Good afternoon and good evening to everyone. Thank you for joining us to review Sanofi's 2022 second 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 3, 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 4. Our speakers on the call today are Paul Hudson, Chief Executive Officer, the Global Business Unit heads, Bill Sibold, Thomas Triomphe, Olivier Charmeil, and Julie Van Ongevalle, and Jean-Baptiste de Chatillon, Chief Financial Officer.
For the 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. I'm truly delighted to share our outstanding financial results with you today. As always with me here in the room are the key members of the executive team to take you through our business and financial performance. We delivered sales growth of 8.1%, continuing the strong performance we saw in Q1. Our growth in Specialty Care has accelerated to more than 21%. Dupixent posted nearly EUR 2 billion in sales and is still growing at a stellar rate above 40%. Our rare disease franchise has grown double-digit, driven by legacy products and recent approvals. Continued growth in PPH, further recovery in travel and booster vaccines drove another strong quarter for our vaccines business. In General Medicines, the focus put on our core assets, well, it continues to pay off.
Consumer Healthcare delivered another quarter of above-market sales growth, and this speaks volumes about the speed at which our business is transforming into a truly agile, fast-moving, and consumer-centric organization. Moving to Slide 7, let's take a moment to consider the immense potential of Dupixent. Five years into launch, this medicine continues to grow at a remarkable pace. While we have already treated over 450,000 patients worldwide, we know it's only really starting at this point. The markets where we are approved are still largely under-penetrated, with an eligible population of around 7 million patients. This quarter alone, we added 150,000 eligible patients, thanks to approvals in areas of higher unmet need, such as pediatric asthma in Europe and eosinophilic esophagitis in the U.S.
Let me mention here the approval we received in the United States for the youngest children suffering from atopic dermatitis, making Dupixent the first and only biologic medicine approved in all age groups from infancy to adulthood. That's a complete paradigm shift. The breadth and depth of the Dupixent label is setting aside this mega brand from all other medicines in this area. On Slide 8 , as we get close to the end of the first phase of our six-year strategic plan, let's take a moment to highlight some of our achievements and future perspectives. We have delivered eight consecutive quarters of sales growth. More recently, growth even accelerated to high single digits. While it's probably at least a decade since such a performance was achieved, but above all, it is a proof point that our focus on winning assets combined with strong commercial execution is clearly paying off.
At the same time, our profitability improved, and thanks to the efficiencies and savings made across the company, we are making these improvements sustainable by largely reinvesting in our growth drivers and our science. As a result, we remain on track to reach our 30% BOI margin guidance this year, as we had committed back in 2019. We are on a quest to modernize the company. This modernization includes a deep cultural transformation, but also important structural changes. The recent and successful spin-out of EuroAPI is a major milestone, and so is the implementation of our CHC standalone model. Looking ahead, several key factors will be instrumental for our strategic execution. Clearly, Dupixent remains the number one driver of our growth story.
It will help to manage the LOE of Aubagio in the U.S. in 2023, our last meaningful LOE in this decade, making Sanofi the pharma stock with the least exposed to generic competition among our peer group. We will continue to focus on R&D productivity through increased investment in breakthrough science and first and best-in-class assets. Our pipeline is maturing fast, and we will have multiple chances for transformative launches in the upcoming years. In the short term, we're focused on making Nirsevimab a success, a success story by achieving all infant protection from RSV starting next year. Following shortly after, we strongly believe efanesoctocog alfa will have the potential to revolutionize treatment for hemophilia A patients. Our belief in tolebrutinib, our oral brain-penetrant BTK inhibitor to address the full spectrum of multiple sclerosis, remains unwavering.
Based on compelling phase IIb efficacy data, we launched the largest phase III clinical program in MS, and more than 2,000 patients are currently on tolebrutinib therapy with duration of treatment up to three years. We expect the first pivotal readout by the end of next year. It's disappointing that the FDA asked us to pause new patient enrollment in the U.S. without assessing the impact of our trial protocol revisions implemented back in May. Let me point out that all of the 150 patients enrolled into the phase III program between implementation of the revised protocols in May and the partial clinical hold in the U.S. at the end of June, none have had any sign of drug-induced liver injury. We received written feedback from the FDA and are confident to address the FDA's request for additional information by the end of this quarter.
