst]

Thanks, John. Maybe, Bill, you comment on efanesoctocog or BIVV001?

[William J. Sibold]

Why don't we just call it EFA? That makes it a lot easier for me, I guess, certainly tell you that. But we're really, really excited about it. And this is not only going to bring longer dosing interval, but a degree of higher protection. And I'll just -- from the September 2020 New England Journal of Medicine publication, it was there that it was referenced as a potential new class of Factor VIII replacement therapy with a weekly treatment interval that would transform severe hemophilia A into a mild disease. That's the promise. This is a game changer in hemophilia A. We believe there is no reason that anyone who's on factor isn't on EFA. That's how good it is. It's going to get people back to a more normal level. So yes, we're really excited. Now there's been a lot of change in the market, obviously, with different mechanisms coming in, which increased the switch rate. That slowed down a little bit during COVID 19. We expect, though, and a lot of the market still remains a factor market. We're excited about getting EFA out there and really seeing it becoming the leading factor.

[Operator]

The next question is from Geoff Porges at Leerink. Geoff? Okay. So in the meantime, we can take -- okay. Yes, we can hear you now.

[Geoffrey Craig Porges]

First of all, I just want to say congratulations on making the commitment on climate change, Paul. I think that's pretty impressive and encouraging. So a couple of questions. First, on rilza. Paul, could you just give us a sense of -- John, sorry, could you give us a sense of what you saw in the rilza pemphigus data? Because you're pretty clear that the primary and secondary endpoints were not met. But now you've announced additional studies. So is rilza something that we should see as a future value driver and contributor or not? Could you help us understand that? And then secondly, on Dupi, you're annualizing at EUR 6 billion a year right now. You're growing at better than 50%. It looks like you'll hit the EUR 10 billion target in about 18 months if that growth continues. You've got 3 new indications. You're just getting started around the world. And yet the Street really is tethered to that EUR 10 billion number call. Are you willing to update it? And why isn't that $15 billion or $20 billion?

[Paul Hudson, CEO & Director]

Okay. Great. Great questions indeed. Thanks for the comment upfront about climate change. There's a lot of responsibilities come with this -- for the role that I have. And one of the privileges of being here is that he's got a company that perhaps not well publicized, but was doing an incredible amount to -- in the benefit of our contract with society. We're doubling down in a few places, we're excited about that. We've declared some other shared industry perspectives at COP26, which is not that far away. But we have an absolute responsibility, as I said, upfront to do something. And it's not just for a poster by the elevator, it's real work being done by a whole organization on a daily basis. So really proud of the organization. A long way to go, like everybody. A long way to go, but really proud. John, rilza, I think you touched on it upfront. Maybe there were some factors in the placebo arm, other treatments and things like that. But to be candid, we -- how do you feel about how we performed? And what the opportunity could be around the corner?

[John C. Reed]

Yes. Thanks for the question, Geoff. The -- in that study, there was a background glucocorticoids, high levels of those that patients were on -- in both the placebo and the treatment arm. And then one of the -- it was a complex endpoint, but part of it was how quickly can patients get to lower dose of steroids. And we saw a couple of things. One was that the response rate in the placebo arm was 3 to 4x higher than has been seen in any other PV study. So evidently those high doses of glucocorticoids in the control arm really interfered with the ability to see the signal. Also the trial, which we inherited from Principia, was ongoing when we bought the company. The criteria for physicians, treating patients on the study in terms of determining what threshold would meet the requirements for reducing steroid doses were not very strenuous. So there was quite a bit of heterogeneity in terms of when physicians decided to titrate down steroids, background steroids. So -- that and some other lessons learned from the study lead us to believe that we could have had a better design study. And at that indication, we would have approached it in a different way going forward. As I said, the other data we have coming from ITP, though, on the other hand, is very encouraging. So that boosts our confidence that the molecule has merit. Those data showed a good response rate, a very competitive response rate, excellent durability as well. We're in the Phase III. It's progressing well. We'll have an opportunity to share details of the Phase II data at upcoming congresses as well as in a publication. And we are pursuing rilza and other indications. So we have high hopes that, that molecule, given the importance of the BTK target across a number of autoimmunoallurgic diseases, will be a big player in our portfolio on a go-forward basis.

