Ladies and gentlemen, thank you for standing by. Welcome to the Sanofi Q3 2021 earnings call. I would now like to turn the call over to Eva Schaefer-Jönsson , Head of Investor Relations, Sanofi. Please go ahead, Eva.
Good morning, good afternoon, and good evening to everyone. Thank you for joining us to review Sanofi's 2021 Q3 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 two , I would like to remind you that information presented in this call contains 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 risk 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 Châtillon , Chief Financial Officer. For th e Q&A, you have two options to participate. Option one, click the raise hand icon at the bottom of your screen, or option two, submit your question by clicking the Q&A icon at the bottom of the screen. With that, I'd like to turn the call over to Paul.
Well, thank you, Eva, and thanks to everyone for joining our call today. We are truly excited about the outstanding results in the Q3. 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 Q3 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 number one 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 three positive phase III readouts in prurigo nodularis, eosinophilic esophagitis, and in atopic dermatitis patients as young as six 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 10 billion sales ambition for 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, two-thirds 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. In conclusion, these results give us confidence in our growth outlook for the remainder of the year, allowing us to again raise our 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 strengthen 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 costs to succeed with commercialization are low, and hence accretion can be reached quickly. Starting on the left, our collaboration with Translate Bio was always focused on the development of next-generation vaccines and to leverage Translate Bio's expertise in messenger RNA technology.
In June of last year, well before any COVID mRNA vaccines were fully validated, we saw the opportunity to gain full access to Translate Bio'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're committed to have the first modified quadrivalent flu mRNA vaccine enter the clinic in 2022, and to deliver a pipeline of at least five 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 would 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 concerning 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.
Thanks, Paul. As indicated on the left side of slide number 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.
Five positive pivotal readouts were reported for our pipeline over the last three months, including four additional indications for Dupixent, three in dermatology, and now showing clear benefits in a gastroenterology disease. Our anti-PD-1 medicine, Libtayo, also delivered a competitive phase III performance in front-line non-small 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, in part, to effects of background medications in the placebo arm. 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 US and Japan, establishing a new standard of care for patients living with Pompe disease. On the right side of slide six, I draw your attention to some of our upcoming milestones over the next six to nine 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 syncytial 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 IMROZ trial, which investigates Sarclisa in newly diagnosed transplant-ineligible myeloma patients combined with Revlimid, Velcade, and dexamethasone, is expected to read out in the first half of 2022. Initial data for front-line myeloma patients who are eligible for transplant will be shared at a major hematology congress later this year. In hemophilia, efanesoctocog alfa, 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 nine 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 seven. If you attended our R&D day last year, you heard me describe Sanofi as an immunology company with strong core competencies in immunoscience that stretch into multiple therapeutic areas, including autoimmune inflammation, immuno-oncology, and hematology. Today, I would like to provide some insights into our work in neuroimmunology with updates on two 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-term extension program. Those data demonstrated a low annualized relapse rate over the 48-week treatment period, with 98% of patients remaining in the study.
T hese 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 two mechanisms. Number one, inhibiting B cells in the periphery and in the brain. 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 SAR443820, a brain-penetrant RIPK1 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 neuroinflammation, following his experience developing and launching our MS franchise. Bill?
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 Q3, 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 two years when compared with the Q3 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 reached the EUR 1 billion sales milestone in a single quarter 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 nine, 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-month 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 500,000 U.S. patients, further adding to the greater than 3 million patients already addressable today. Advancing to slide 10 and 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 six 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 plan 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.
Thank you, Bill. In the Q3, 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 Fluzone doses, 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 Centre 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 MELODY study, for which we already announced similar safety and tolerability compared to palivizumab at the ReSViNET Conference in November. 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 flu vaccine 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 two-thirds of the total franchise sales, when it was less than EUR 400 million just two 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're 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 modified mRNA quadrivalent 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 COVID-19 vaccine program, developed with the adjuvant of our partner, GSK. The upper part of the slide describes the ongoing phase III safety and efficacy study conducted over four continents. Now that the enrollment stage of stage one 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 two of the study, testing a bivalent formulation of five-microgram parent strain and 5-microgram beta strain has started this month. Let's now turn to the booster study at the lower part of the slide.
It will assess the immune response in adults previously immunized with a 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, thermostable 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.
Thank you, Thomas. Moving to general medicine on slide 14, we are very pleased with our performance in the Q3. 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 key cardiovascular and diabetes brands in our portfolio.