Meanwhile, the studies continue in dozens of countries around the world. Moving to Slide 9, let's take a closer look at our R&D transformation marked by clear prioritization and long-term ambition to lead with innovation. This slide illustrates just a few examples of the significant shift in R&D productivity we've made over the past three years, such as accelerating the development of Dupixent across a wide range of type 2 inflammatory diseases and building an industry-leading immunology pipeline. I simply could not be prouder of the organization and the progress we have made over the past couple of years. Moving to Slide 10 and our hemophilia pipeline. If you had the chance to follow ISTH, where the pivotal data for efanesoctocog alfa was presented earlier this month, you will almost certainly agree efanesoctocog alfa is reaching levels of efficacy that have simply never been seen before.
There is little reason, in my view, for patients that are using factor today to be on anything other than efanesoctocog alfa in the future, and Bill will take a little more, talk a little more about this and the upcoming launch in a few minutes. Another fact became apparent to me when I had the chance to engage with key opinion leaders at ISTH. Beyond factor, innovative hemophilia treatments have to be truly once monthly or even less frequently. Let's not forget the potential for fitusiran. We look forward to presenting more data from the ongoing fitusiran program next year based on its revised schedule of every other month. Moving on to Slide 11 and nirsevimab. Our team is working around the clock to make this first in class immunization solution available to protect all infants against RSV once approved.
RSV was recently on the agenda of the general meeting of the U.S. Advisory Committee on Immunization Practices, ACIP, and recognized as the most common cause of hospitalization in U.S. infants. With excellent results of the pivotal trials, nirsevimab is positioned to play an essential role in achieving the greatly needed all infant protection against RSV. Advancing to Slide 12. You remember that we accepted the challenge to run a COVID-19 efficacy study at a time when many people had already been infected or were starting to get vaccinated during the first campaigns. Yes, we're not the first, but we knew the recombinant protein platform was not built for speed. However, it allowed us to include a vaccine based on a variant into the phase III study and to test for efficacy in an Omicron world.
The results were published recently for our beta-containing vaccine, clearly underlining the strength of our science and our recombinant platform. Why beta? Well, because it allows for a broad cross-protection across a number of variants of concern. As we said many times, this is not a financial play for us. The profile of our recombinant booster vaccine makes it an interesting solution for payers, given the efficacy and the safety. Once authorized, our recombinant booster could play a meaningful role. Let me close on Slide 13 with the recent progress of our CSR strategy. We launched the Sanofi Global Health in April 2021 during the pandemic, and it is clearly picking up pace now. The model of Sanofi Global Health is simply unique.
It is the first and only global initiative to provide the access to a broad portfolio of medicines in so many countries and across so many areas using its own brand. We presented our ESG ambitions at a dedicated investor event earlier this month, and Sanofi Global Health was recognized as the flagship initiative by attendees, by those at our event, as well as by the leading ESG rating agencies. To sum up, as you can see, our scientific and commercial agenda is moving at speed, and so is our commitment to society. I'm very proud of all the progress made, and with that, I hand over to Bill for his update on Specialty Care. Bill?
Well, thank you, Paul. Moving to Specialty Care, I'm excited to discuss the stellar performance in Q2, where all franchises, as you can see, are growing. Sales exceeded EUR 4 billion, making Specialty Care Sanofi's biggest GBU in the quarter, growing at almost 22%. This quarter, the core driver of performance was once again Dupixent, with its outstanding sales across geographies in approved indications and the recent addition of EoE in the U.S. Rare disease emerged with double-digit growth in the quarter, driven primarily by continued patient accruals in addition to favorable phasing, which are typical for this business overall throughout the year. However, we do not change our long-standing trajectory of mid-single-digit growth for this attractive franchise.
In oncology, our launch momentum continues for Sarclisa as we look forward to the additional potential growth opportunity in first line based on the IMROZ pivotal data readout later this year. Moving to Slide 16, let's take a closer look at Dupixent performance in Q2, where we see a meaningful step-up in sales from Q1 2022, depicted on the graph on the left. With the growth rate almost 40% compared to Q2 2021, we see the published sales figure benefiting from continued increase in underlying demand and the stronger US dollar. These effects together have added EUR 720 million in incremental sales versus Q2 2021.
As Paul highlighted already, in Q2 alone, we added 150,000 eligible patients and expanded into GI with the approval of eosinophilic esophagitis, where Dupixent is the first and only medicine indicated to treat the disease. Additionally, progress has been made to address the need in the pediatric population, where the well-established safety profile of Dupixent is an important differentiator. Turning to Slide 17, you can see we now have five positive pivotal trial readouts in the pediatric population, substantially increasing the number of eligible patients for Dupixent. This achievement is based on a robust and ever-growing safety database across type 2 inflammatory diseases, where Sanofi and Regeneron continue to generate a compelling body of safety and efficacy evidence compared to new market entrants. We believe this further elevates Dupixent's profile to be the preferred treatment choice with physicians, payers, and patients.