[Paul Hudson, CEO & Director]

Thanks, John. Bill, it's a question we're getting a lot. So it'd be good to share your view -- our view on potential peak for Dupixent.

[William J. Sibold]

Well, first of all, Geoff, thanks for the question and for the stats that you gave leading into it. It's really been impressive what we've been able to do. And in the last quarter. It's been incredibly impressive as well.Just since Q2, we've had 6 milestones, which is just really an unbelievable pace which we're going. And the thing that I find really reassuring is this is a global brand truly with 25% of the sales now coming from outside of the U.S. And it is not a U.S. product by any means, it is a global brand.Now if you look towards what was in that $10 billion plus forecast that we gave, COPD wasn't in that. So naturally, we -- you may think that after we announced that in 2023, it would be a time to change our guidance. But given the rocket ship performance and the distance to 2023, we think it is important to update prior, and we're currently discussing the timing of that. So I would say stay tuned for the moment.

[Operator]

The next question is from Graham Parry at Bank of America.

[Graham Glyn Charles Parry]

Can you hear me, okay?

[Paul Hudson, CEO & Director]

Yes.

[Graham Glyn Charles Parry]

Brilliant. So I'm going to follow up, John, on AMEERA-3. If you can just remind us when recruitment was complete? And so how long are -- you actually have you had patients on drug in that study for now? And to what extent do you see it as an encouraging sign that you're taking longer for accrual events? And does it change your statistical analysis plan at all? And John, on the second quarter call, I think you said that just looking at how events are accruing, you're looking at 4 to 6 months' PFS. I just wondered, was that for all patients? Or is that referring to the control arm or the drug arm in the study? And then a second question for John. Investors often say to us that post AMEERA-3, there's not a lot going on in Sanofi R&D until 2023. So perhaps you could just help us with what data in 2022 you're almost looking forward to?

[Paul Hudson, CEO & Director]

Graham, I'll hand it to John. Nobody has seen any of the data, right? We're -- the difference, of course, since Q2 is we're excited because we've seen the Menarini and Radius data. So that's a good indicator. But we haven't seen any of the data. The only thing that we've shared, in fact, is that 90% of the events have been accrued. We haven't even declared how many events we're actually expecting to see. So John, I don't know whether you want to add anything, but I'm not sure there is much, but I'll leave it to you.

[John C. Reed]

Yes. I don't know that there's a lot more to add. One should always be cautious about over interpreting the fact that an event-driven study is continuing on and on. We'll just have to wait for the data. We're not planning, at this point, to change the statistical analysis plan. But we'll take a look at what we learned from the data of Radius when they presented at the San Antonio meeting and see if there's any second thought we have around that. But right now, we're staying the course and waiting for the events. And as I said, 90% of them approximately have occurred. So we -- hopeful in the next few weeks that we may get there. So yes, I think we all just have to remain patient while we wait for the curtain to open here and to see -- turn over the card here. In terms of events for next year, gosh, there's a number of things that we could be excited about. I mentioned some of the front lines. There will be frontline data for Sarclisa next year with the most modern backbone therapy that will be an important opportunity for us to move into the frontline space with -- and see if we continue to demonstrate a best-in-class profile among the CD38 class in myeloma. So far, 2 out of 2. There's going to be more data presented at an upcoming congress at the end of this year, which will give further insights. So I think that's certainly something we'll be watching. I mentioned there will be some Phase II readouts on tusamitamab in additional indications or in combinations with other medicines. So I think that's going to help further establish the level of excitement to have in that molecule based on what we see in those studies.Data will be trickling in for SAR'245, our non-alpha IL'2 throughout the year next year. We have started in 4 indications at least now. And so those data will be accruing in the signal-seeking studies across dermatology across lung, across GI and head and neck cancer. So we'll be getting more and more insights into that molecule in combination with PD-1. efanesoctocog was mentioned. We're going to have the readout on that next year. So that's really exciting. So those are a few off the top of the head. We can refer you to the backup slides that show all the readouts next year, and we think it's going to be a good year for us.

[Paul Hudson, CEO & Director]

Thanks, John, for that summary. That list is getting longer, I noticed. The -- I just want to come back -- so no misunderstanding from anybody on AMEERA-3. Never seen any data. We're 90% accrued. We've been confident throughout the process. We believe in the pathway. We have a great meds. some of the great balance of safety and efficacy. And the recent data from Menarini and Radius gives us even more confidence. So we'll turn the cards over. As always, that's our game. But we're optimistic about turning them over. So let's see where we get to, right?