We saw demand driven strong double-digit growth of Praluent 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 Q3 of 2020. We expect sales will slightly decrease during the remainder of the year. Sales of non-core assets of the general medicine business were lower in the quarter, in line with expectations. The 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 the 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 nine months, up 14% and 16% respectively. The acquisition of Kadmon's 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 only 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 two 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 can offer 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 effective in 2022. On my slide 16, I want to highlight the progress we are making in our...
The progress we are making on our commitment to transform our General Medicines 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 to a more resilient and a more profitable General Medicines business, we have been steadily reducing the number of non-strategic 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 non-strategic 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 leverages our increasing capabilities in data, digital, and AI, positioning Sanofi as a preferred partner to HCPs. More than 60% of our HCP interactions are now supported by digital platforms, compared to only 30% in 2019. We are making solid progress with the implementation of our strategic priorities, which keeps us on track to deliver on our objective. With that, I hand over the call to Julie.
Thank you, Olivier. Following a return to growth last quarter, I'm very glad to report continuous growth in the Q3. It's a result of good performance from all geographies and almost all categories. These positive results show that the execution of our strategic roadmap 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+ brands, we have already discontinued the production or announced divestments for 111 brands, or 45% of our brands. We're also continuing our simplification endeavor 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. In Q3, the good performance of pain received an additional boost with consumer purchasing Doliprane and Advil 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. 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, and 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 gap versus market growth has been substantial. In 2020, this gap was close to five 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 four to less than half a point. With that, I hand it over to our CFO, Jean-Baptiste Châtillon.
Thank you very much. Thank you, Julie. On slide 18, turning to our financial performance, company sales increased 10.1% in the Q3, driven by excellent growth of Dupixent, differentiated flu, and 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 basis points 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, BOI clearly outgrows sales. 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 on 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 Principia, Kymab, 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 Olivier is de-complexifying the business, focusing on key markets, on employing a digitally enabled go-to-market model.
General and administration across all areas of Sanofi contributed EUR 400 million until H1 2021 through smart spending initiatives, real estate efficiencies, preferred supplier model, and digitalization. We are on track to achieve our target of EUR 2.5 billion savings by 2022, with most of this year's and next year savings to be reallocated behind our growth drivers on key programs in R&D. On slide 20, we summarize expected dynamics for Q4 of 2021. For pharma, we expect continued growth from Dupixent.
GenMed core assets are expected to grow, with Lovenox returning to stable. Divestitures 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 Translate Bio and potentially Kadmon closing.
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 -3.5 to -4.5 based on October average exchange rate. With that, I hand the call back to Paul with an important update on our ESG roadmap.
Well, thanks, JB. Today we announced our ambition to strengthen our commitment to the planet with a target to reach carbon neutrality by 2030. This marks a 20-year acceleration versus our previous targets. We are 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 have reached the first milestone with approximately 25% of all flu vaccines packaged in sustainable materials already this year.
You know, 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. 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.
We will now open the call to your questions. As a reminder, we would ask you to limit your questions to two each. For the Q&A, you have two options to participate. Option one, click the Raise Hand icon at the bottom of your screen. You will be notified when your line is open to ask your question. At that time, please make sure you unmute your microphone. Or option two, submit your question by clicking the Q&A icon at the bottom of the screen. Your question will be read by our panelists. Now we will take first question from Simon Baker at Exane. Simon?
Hi, everybody. Sorry, I was just unmuting my line. Thank you for taking my questions. I've got two, please. One on the outlook, and secondly on amcenestrant. I mean, firstly, you know, you delivered a very strong operational execution once again for the quarter. If you look at nine months, you've already exceeded your 2022 BOI margin target of 30%.
This quarter significantly exceeded your 32% 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, you know, previous comments that you've made that Dupixent is going to be margin-aggressive in 2022? I guess with that, is there anything specific you'd call out for 2022 in terms of pushing pulls that we need to take into account?
Secondly, on AMEERA-3, does the recent data from Menarini's EMERALD trial increase your level of optimism around a positive outcome, you know, given the similarities in the two trial designs? Can you just take the opportunity to remind us of the key differentiating factors of amcenestrant versus the competitive SERDs in your eyes, please? Thank you.
Simon, I'm not sure that was two questions, but we'll do our best. I think, and thank you for kicking us off. JB, so, the question of course on BOI, we're tracking ahead, what does it mean for now and onwards through 2022 in the guidance that we've already given? I think it'd be good for you to share your view.