Shifting focus to another leading franchise, rare blood disorders, we presented two late breakers at our priority assets, Efa and fitusiran, at the ISTH conference earlier this month. While closely engaging with the members of the hemophilia community, and specifically the physician experts in the field, we highlighted the strong scientific evidence for our innovative hemophilia treatments with their potential to raise the bar for both efficacy and treatment burden. We have highlighted the key data for Efa on this slide. Looking first at the primary and key secondary endpoints, the primary endpoint was met as the median ABR was zero, with an interquartile range of zero to 1.04. Using a model-based mean, the ABR was 0.71. These impressive data do not come as a surprise to investigators, but rather fulfilling the expectation to be a highly efficacious treatment.
The key secondary endpoint depicted on the right compared the intrapatient ABR between prior factor VIII prophylaxis and Efa prophylaxis. The mean ABR for the prior factor VIII prophylaxis in the patients that participated in the pre-study was 2.96. With Efa prophylaxis, however, the mean ABR was 0.69, an impressive 77% decrease in the mean more than half of the number of infusions that they were doing on their prior prophylaxis. Ultimately, Efa offers a significant decrease in patient treatment burden with strong levels of protection and lower mean ABR. Based on the data, we see Efa as creating a new class. We believe this is a high-efficacy class offering superior efficacy above any product that there has been in hemophilia A and anything that we see in development.
Near normal factor levels for the majority of the week and true once-weekly dosing. This new standard of possibility I would call it, is just starting to be appreciated and opens up efanesoctocog alfa to the EUR 5 billion factor therapy segment, which represents 70% of the overall hemophilia A non-inhibitor market valued at EUR 7.4 billion. With that, I hand over to Thomas to update you on the vaccines business.
Thank you, Bill. In Q2, we continued our strong trajectory of Q1 and delivered 8.7% sales growth. As the COVID pandemic progresses, we see a recovery of the booster vaccines and travel franchises across all regions. Our PPH franchise also demonstrated good performance. We experienced a limited impact from China regional lockdowns, so growth in the rest of the world and Europe more than compensated for the expected decline in reported US PPH sales. That is due to the solid uptake of Vaxelis. As explained before, we do not report sales of Vaxelis. We book the share of profit in other operating income. The quarterly performance of meningitis and influenza franchises, including some phasing elements in Q2. On the next slide, I'd like to mention a significant milestone that took place in June.
The US Advisory Committee on Immunization Practices, ACIP, made a very important recommendation to enhance protection of their senior citizens against influenza and its severe consequences. The committee reviewed large sets of data available for every influenza vaccines licensed in the US, and they recognized that a standard dose of flu vaccine was not optimal to protect seniors above 65 years of age. That recommendation for the elderly population was updated. It includes now Fluzone High-Dose and Flublok, and the abundance of data showing the benefit of Fluzone High-Dose was especially highlighted. This important step from an influential immunization recommendation body is key to raise the bar for influenza immunization in people above the age of 65, and I am glad that more seniors in the future will benefit from protection beyond flu against the severe consequences of influenza, such as pneumonia and cardiovascular events.
Now, as we are approaching the Northern Hemisphere 2022 influenza seasons, some uncertainties regarding possible COVID-19-related disruptions of health systems do remain. However, I also want to reiterate that we expect another year of record flu sales, thanks to our strategy to focus on high-value vaccines that provide improved protection. With that, I hand the call over to Olivier.
Thank you, Thomas. Moving now to General Medicines on Slide 21. The execution of our strategy continued to deliver, with Genzyme growing 6% in Q2, where we continue to gain market share. Total Gen Med sales decreased 4.1% to EUR 6.6 billion, also due to the impact of that divestiture and the deconsolidation of EuroAPI third-party sales. Adjusting for these, Gen Med sales decreased 1%.
Sales on non-core assets were down 8.6% in the quarter, and mainly reflected expected VBP-related impact on Lantus and our legacy oncology portfolio in China. In the U.S., Lantus sales are affected by the overall erosion of the basal insulin market. Second, product divestitures, which are key to our ongoing strategic streamlining efforts. Excluding the impact of divestiture, non-core assets were down 6.7%. On Slide 22, I'd like to focus now on the performance of our core assets in the second quarter. Similar to Q1, Lovenox sales decreased 10.9% in Q2, reflecting less COVID-19 related demand and also an increase in biosimilar competition. Toujeo sales were up 2.4% with growth in Europe and the U.S., partially offset by the expected impact of the implementation of the VBP for insulin from May in China.