[Operator]

So the next question is from Matt Weston at Credit Suisse.

[Matthew Weston, Managing Director and Co]

Two questions, please. Sticking with the pipeline. Firstly, on fitusiran. It's had a checked history. We've now got an 18-month delay to the readout. Is there anything that we'll see between now and 2023, '24 that will allow investors to understand your continued optimism for the molecule? And then just a quick one on the COVID Universal Booster strategy. Can you tell us whether now the pricing for that program if it's profit -- if it's positive, apologies, would be for profit? Or whether it would remain one where you would aim for not-for-profit pricing?

[Paul Hudson, CEO & Director]

Okay. Matthew, thank you. I'll toss it to Bill. Fitusiran, but since I joined the company, I've been -- we did a lot of diligence in the company in the early days when I got in-house I was able to see the data. And I was always excited about fitusiran. Of course, we've seen what Hemlibra had done. We saw how fickle the market was. How quickly it would move. We look ahead at what fitusiran will compete, even with the delay. And as a management team, we look at that and go, "Can we still thread the needle on an exquisite profile?" And we know that we will have to go to a lower dose probably, and we'll experience that. And we also know that our interval could stretch further. So -- and there isn't that much excitement in follow-ons from other companies. So -- it's a needle to thread, but if we get it done -- that's why we stick at it, I think we can really make ourselves a very successful medicine here. So I'm -- it is one of those things where I think we are a little bit a ways from where we need to be. But we keep making progress. We keep learning. We're excited about the profile. And at every turn in any data we picked up, there are patients that have responded like they're living disease-free. So we know that we just have to balance those things. And that journey so far is still worth the trade for us, and we feel our way to this point. I don't whether John or Bill want to add anything else?

[William J. Sibold]

Paul, just to echo all your comments. Look, this has a really unique profile, whether you're looking at any gene therapy or anything else, a potential every other month, so 6 injections per year. It's a great profile, small subcu administration. So let's see, I think John mentioned in his statements at an upcoming meeting this year, we'll be reporting out some of the 80 milligram dosing. So stay tuned.

[John C. Reed]

Yes, that's right. You're asking what data or what we might be able to provide the investor community to help understand why we remain excited about the asset? And indeed, there will be a presentation of data at an upcoming congress later this year and probably into next year as well. We have the full data set on the original 80-milligram q monthly dose for the 2 main Phase III studies, one of those with patients with inhibitors and the other was without. So those data will be shared with the community in the next few weeks and months. And then we go from there and further with the studies we're doing now to explore the lower dose in the more -- the less frequent dosing intervals. The one thing I would just say, because this is an sRNA drug, we have to all remember that, that class of drugs is nontraditional pharmacology, right? They have what I would call a depot like effect. And doing some titration of that is perhaps not unexpected. We know what levels we have to hit antithrombin III reduction to hit that sweet spot, and we're just dialing into that right now.

[Paul Hudson, CEO & Director]

Thank you, both. Thomas, Boosters?

[Thomas Triomphe, Executive VP & Head of Sanofi Pasteur]

Thank you, Matt, for the question on COVID-19 boosters. Let me start quickly by saying that our strong engagement on the COVID pandemic is not about the financials, be it for the COVID-19 booster or for the very often under reviewed 500 million doses of vaccines that we're manufacturing from 3 different manufacturers on top of our own development.Now back to your initial question. As we commented before, it's clearly going to be an affordable pricing. And we have not changed away from that at all. That's the strategy. So we've already said before, it will be a sort of EUR 10. No change there. Now it's up to the Phase III readout that's coming pretty soon.

[Operator]

Yes. So I'm going to take the next question from the chat. Luisa Hector from Berenberg. The first question on Dupixent, it's actually a 3-in-1. Can you provide the U.S. sales split by indication? How is the China launch progressing? And you continue to note fewer in-person physician visits in the U.S., so you remain slightly below pre-COVID. When do you expect this to normalize? And the second is on flu COVID combo vaccine. Do you continue to believe that demand for such a combo would be low? Or are you positioned to move forward on this despite ending your COVID mRNA development?