Yeah. Simon, thank you very much for your kind words about our operational execution. 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 the way we manage as a company, which is really each time we can, while we are respecting the guidance for 2022 and 2025, we take the opportunity to add to the science, to add to our pipeline. You see what we are doing with Libtayo. 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. 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 pipelines. It's a very simple one that we have not changed since December 2019.
Yeah. Well said, JB. I mean, it's the truth. We gave you some guidance for what 2022, 2025 should look like. If we get ahead, we create a ton of value by accelerating or doubling down on our own science or adding. 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.
Yeah. Simon, thanks for the question. Indeed, the positive result for elacestrant does increase our confidence in AMEERA-3, because the field was really lacking robust data from a CDK4/6 experienced patient population. Now we have it through those data. We'll look forward to the details of the data at the San Antonio Breast Cancer Symposium.
That is encouraging for our study. Even more so, I think, because, you know, 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. Of course, the safety profile is really best in class for amcenestrant, whereas the Radius compound has a history of grade three safety events. So we're even more bullish, I think, after seeing those data.
Thanks, John. Very clear, I think, for everybody. Maybe we go to the next question.
The next question is from Peter Verdult at Citi. Pete?
Yeah, thanks. Peter Verdult, Citi. Two topics that usually don't get much air time, 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've put in place coming through?
I think you've 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 sort of...
I noted your prepared remarks, but can I just push you on VBP insulin, ballpark quantification of the likely impact? Then on Rezurock, lots of enthusiasm. Consensus for Kadmon was about $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? Thank you.
Okay, good. Good. We're really getting into it. Julie, how much of it is favorable comps, I think Pete generously said, and how much of it is just sheer excellence in execution, which bodes well for the future?
First, Pete, thank you for your question. I think our growth is really coming from three sources. Yes, there is an additional boost of COVID vaccination in pain specifically, but basically representing only for 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. 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 growth map and also a guarantee for our future success.
When you ask 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 a. Yeah, no?
Yeah.
There was another question?
The Rx to OTC switches timeline, just to shed light on the timelines.
Well, I'll pick that one up before we hand to Olivier. 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. You know, I know you pay close attention to that, but it's really cool.
Most of the 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, as we talk about Tamiflu and Xarelto, roughly around about the same time. One little nugget that I think is we haven't shared yet is that we've completed one of our self-selection studies successfully.
It's just the digital piece up front. We've got another one to go before we get talking to the regulators again. As steps go, you know, we continue to make good progress behind the scenes. Although we have a ways to go, of course, we've never said anything other than that was, you know, 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 down. Olivier, so over to you on VBP insulin.
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. Although the policy has not yet been fully disclosed and will probably be released in the course of the month 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. 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 on Rezurock, we are very excited by Kadmon. We hear very positive anecdotal feedback coming from key opinion leaders. We are expecting the closing to take place further to stakeholder approval beginning of November. We are very much looking forward to be in the field.
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 dilutive, and we are very much looking forward to enter in 2022 for Rezurock.
Yes.
Thank you.
Just not expecting it to be dilutive in-
No.
in 2022.
Thank you.
I will say, and it's worth adding, Pete, that you know, what we've done, and we've mentioned a few times up front in my comments, but you've heard me mention 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. February 5 was the other landmark for us. It was the consumer, and GenMed, and of course, Immunology piece. On consumer and GenMed, I can be equally effusive about the transformation that's underway in GenMed. I think we 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 up front of your question.
Frankly, you know, 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. I'm delighted with that. Next question.
The next one is from Wimal Kapadia at Bernstein. Vimal?
Great. Thank you very much for taking my questions. First, can I just ask about the anti-CEACAM5, please? Maybe it's a little bit of an unfair question, but typically, you know, when a target that looks at highly prevalent across multiple tumor types, you would see, you know, several players focused on the target, despite the failures we've seen, some of the same failures we've seen.
Is this Sanofi being ahead of the competition, or is it because of the strength of the molecule? Just curious to hear your thoughts there. Then just tied to that, how do you think about the potential competition from the TROP-2 target with respect to the anti-CEACAM5? 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 eights, or is duration of usage the most likely key advantage? Just on commercialization, how should we think about the launch trajectory, just given the stickiness of patients versus, you know, to previous factor eight launches? Now it's been several years, so maybe there's a little bit more appetite for switches versus the past. Just curious to hear your thoughts there as well. Thank you.