Total glargine sales, which include Toujeo and Lantus, were down 24% in China in Q2. At 2021 full-year results, we expected that total glargine sales in China would decrease around 30% in 2022. I'm pleased to announce that as of today, we expect 30% not to be exceeded. In April, at ADA Congress, we presented positive results of InRange, a head-to-head study comparing Toujeo and Degludec in type 1 diabetes using time in range as a primary endpoint. These results will help us to close the gap in type 1 diabetes versus Degludec, and could strengthen Toujeo's position in type 2 diabetes. We are particularly pleased with our transplant franchise, which delivered a strong performance. Sales are driven by Rezurock as well as by the strong performance of Thymoglobulin.
Rezurock has achieved a robust adoption with more than 1,000 patients treated since launch, corresponding to around 25% of the current addressable market and demonstrating excellent persistency rates. Sarclisa sales grew 148% in Q2, driven by continued growth in Europe as well as a ramp-up in China, where Sarclisa is included in the NRDL since the beginning of the year. Sales growth also profited from a growth net worth in the US related to earlier periods. Excluding this effect, sales of Sarclisa grew close to 50%. Plavix delivered strong growth in China, with sales up 19.1%. This consistent strong performance in China confirms the success of our participation in the VBP program and the recent successful renewal.
Global Plavix sales were flat in second quarter due to the lower sales in Europe and a mandatory price cut in Japan beginning of April. Advancing to Slide 23, we continue our efforts to provide access to insulin to those most in need, and not only in developing countries, but also in mature markets. Since the start of this month, uninsured people living with diabetes in the United States can obtain insulin such as Lantus, Toujeo, Admelog at $35 for a 30-day supply through our Value Program. This is a significant step forward from our previous value offer of $99 for a month supply. In 2021, the Value Program was used more than 97,000 times, providing many people with diabetes in the U.S. the medications they need. With that, I hand the call over to Julie.
Thank you, Olivier. In Consumer Healthcare, we continue to execute on our three strategic priorities to deliver consistent growth. As you can see on this page, on a twelve-month basis, we are growing above market for the third quarter in a row. It is rewarding to see that our team's hard work is delivering results, while striding along towards our standalone structure, greatly contributing to our agility to capture market opportunities and respond to competition. While also keeping simplifying our portfolio. We're now down to 140 brands from over 250 18 months ago. While we have to compensate for some top-line losses in the short term, the greater focus and the increased resource and budget allocations behind our priorities are clearly paying off.
Regarding the Cialis Rx-to-OTC switch, as you know, the FDA placed our actual use trial on clinical hold in May. Since then, I'm glad to report we had a very constructive meeting with the agency, and importantly, we received clarity from them on the path forward. We are very encouraged by that interaction and will continue our conversations with the FDA in the coming months with a goal to finalize our next steps. Trust our motivation to progress this project remains unchanged, because Cialis switch can provide improved access to safe and effective medicine for this underserved condition. From a business opportunity, the size of that opportunity remains unchanged. On the next slide, moving now to Q2 performance, I'm very glad to report that despite a strong Q2 last year, we delivered over 9% sales growth.
The like-for-like organic growth, meaning excluding the impact of the product divestments in the same period, is a double-digit growth of 10.5%. Pricing contributed to 3.5 percentage points of this growth. With the COVID-19 pandemic, the Omicron variant often causing symptoms that are very similar to strong cold symptoms, this quarter was marked by a cough and cold season that lasted longer than usual. We were able to respond quickly and get our key brands in store. As a result, we grew almost 75%. Also, the digestive wellness, our biggest category, we maintain strong momentum, reaching, again, almost double-digit growth. I'm very proud to observe the strength of our business with growth coming from all categories and all geographies. With that, I hand it over to our CFO, Jean-Baptiste.
Thank you. Thank you, Julie. As highlighted by my colleagues, we continue to deliver strong top line results derived from our key growth drivers across our businesses. Going now to business EPS, I'm pleased to report a 16.7% growth at constant exchange rate. Let's look at the drivers of this great performance, even slightly accelerated when comparing to the 16.1% growth reported in Q1. As guided, the gross margin continues to improve versus last year, now reaching 74.1%, thanks to favorable portfolio shift to Specialty Care products and efficiencies. SG&A is growing considerably less than sales, and a lower effective tax rate of 19% creates additional support. I would like to highlight that R&D keeps growing at a significant pace due to our expanding pipeline on platform acquisitions such as Translate Bio, Kymab, Kiadis, Amunix, Synthorx.