[Paul Hudson, CEO & Director]

Okay. Good, good. I counted 4 questions, but okay. Bill sales split, I'm not sure, frankly, how much we share on that beyond the geographies that you've already shared? And China update in-person visits numbers, of course. And then Thomas, I'll come to you for a quick comment in a moment on flu and COVID.

[William J. Sibold]

Yes. So thanks for the question. Maybe starting in the reverse order there about pace of opening. And we were encouraged actually to see between last quarter and this quarter trend up closer to 85%. And that varies obviously by specialty. As far as when does it get back to normal, it's really a question of COVID, right? If we can predict that, we can predict when we're going to open up. And again, we think that we see some really encouraging signs. I will just reiterate that not all specialties were affected the same through the pandemic as it relates to Dupixent. We saw with pulmonologists and any of the respiratory physicians that it was -- they were harder hit. Oftentimes, we had pulmonologists being pulled into ICUs and so forth to take care of patients there. And also patients with any respiratory illness because they were so susceptible, we're really kind of hunkering down at home. So you didn't see the same exacerbation rates, et cetera. And I think that reads through in asthma as well as COPD as well. So just a little bit of context there. We're not going to break out the indication split within the U.S. or anywhere for that matter. But I can say that there is strong growth across all the indications. You had a specific question about China. And we've been really, really impressed with the work that the team has done in China since getting the NRDL listing in March. And this is tracking to be one of the most successful immunology launches in China ever.And as we've stated, we think this is going to be a blockbuster in China on its own and will become a real leader in I&I. In the next 3 years, the labeled population in China will expand children AD 6 to 11 in 2022, but then we also expect infant AD in 2023 and asthma in 2024.So we really are at the beginning with Dupixent in China. So we're building a strong foundation, a strong base. We're accelerating hospital listings. We're doing policy shaping. We're growing the number of prescribers, and we're really accelerating access to patients. So this is a long-term story. It's off to a great start, and we look forward to reporting more on it in time.

[Paul Hudson, CEO & Director]

Well said, Bill, thank you. Thomas, flu/COVID approach?

[Thomas Triomphe, Executive VP & Head of Sanofi Pasteur]

So your question is about the flu COVID-19 combination interest need versus clinical profile? For any combination, and you know that we know commissions fairly well as we are the worldwide leader of perfect combinations. We're always looking at what's the need for it, what problems are we trying to solve versus clinical benefit. In terms of need, we always look at what's the convenience. On convenience, you know that today, in most of the countries in the world, in one single visit, you can receive COVID-19 boosters and flu in the same visit. So you're not saving any visit. Now on the second part is from a clinical profile perspective, what are we looking for? And as we've shared before, and as shown by the success of our growth of influenza differentiated vaccines, clearly, people are looking at superior influenza vaccines. So that's the bar to reach in terms of both safety and efficacy. So as I mentioned today in the presentation, that's something we're going to look at. Are we able with Flumarin to reach that clinical safety and efficacy bar and then we'll move on. But there's a lot to go there. We are very confident with the flu strategy we have in place, and we are looking forward to share it with you on December 1.

[Paul Hudson, CEO & Director]

Yes. I was going to add that. And I think the December 1 meeting, you'll get to share some interesting insights, perspectives and data, which I think will help bring some clarity to the flu landscape and, in general, to the vaccine landscape. So make sure you're available for that as what I would say.

[Operator]

The next question is from Richard Vosser at JPMorgan.

[Richard Vosser, Senior Analyst]

Two please. Just on nirsevimab, obviously, strong headline data in the overall. But the hospitalizations, I think, on the primary look at that didn't meet statistical significant. So just your thoughts on whether that impacts any of the sort of reimbursement or recommendations that payers or the AICP might make? And then second question, just VAXELIS, and just thoughts on the uptake there? And what's going on with the PPH vaccines?

[Paul Hudson, CEO & Director]

Thank you, Richard. Okay. Over to you, Thomas.