Thanks. Thanks, Vimal. I'm loving it that we're getting into the pipeline conversation. John, maybe tusamitamab, are we ahead of everybody else? And how does it compare to the other mechanisms with similar targets?
Yes. We are. You know, that class of targets, the CEA carcinoembryonic antigen is complex, but fortunately, our scientists really were able to focus on a variant, the CEACAM5, that is very tumor specific in its expression, scarcely expressed in any normal tissues. 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. We're very excited about the current molecule, and I think we've also shared that, you know, we want to do more with it and put different payloads on that molecule for different kinds of cancers. You know, 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 and together with ramucirumab CYRAMZA, including data in breast and pancreatic, as well as some data in frontline lung together with a PD-1 inhibitor. Next year will be a rich year for some readouts while we continue the phase III journey with the pivotal study. In terms of the comparison with TROP-2, we like this better than TROP-2 because according to our data, TROP-2 is not as clean in terms of expression in normal tissues versus tumor tissues compared to CEACAM5. We think our therapeutic index will be superior.
Thanks, John. Maybe, Bill, you comment on efanesoctocog or BIVV001.
Yeah. Well, why don't we just call it Efa? That makes it a lot easier for me. I can certainly tell you that. You know, we're really excited about it. You know, this is not only going to bring longer dosing interval, but a degree of higher protection. You know, 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.
Yeah, we're really excited. Now, there's been a lot of change in the market, obviously, with different mechanisms coming in which increase the switch rate. That slowed down a little bit during COVID-19. We expect, though, a lot of the market is still remains a factor market. We're excited about getting Efa out there and really seeing it becoming the leading factor.
Great. Thank you very much.
Great. Okay. Thank you. Thanks, Bill.
The next question is from Geoff Porges at Leerink. Geoff?
Geoff, we can't hear you.
Okay. In the meantime, Okay. Yes, we can hear you now.
Thanks very much. 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 rilzabrutinib. John, sorry. Could you give us a sense of what you saw in the rilzabrutinib 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 rilzabrutinib something that we should see as a future value driver and contributor or not? Could you help us understand that? And then secondly, on Dupixent, 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 three new indications. You're just getting started around the world. Yet the street really is tethered to that EUR 10 billion number, Paul. Are you willing to update it, and why isn't that EUR 15 billion or EUR 20 billion?
Okay, great. Great questions indeed. Thanks for the comment upfront about climate change. You know, there's a lot of responsibilities come with this, with the role that I have. One of the privileges of being here is that we've got a company that perhaps not well-publicized but was doing an incredible amount to the benefit of our contract with society.
We're doubling down in a few places, been very excited about that. We'll declare some other shared industry perspectives at COP26, which is not that far away. We have an absolute responsibility, as I said up front, to do something. It's not just for a poster by the elevator, it's real work being done by whole organization on a daily basis. Really proud of the organization.
Long way to go, like everybody, but really proud. John, rilzabrutinib, I think you touched on upfront, maybe there was some factors in the placebo arm with other treatments and things like that. To be candid, you know, how do you feel about how we performed and what the opportunity could be around the corner?
Thanks for the question, Geoff. You know, in that study, there was background glucocorticoids, high levels of those that patients were on in both the placebo and the treatment arm. Then, it was a complex endpoint, but part of it was, you know, how quickly can patients get to lower doses of steroids. We saw a couple things.
One was that the response rate in the placebo arm was 3-4 times higher than has been seen in any other PB study. Evidently, those high doses of glucocorticoids in the control arm really interfered with the ability to see the signal. Also, the trial which, you know, 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. There was quite a bit of heterogeneity in terms of when physicians decided to titrate down steroids, background steroids. That and some other lessons learned from the study lead us to believe that, you know, we could have had a better designed study, and at that indication, we would have approached in a different way going forward.
As I said, you know, the other data we have coming from ITP, though, on the other hand, is very encouraging. That, you know, 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 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. We are pursuing rilzabrutinib in other indications. We have high hopes that molecule, given the importance of the BTK target across a number of autoimmune allergic diseases, will, you know, will be a big player in our portfolio on a go-forward basis.
Thanks, John. Bill, you know, it's a question we're getting a lot, so be good to share your view, our view on potential peak for Dupixent.