Other operating income consists mainly of the Regional Alliance balance this quarter. Moving to Slide 28, on taking a year-to-date view, sales grew 8.4% versus H1 2021 and our BOI margin improves by 110 basis points, putting us on a clear trajectory to deliver on our 30% margin target in 2022. We increased our R&D investment by more than 13% the first half of EUR 3.1 billion funding the development of our priority assets on our latest bolt-on acquisitions. A quick update on our savings program on Slide 31. We have reached the EUR 2.5 billion in the last six months, especially driven by operational excellence in the area of cost of sales, as shown by the nice improvement in gross margin during the year.
This still includes around EUR 200 million of pandemic-related savings that we said will come back over time, so our ambition remains to achieve the underlying EUR 2.5 billion by year-end. You might wonder, what did we do with this EUR 2.5 billion savings? Well, turning to Slide 30, what I would like to highlight again is that all of the OpEx-related savings were reinvested. In fact, total cumulative OpEx grew by EUR 500 million due to investments in R&D and selling costs. Most of the savings still to be generated in the second half are going to be allocated to key programs in R&D. Let's now move to the outlook on Slide 32. With a very positive margin development in the first half, we still have a bit to go to the 30% target.
The top part of the graph, we are highlighting the drivers. The main contributor will be the Dupixent growth, accretive to group BOI margin starting from this year, as pointed out before. Other contributing factors will be capital gains from planned divestitures, which we estimate to be around EUR 350 million in the second half, meaning that the expected total amount of EUR 600 million for the full year remains unchanged. Restructuring of the alliance around the deal that closed earlier this month will also have a positive effect, especially due to the accelerated reimbursement of the development balance associated with Regeneron on Sanofi's antibody collaboration. As announced early June, Regeneron will increase from 10% to 20% the share of its profits that is paid to Sanofi to reimburse Sanofi-funded development expenses.
This will apply also retrospectively to Q2 and will start to be booked in Q3. On the other hand, there are also some negative drivers to keep in mind. We have guided for 2022 growth margin improvement to be weighted to the first half of 2022. In the second half, underlying improvements are expected to be offset by macroeconomic headwinds such as increased cost of energy, transportation, as well as labor cost. The VBP on insulin in China will also negatively affect the growth margin for that part of the business. Regarding H2 sales expectations, Specialty Care and CHC will continue on their respective growth trajectories with more moderate rates. Gen Med growth will be more pronounced towards the end of the year, and we continue to expect another record year of flu sales with a split 60/40 between Q3 and Q4 due to our excellent time to market.
Getting to the last slide on the full-year 2022 guidance. We are upgrading our expectations on EPS growth to around 15% at constant exchange rate on full-year positive currency impact of 7.5-8.5% based on July actual rates. To wrap it up, eight quarters of growth, another quarter with double-digit EPS growth, sound execution along the plan we laid out. Important achievements were made during the quarter. EuroAPI shares were listed in May, and the stock is performing nicely. Three more approvals received for Dupixent, covering all age groups in AD now in the US. Efanesoctocog alfa was submitted in the US, the second priority asset to be filed following nirsevimab in the EU in February. With the transformation progressing, we remain on track to achieve our 30% UI target on double-digit EPS growth in 2022.
Let's open the call now for Q&A.
Thanks, JB. As a reminder, we would like to ask you to limit your questions to no more than two. For the Q&A, you have two options to participate. Option one, click the Raise Hand icon, and I see many of you have already done this. You will be notified when your line is open to ask a question, and at that time, please make sure you unmute your microphone. Option two is submit your question by clicking the Q&A icon at the bottom of the screen, and your question will then be read out by us. We will now take the first question.
Yes, the first question will be from Wimal Kapadia from Bernstein. Wimal?
Great. Thank you very much for taking my question. Wimal Kapadia from Bernstein. First, can I just ask on margins, please? Jean-Baptiste, you talked about the renegotiation of resulting in a faster payback for Dupixent development. This seems like quite a smart move because the 10% of profits is quite meaningful on our metrics of a few hundred million EUR next year. My question really is, what impact is this going to have on margins in 2H 2023 and then the 2025 target? How should we really think about this change in the context of the greater than 32% target in 2025? Is it fair to assume now, you know, you'll be comfortably ahead of this target because of this, and you could really potentially expand margins next year as well through the Dupixent, dupilumab? That's my first question.