[Thomas Triomphe, Executive VP & Head of Sanofi Pasteur]

Thank you, Richard. On the first part, nirsevimab. Important to clarify that the hospitalization, specifically in the MELODY trial, was not a primary end point. So the study was not powered for that. Very important to say that a prespecified pooling of hospitalization across the Phase IIb and Phase III MELODY trial was prespecified, and we've met that criteria with the ability to prevent 3 out of 4 hospitalizations. So we're not worried at all by the payer's perspective on this. So I think very good profile of nirsevimab. Again, 3 out of 4 hospitalization in a setup that pretty much is the #1 hospitalization cost today in newborns in the world. So that's for the nirsevimab element.For the second question on VAXELIS you know that we've launched VAXELIS in the U.S. in June 2021. We are still in the early stage of this. The launch is doing very well, but you probably know that when you are switching vaccines from one [indiscernible] to another. It takes time for penetrations to go through their existing vaccines and move on to the next one. Very happy with what we see in the VAXELIS launch. Of course, I remind everyone that as we've discussed last time, VAXELIS sales are not booked in the sales line. They are shared -- they are booked, sorry, at the JV Merck with Sanofi pasteur. And it's at the profit line, but you received the profit line. So overall, I will say VAXELIS, good launch, going well. Most importantly, PPL sales doing well. As we noticed before, we are in a situation where we have a decreasing birth cohort. Despite that, you see that we are doing very well on PPA sales.

[Paul Hudson, CEO & Director]

Yes. Thank you for that. I think we're really pleased with the launch, but also, at the same time, you see when you're in an established vaccine marketplace with a good standard of care, it takes time to educate and to change. And that's fine for us. We're used to doing that. It's why we're the leader. And these are thoughts to have in the back of your mind as you think about what happens in the future if other platforms, including our own, by the way, are successful mRNA in flu. What motivates in the pandemic is very different in peace times. So let's just get deeper into the conversations on December 1, which I keep trying to advertise.

[Operator]

The next question is from Keyur Parekh at Goldman Sachs. Okay. In the meantime, we can probably have Jacques Le Fur at Bryan Garnier.

[Jean-Jacques Le Fur]

Can you hear me?

[Operator]

Yes, we can.

[Jean-Jacques Le Fur]

Two questions. First for Thomas. If I understand correctly, your recombinant COVID vaccine is presented in 2 vials, 1 for the antigen and 1 for the adjuvant. Therefore, don't you think that this presentation could seriously slow down the use of your vaccine being in a pandemic or booster -- or primary vaccination or booster, sorry? And do you plan to improve this presentation, if not already done, to have, for example, ready-to-use syringe? That's my first question. And the second one is for Jean-Baptiste, your full year guidance for EPS growth appears to imply a significant slowdown for the growth -- for the EPS growth in Q4. How to interpret that? What could be the reason for this slowdown?

[Paul Hudson, CEO & Director]

Okay. Thank you so much. JB, let's start with you. What about the rest of the year? And what does that mean?

[Jean-Baptiste Chasseloup de Chatillon]

Yes. I think it's important to have in mind the very specific phasing of our BOI on EPS growth during the year quarter-on-quarter. You know that on the fourth quarter, the -- in average, looking at the past years, 8 to 9 percentage points below the average of the first quarter. So it's very normal to have this trend. Nothing will make us slow down. Of course, we want to accelerate, but we want to accelerate in science and in innovation. So that's where we are looking at and that's why we will be with the closing of TBIO, which has occurred on with the -- of course, maybe Kadmon if it's closed before year-end, you will see some more R&D costs picking up in Q4, which is expected.

[Paul Hudson, CEO & Director]

Great. Thank you. And Thomas, maybe help clarify what role we actually think will play in primary before you get into some of the mechanics?

[Thomas Triomphe, Executive VP & Head of Sanofi Pasteur]

So indeed, so COVID-19, the situation is evolving, and we are supplying and where we are needed. So we are trying to be relevant. What does that mean concretely? It means that the product we are developing is developed with our partners in Europe and North America. The express demand has clearly been about booster doses, not primary vaccination doses.And of course, back to your question, Jean-Jacques. In terms of presentation, of course, all our partners know very well, but this is a vial of antigen and a vial of adjuvants that are premixed at bedside level. So that's very clear. It didn't prevent them at all, as I mentioned previously to place orders so that we can move forward in 2022 as soon as we have our Phase III readout. But I remind everyone again that as I mentioned initially, our contribution and our engagement in COVID-19 is not about the financial, it's about having an impact on the pandemic.