Well, you know, 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. In the last quarter, it's been incredibly impressive as well. Just since Q2, we've had six milestones, which is just really unbelievable pace which we're going. The thing that I find really reassuring is, you know, this is a global brand, truly, with 25% of the sales now coming from outside of the U.S. You know, 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+ forecast that we gave, COPD wasn't in that.
Naturally, you may think that after we announce that in 2023 would be a time to change our guidance. You know, 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. I would say stay tuned for the moment.
Great.
Thanks very much.
Great. Thank you. Great questions. Maybe where do we go next?
The next question is from Graham Parry at Bank of America. Graham?
Great. Can you hear me okay?
Yeah.
Yes.
Brilliant. Yeah, so kind of a follow-up actually on AMEERA-3. If you can just remind us when recruitment was complete, and how long have you actually 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 Q2 call, I think you said that just looking at how events recruiting, you're looking at 4-6 months PFS. Just wondering, was that for all patients, or was 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. Perhaps you could just help us with what data in 2022 you're most looking forward to. Thanks.
Graham, I'll hand it to John, but nobody's seen any of the data, right? The difference, of course, since Q2 is that we're excited because we've seen the Menarini Radius data. So that's a good indicator, you know. 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, and 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.
Yeah. I don't know that there's a lot more to add. You know one should always be cautious about overinterpreting the fact that an event-driven study is continuing on and on. You know we'll just have to wait for the data. We're not planning to, at this point, to change the statistical analysis plan. You know we'll take a look at what we learned from the data of RADIUS when they present it at the San Antonio meeting and see if you know if there's any second thought we have around that. Right now, we're staying the course and waiting for the events. As I said, 90% of them approximately have occurred. We you know are hopeful in the next few weeks that we may get there.
I think we all just have to remain patient while we wait for the curtain to open here and to see, you know, 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, that there will be frontline data for Sarclisa next year with the most modern background backbone therapy.
That'll 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, two out of two. There's going to be more data presented at an upcoming congress at the end of this year, which will give further insights. 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. I think that's going to help further establish, you know, the level of excitement to have in that molecule based on what we see in those studies. Data will be trickling in for SAR444245, our non-alpha IL-2 throughout the year next year.
We have started in four indications at least now. You know, those data will be accruing in these signal-seeking studies across dermatology, across lung, across GI and head and neck cancer. You know, 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.
Those are, you know, a few off the top of the head. We can refer you to the backup slides that show all the readouts next year. You know, we think it's going to be a good year for us.
Thank you. Thanks John for that summary. That list is getting longer, I noticed. I just want to come back 'cause I want 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 medicine with a great balance of safety and efficacy. The recent data from Menarini Radius gives us even more confidence. You know, we'll turn the cards over as always. That's our game. We're optimistic about turning them over. Let's see where we get to. Right? Okay. Next question.
The next question is from Matt Weston at Credit Suisse. Matt?
Thank you. Two questions, please. Sticking with the pipeline. Firstly, on excuse me, fitusiran. It's had a checkered history. We've now got an 18-month delay to the readout. Is there anything that we'll see between now and 2023, 2024 that will allow investors to understand your continued optimism for the molecule? Just a quick one on the COVID universal booster strategy. Can you tell us whether now the pricing for that program, if it's positive, apologies, would be for profit or whether it would remain one where you would aim for not for profit pricing? Thank you.
Okay, Matt. Thank you. I'll toss it to Bill, fitusiran. But you know, since I joined the company, I've been. I did a lot of diligence joining the company. Then in the early days when I got in-house, I was able to see the data, and I was always excited about fitusiran because we'd 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 with, even with the delay. You know, as a management team, we look at that and go, "Can we still thread the needle on an exquisite profile?" We know that we will have to go to a lower dose probably, and we'll experience that. We also know that our interval could stretch further.
You know, and there isn't that much excitement in follow-ons from other companies. 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. You know, 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. At every turn in any data we've picked up, there are patients that have responded like they're living disease-free. We know that we just have to balance those things.
that journey so far is still worth the trade for us, and we feel that way to this point. I don't know whether John or Bill wants to add anything else.
Okay. 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 six injections per year. That's a great profile. Small subQ administration. So, you know, 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 mg dosing. So, stay tuned.
Eoin.
Yeah, that's right. You were asking what data or what we might be able to provide the investor community to help understand why we remain excited about the asset. Indeed, there'll 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 two main phase III studies. One of those was with patients with inhibitors and the other was without. Those data will be shared with the community in the next few weeks and months.