My second question is just on tolebrutinib. You know, it seems like you've recruited the majority of patients required. My question really is, do you need to actually add more patients on the study, or do you have enough to file regardless of the clinical hold being lifted? Just in terms of commercial implications as a result, you know, it's quite a competitive market. Has this safety signal really changed your thoughts on the commercial potential? Thank you.
Is it one question we ask people, Wimal? All right. All right, Wimal. Thank you so much, as always, for kicking us off. Thank you also for the compliment on the construction of the deal with Regeneron. I think it worked out very well for both parties. JB, where do you stand? Is it in the numbers? I think people want to know.
Yeah. Thank you, Vimal. Effectively, we're glad to have done this simplification of our work with our partner. You know, this amount of R&D we invested initially was due to be paid on very long period of time. This acceleration is quite meaningful and will effectively impact positively our P&L in 2023, 2024, 2025. It's really very nice. You also know that we'll get the royalties out of the global sales, which will come on top of that. The question is that going to expand our margin or change our target? No, Vimal.
As I said several times, every opportunity we see to increase or improve our P&L or increase our margin, we are reinvesting in R&D. That's where we are 'cause that's what we want to do. We are here for that. That's really go for innovation and invest in our long-term growth by really being true to this commitment of investing in science.
Thank you. Well said. John Reed, tolebrutinib, will we have enough patients to file?
Yes. We're quite far along with the relapsing remitting studies, GEMINI 1 and 2, and the secondary progressive. The primary progressive, we're still enrolling there. You know, we've got more than 2,000 patients currently on study, and we continue to enroll around the globe with the exception of the United States and a couple other countries. We feel like we'll still have the recruitments completed by the end of this year. We haven't changed our timelines at this point. You know, just to contextualize these, you know, we were cruising along quite well, and we're about 2,000 patients into the studies.
In April, we experienced what appeared to be a couple cases of possible drug-induced liver injury, and that prompted us to make changes to the protocol in May that removed underlying risk factors for injury because these patients all, for the majority of them, had what looked like underlying conditions that could have been contributors. We also increased the frequency of monitoring to every two weeks as opposed to every month. We're quite confident that that would then reduce the risk that these sorts of events might be seen again in the future. We are proceeding accordingly. We've enrolled close to 200 patients so far. They're all doing well.
The patients that we had on study, you know, who had been now on therapy for months are doing fine. We're quite confident we'll get through this. We've got a checklist from the FDA of things that they are asking for in terms of information, and we're checking off that checklist and hope to have that back to them by the end of September and then move forward.
Good. Thanks, John. Very clear. Bill, profile, where we stand?
Yeah. Look, we see this still being the best-in-disease product. For the reasons that we've said from the beginning, it's a brain-penetrant BTKi, which we think is really important. We know that from the long-term study, the extension, that we have still about, you know, 88% of patients that remain on therapy, 85% of patients relapse-free at 72 weeks, and an 85% reduction in Gd-enhancing lesions. That's still a profile which is great, and we expect it to be a multi-billion euro blockbuster.
Well said, Bill. Okay. Next question.
Yes. The next question will be from Jo Walton from Credit Suisse. Jo?
Thank you. My question, I have one on Dupixent and one, just general one on U.S. healthcare reform and anything that you'd like to tell us about, you know, your perception of what seems to be likely to happen in the U.S. My question on Dupixent is whether you can give us any help on sales by indication. You talk a lot about the atopic dermatitis penetration, but you don't tell us so much about the asthma penetration. So just so that we can see as we go forward, where you could get particular growth.
If I could just add to that, is there any region or indication where you're getting to a level that governments are now thinking, "Well, this is such a large drug, I could do with a price cut." Is there any concern that you're now getting to that sort of level with higher price erosion likely? Thank you.
Thanks, Jo. Good to see you, at least from a distance, at ISTH. I was hoping for an efanesoctocog question. Okay. Dupixent, Bill, why don't you take that as sales by indication and, you know, and the penetration in asthma and other indications.
Yeah. Thanks, Jo. You know, we won't break it out by indication. As we've said all along, AD, it's been the first. It's the market that's the indication that's the least mature based upon us being the first product there. And there's still plenty of growth, and we're still at about that 9% penetration rate in the U.S. We still see that as being, you know, the biggest indication. Now, as you looked at asthma, it's about 19% biologics penetration. As we said in the past, we think that can go up to about 30% or 40%. We've reported on previous calls from a respiratory perspective, we are the leading asset in respiratory, bar none.