[Paul Hudson, CEO & Director]

Yes. Thanks for that. And I think that -- in addition, there is an opportunity boost just to play our part, and that's our focus. But whilst we think the method of administration is really not a complication at all, it's also important to remember things that thermostable. And so I think with the pandemic, nobody is really getting into those details, but they are important details for what happens next in the roles of the established platforms and mRNA and different things like that. But if we get good data as a booster, then we'll be making what is it, Thomas, 75 million doses have been preordered?

[Thomas Triomphe, Executive VP & Head of Sanofi Pasteur]

Other European countries.

[Paul Hudson, CEO & Director]

Other European countries. So if we get there and this profile, thermostable and we're playing our part, that will just be a great thing to do. And I think it will be great for an organization to see us do it, too, right? So thank you for that.

[Operator]

Yes. We will take the final question from Peter Welford at Jefferies.

[Peter James Welford]

Firstly, just on tusamitumab, just regarding the timing of that. I think it looks as though the lung cancer readout may have gone into 2023 from '22. Can you just clarify that? Is that event-driven or due to enrollment? And similarly to Dupixent in COPD, looks like that may now be filed '24. Is that also due to one of the studies being shifted? And then the second one, just a broad one on multiple sclerosis. We, obviously, see that the B-cell therapies, the CD20 antibodies are taking a lot of market share and being widely adopted. I'm curious what your view is at this point on Sanofi's presence in multiple sclerosis? Are you looking at getting into the B-cell segment with a biologic? Do you think you need that to compete long term in multiple sclerosis? Or has Lemtrada and the experience of that sort of infrequent dose put you off having a biologic in the MS space?

[Paul Hudson, CEO & Director]

Okay. So I think I'm going to ask Bill in a moment to comment on why we think we have the winning proposition oral against CD20s and also to comment on the COPD. I think I heard you correctly, which was the move by a quarter on COPD. Nothing special in that, but we'll -- you can comment, Bill, if you like. And John, tusamitamab?

[John C. Reed]

Yes, it's really COVID-related. And the original readout was going to be tail end of '23, and so it's just slipped by a couple of months into '24. But these pipeline delays are very -- they're COVID-related.And in the COPD1, as Bill, I think, referenced, with social distancing, et cetera, patients are having fewer exacerbations. And we have criteria for a certain number of exacerbations to be eligible for the study. Otherwise, that being the primary endpoint, there's going to be very little to measure. So it's sort of a secondary consequence of the COVID as well. So those are really pandemic-related delays.

[Paul Hudson, CEO & Director]

Okay. And then Bill, MS? As you were the Godfather of Aubagio and everything else, what do you want to say?

[William J. Sibold]

Well, thanks for the question. Look, tolebrutinib is, we consider, the best-in-disease potential -- has best-in-disease potential across the whole MS disease continuum. And why is that? Well, it's brain penetrant. And it's brain penetrant at a level that actually makes a difference, we believe. You've had a lot of people try to come into the space and say they've got a BTKI that does this or does that. But we're not concerned at the moment. We believe that ours is the first. We think it's going to be the best. We have an incredibly comprehensive development program. And when we've talked about this asset, you brought up the B-cell depleters. We don't think jumping into a second or third version of Rituxan or ocrelizumab, I should say, would be the thing for us to do. And when we've been comparing tolebrutinib, we've been comparing it to the CD20s. In the sense that if you look at the impact that we have on MRI, it's consistent with those products. And if you look at the recent data that we announced at ECTRIMS, which looks at relapse rate, it's consistent. So that's the comparator. The difference is that -- we believe that's important for progressive disease to get inside the brain rather knocking on the outside in the periphery. And so we believe that this is really the product and being an oral once a day that can be the winner in the space. I'll leave it at that.

[Paul Hudson, CEO & Director]

No, that's a good place to leave it. So I think we've come to the end. Just to remind everybody as some travel is returning to normal in many places, the Vaccines Day, which I'm not sure I mentioned on December 1 will be in Paris. So I'm hopeful that those that can or feel able or motivated you should come. I can assure you it will be a very interesting and compelling day. So we look forward to that. Thanks to the team. Great progress by Sanofi through Q3. It's just the beginning, and we look forward to updating at full year. So thank you very much.