Then we go from there and further up, you know, with the studies we're doing now to explore the lower dose and the less frequent dosing intervals. The one thing I would just say, you know, because this is an siRNA drug, we have to all remember that that class of drugs has non-traditional pharmacology, right? They have
What I would call a depot-like effect and, you know, doing some titration of that is perhaps not unexpected. We know what levels we have to hit of antithrombin III reduction to hit that sweet spot, and we're just dialing into that right now.
Okay, thank you both. Thomas, boosters.
Thank you, Matt, for the question on COVID-19 boosters. Let me start quickly by saying that our strong engagement on the COVID-19 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 three different manufacturers on top of our own development.
Now, back to your initial question. As we communicated before, it's clearly going to be an affordable pricing, and we have not changed away from that at all. That's the strategy. We've already said before it'll be south of EUR 10. No change there. Now it's up to the phase III readout that's coming pretty soon.
Great. Thank you. Okay.
Thank you.
Next question.
Yeah. I'm going to take the next question from the chat, Luisa Hector from Berenberg. The first question on Dupixent is actually a three-in-one. 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?
Okay. Good. I counted four 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. China update, in-person visits, numbers, of course. Thomas, I'll come to you for a quick comment in a moment on flu and COVID.
Yeah, thanks for the question. Maybe starting in the reverse order there about pace of opening. You know, we were encouraged actually to see between last quarter and this quarter a trend up closer to 85%. 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. You know, again, we think that we see some really encouraging signs. You know, 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. Also patients with any respiratory illness, because they were so susceptible, were really kinda hunkering down at home, so you didn't see the same exacerbation rates, et cetera. I think that reached through in asthma as well as COPD as well.
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. 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.
You know, this is tracking to be one of the most successful immunology launches in China ever. 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 three 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.
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. This is a long-term story. It's off to a great start, and we'll look forward to reporting more on it in time.
Well said, Bill. Thank you. Thomas, flu, COVID, you know, approach.
The question is about the flu COVID-19 combination, interest, need versus clinical profile. For any combination, you know that we know combinations fairly well as we are the worldwide leader of pediatric combinations. We're always looking at what's the need for it, what problems are we trying to solve versus the 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. You're not saving any visit. The second part is from clinical profile perspective, what are we looking for?
As we've shared before, and as shown by the success of our growth in influenza differentiated vaccines, clearly people are looking at superior influenza vaccines. That's the bar to reach in terms of both safety and efficacy. As I mentioned today, in the presentation, that's something we're going to look at. Are we able with flu mRNA to reach that clinical safety and efficacy bar? Then we'll move on. There's a lot to go there. We are very confident with the flu strategy we have in place, and we're looking forward to share it with you on December 1st.
Yeah, I was going to add that. I think the December 1st 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. You know, make sure you're available for that is what I would say. Okay, good. Next question.
The next question is from Richard Vosser at J.P. Morgan. Richard?
Hi, thank you. Thanks for the question. 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 significance. Just your thoughts on whether that impacts any of the sort of reimbursement or recommendations that payers or the ACIP might make. Second question, just on Vaxelis and just thoughts on the uptake there and what's going on with the PPH vaccines. Thanks very much.
Thank you, Richard. Okay. Over to you, Thomas.
Thank you, Richard. On the first part on nirsevimab, important to clarify that the hospitalization specifically in the MELODY trial was not a primary endpoint, the study was not powered for that. Very important to say that a pre-specified pooling of hospitalization across the phase IIb and phase III MELODY trial was pre-specified, we've met that criteria with the ability to prevent three out of four hospitalizations. We're not worried at all by the payer's perspective on this. I think very good profile on nirsevimab. Again, three out of four hospitalization in a setup where pretty much is the number one hospitalization cause today in newborns in the world. That's from 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 pediatric immunization canal to another, it takes time for pediatricians to go through the 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 at the profit line that you receive the profit line. Overall, I would say Vaxelis, good launch, going well.
Most importantly, PPH sales doing well. As we noted before, we are in a situation where we have a decreasing birth cohort. Despite that, you see that we are doing very well on PPH sales.
Yeah. 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, you know it takes time to educate and to change. That's fine for us. We're used to doing that. That's why we're the leader. These are thoughts to have at 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 in mRNA and flu. What motivates in a pandemic is very different in peace times. Let's just get deeper into those conversations on December the first, which I keep trying to advertise. Okay. Any other questions?