I think, you know, just to provide the perspective, you know, we hear this quarter every now and then a question about a competitor getting an indication. I think you have to look at what we presented in the call here and what Paul talked about. You know, just with what we have approved this quarter, it's an additional 150,000 patient opportunity. That is just a sampling of the additional age groups we're going into and additional indications. There is plenty of room for this to continue to grow. Now, growth clearly gets attention, but this is a product with demonstrated efficacy that we haven't found anyone in the world who's pushed back on the benefit of what this product has to offer.
You know, with additional competition, et cetera, with additional indications, there will always be additional pricing discussions. We've planned from the beginning for this to be a multi-indication, multi-country product. We feel that we've handled it extremely well, and we don't expect anything above any kind of pricing erosion that would be typical in the space.
Yeah. Thanks, Bill. I mean, the health economic data that supports Dupixent beyond, on every indication is absolutely incredible. You know, the unmet need is massive. Okay, Jo, the other question I think was around the U.S. and reconciliation. Maybe just take a step back for a second. You know, we've come a long way from H.R. 3 to the current reconciliation package that's on the table. Remind you, it's not done yet, right? You probably are even more aware of some of the technical processes that we have to go through in the U.S. or at least this type of bill has to go through. We've not even got to the Byrd Bath there yet for those that understand how the technical opportunity there.
Either which way, it's not good for patients, it's not good for affordability for patients, not good for innovation in general. Let's be clear about that. I think we all know that. I had the opportunity to sit down with close to nine senators in one-on-ones last week to get our heads around it. I'm putting my energy into it like most of my peers are, and everybody is trying to help remind people that it's not where it needs to be. It is not doing what it's supposed to do in terms of helping patients through innovation, affordability, I mentioned. As for us as a company, you know, of course, we have a little less exposure in the United States in general than many of our peers.
Because our portfolio is a little diverse, you see different levels of technical exposure. I think in general, you know, we would say that it's one of those things that we just have to take. Of course, we wouldn't have much choice. We'll find out what it says next week. Not good for patients, not good for innovation, frankly. You know, we'll find a way as always. Thanks, Jo.
The next question will be from Graham Parry from BofA. Graham?
Great. Thanks for taking my questions. Firstly, on efanesoctocog alfa, I think, Paul, you said, and the physicians on your call said no reason for a factor patient not to switch. The only reason perhaps that there could be is if they can't get reimbursement for it. Could you just help us understand your pricing and access strategy that you're thinking about for efanesoctocog alfa as you head towards launch? On tolebrutinib, I think, John, you just said a couple of cases of drug-induced liver injury. It sounds like a very low incidence. Is it fair to assume the incidence here that you're seeing in the trial is below the evobrutinib phase II trials, where around 26% of patients saw raised liver enzymes and 11% discontinued due to liver enzyme elevations.
In short, do you still see tolebrutinib as potentially differentiated on liver profile versus evobrutinib? Thank you.
Okay. Graham, thank you. We'll come to John in a moment. As for efanesoctocog alfa, we look forward to sharing the brand name with you when it's approved. You know, it's an interesting one, right? We haven't got to sharing price yet, but you jump in if you want to comment. The efficacy is so good. My own time at ISTH really reinforced that. The important thing to remember is what worked against us with Hemlibra versus Eloctate works for us with efanesoctocog alfa, because patients, if they wanna move in this market, they will move. They'll get switched, they'll get initiated. The momentum is patients wanting as normal life as possible. You know, we are very excited about what we'll do with this medicine.
Bill, did you want to add anything?
No, I think that's right. I think, you know, a couple things that are favorable as well is what we've seen globally is still a recognition for innovation. Clearly when you look in the hemophilia space, you know, don't see anything in the real immediate term that looks to be as innovative as Efa. Now, if the market becomes a purely efficacy-driven market, there's really only one choice, because there's really only one product that has ever gotten you close to near normal for the majority of the week. We have high expectations. We're excited about it. We believe that there will be a path to reimbursing for it, and we believe that patients will want to and they will seek out a higher efficacy option.
Thank you, Bill Sibold. John Reed, how about liver enzymes?
Yeah, Graham, you're correct. The frequency which we've seen these possible cases of drug-induced liver injury has been very few patients, a fraction of a percent, whereas with evobrutinib, they've had double digit, you know, numbers of percentages of patients that have had to go off study because of liver transaminase increases. We still believe that we have the strongest safety profile. The other thing is that these cases always occur within the first couple months of treatment, so the monitoring is important to do potentially in the beginning of the therapy. After patients have been on therapy for a couple months, if they haven't had one of these issues, they're gonna be fine, it looks like.