The next question is from Keyur Parekh at Goldman Sachs. Keyur? Okay, in the meantime, we can probably have Jean-Jacques Le Fur at Bryan, Garnier. Jean-Jacques?
Yeah. Can you hear me? Yeah.
Yes, we can.
Two questions. First for Thomas Triomphe. If I understand correctly, your recombinant COVID-19 vaccine is presented in two vials, one for the antigen and one for the adjuvant. Therefore, don't you think that this presentation could seriously slow down the use of your vaccine in a pandemic or booster, or primary vaccination or booster, sorry? Do you plan to improve this presentation, if not already done, to have, for example, a ready-to-use syringe? That's my first question. The second one is for Jean-Baptiste de Chatillon. Your full year guidance for EPS growth appears to imply a significant slowdown for the EPS growth in Q4. How to interpret that? What could be the reason for this slowdown? Thank you.
Okay. Thank you so much. J.B., let's start with you. What about the rest of the year, and what does that mean?
Yeah. 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 Q4, the it's in average, looking at the past years, 8-9 percentage points below the average of the first three quarters. 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.
That's where we are looking at, and that's why we will be with the closing of Tidal, which has occurred, and with, of course, the Kadmon, if it's closed before year-end, you will see some more R&D costs picking up in Q4, which is expected.
Great. Thank you. Thomas, maybe help clarify what role we actually think will play out in primary before you get into some of the mechanics.
Indeed, 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.
Of course, back to your question, Jean-Jacques, in terms of presentation, of course, all our partners know very well that this is a vial of an 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 on 2022 as soon as we have our phase III readout.
I remind everyone again that as I mentioned initially, our contribution and our engagement in COVID-19 is not about the financials. It's about having an impact on the pandemic.
Yeah, thanks for that. I think that in addition, you know, there is a real opportunity in booster just to play our part, and that's our focus. While we think the method of administration is really, you know, not a complication at all, it's also important to remember things like we're thermostable. You know, I think with the pandemic, nobody's really getting into those details, but they're important details for what happens next in the roles of the established platforms and mRNA and different things like that. If we get good data as a booster, then, you know, we'll be making, what is it, Thomas, 75 million doses have been pre-ordered.
By European countries, absolutely.
By the European countries. You know, 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'll be great for our own organization to see us do it too, right? So thank you for that. Maybe it's the last question.
Yes. We'll take the final question from Peter Welford at Jefferies. Peter?
Hi. Yes, thanks for taking my question. Firstly, just on tusamitamab, just regarding the timing of that. I think it looks as though the lung cancer readout may have gone into 2023 from 2022. Can you just clarify, is that event driven or due to enrollment? And similarly to Dupixent in COPD, looks like that may now be filed 2024. Is that also due to one of the studies being shifted? And then the second one, just a broad one on multiple sclerosis. We're obviously seeing that the B cell therapies, the CD20 antibodies are taking a lot of market share and been 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'd 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? Thank you.
I think I'm going to ask Bill in a moment to comment on why we think we have the winning proposition or 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. You can comment, Bill, if you like. John, tusamitamab?
Yeah. It's really COVID related and the original readout was going to be tail end of 2023, and so it's just slipped by a couple months into 2024. These pipeline delays are very. They're COVID related. In you know, in the COPD one, as Bill, I think, referenced, with social distancing, et cetera, patients are having fewer exacerbations and you know, we have criteria for a certain number of exacerbations to be eligible for the study.
Otherwise, you know, that being the primary endpoint, there's going to be very little to measure. You know, it's sort of a secondary consequence of the COVID as well. Those are really pandemic related delays.
Okay. Bill, MS. As you know, with the godfather of Aubagio and everything else, what do you want to say?
Well, thanks for the question. Look, tolebrutinib is, we consider the best in disease potential across the whole MS disease continuum. Why is that? Well, you know, 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. You know, 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. 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. If you look at the recent data that we announced at ECTRIMS, which looks at relapse rate, it's consistent.
That's the comparator. The difference is that different. We believe that's important for progressive disease to get inside the brain rather than knocking on the outside in the periphery. You know, 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.
No, that's a good place to leave it. 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 the first, will be in Paris. I'm hopeful that those that can or feel able or motivated, you should come. I can assure you, it'll be a very interesting, compelling day. Yeah, 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 a full year. Thank you very much.