As I said, we have 2,000-plus patients still on study and up to this point, all well. We think we've got a good plan for, you know, for going forward with reducing the problem and we'll work through getting this resolved with the FDA as expeditiously as possible.
Yeah, maybe.
Sorry, John, the line just cut there. Did you say a few % versus double-digit for ivabradine? Sorry, just wanted to clarify that.
No, I said a fraction of 1%, is what he's saying.
Okay, thank you.
We're talking about Evos. Yeah.
Double digits for Evo. You know, we take a few questions on it. Honestly, I mean, let's be really clear. I think we made the right change to the protocol. We feel very good about that. We're supplying the information to the regulator, and it's really basically just the U.S., and then we're heading to get this corrected with the plan to come off hold in Q4. That's what we're working towards. Okay, next question.
Yes. Next question will be from Richard Vosser from J.P. Morgan.
Richard.
Hi. Yeah, thanks for taking my questions. Perhaps switching topics to vaccines first of all, and the flu supply. Maybe you could give us some context on the amount of Fluzone High-Dose we should anticipate in Europe and US this season. Do you have enough capacity for, say, 60 million doses this year? And then a couple of questions or one question, sorry, on consumer. Perhaps you could give us some context on how you see the market growth for branded products going forward in Q3 and Q4, and are you thinking people will downtrade as we see the economic crisis maybe worsening a bit? And if I can be cheeky, Tamiflu wasn't mentioned with Cialis, so just what's going on with Tamiflu? Thanks very much.
Okay, good. Thank you. Maybe I'll come to you, Julie, in a moment, but Thomas Triomphe, Fluzone High-Dose and volumes.
Overall, we're in very good spot from a flu supply perspective. Clearly, supply is not gonna be any problem, as it's not been a problem for the past two years. You know very well that we built capacity a few years ago to feel very confident, and it comes at a time, as I mentioned during the presentation, of the ACIP recommendation. That's why we feel strong about delivering a record flu year, this year, which comes on top of significant growth over the past few years, as you know very well. It's not small feat. I expect therefore a good Fluzone High-Dose delivery both in Europe and in the US.
We're in shape, and of course that is, that can be seen, this good level of supply, by the indication of the fact that when you look at the timing, we expect roughly, even though it's a bit early to be definitive, about 60% of the flu second half of the year to be in Q3 versus 40% of it being in Q4, which reflect the quality of the supply we're getting.
Thanks, Thomas. It's great work actually by the vaccine team. I'm excited to get ready for the season. Julie, will people go from branded to generics with the pressure on people's out-of-pocket expenses? Maybe a quick comment on Tamiflu.
Sure.
Thank you, Richard, for the question. First of all, what we've seen in healthcare is that shares of private labels have been relatively stable in the past two years. However, with increased inflation pressure and economic downturn, we are very conscious that consumers will have to make choices more than in the past. Again, we've seen that in our area, consumers and patients make the least compromises. Again, health is definitely most important. Efficacy and very strong is a very strong loyalty driver even more so in healthcare. As a result, the quality and the value of our brands is what really makes a difference, and that's what we're bringing forward, and here I'm very confident. On Tamiflu.
On Tamiflu, nothing has changed from the last quarter in that we are waiting for the flu season to be able to start the new testing. No news on Tamiflu so far.
Yeah. Thank you. Thank you, Julie. Ask them to be same branded in the pharmacy.
Of course.
Okay, next question.
The next question will be from David Risinger from SVB Leerink.
Yes. Thanks very much. Can you hear me?
Yeah.
Great. Congrats on the performance. I have questions on tolebrutinib and amcenestrant. With regard to tolebrutinib, have you already enrolled enough U.S. patients in order to be able to deliver a sufficient U.S. regulatory filing? And what is your current estimation for timing for top-line phase III results from your global RMS studies? Regarding amcenestrant, is there an opportunity to pursue a more targeted approach with ESR1-mutant patients with greater likelihood of generating compelling efficacy results? Thank you very much.
Okay. David, thank you. I think we've touched already a little bit on the tolebrutinib question on enrollments and submissions. John, do you have anything extra to add?
Just that the RMS studies we expect will read out the end of next year. Then the progressive studies would be the following year, which is pretty much on par with what we had originally forecasted. At this point, you know, it is a global trial. It is actually the series of trials, and this is the largest campaign that's ever been orchestrated for an MS drug. It is global. We do feel like we have the U.S. sufficiently covered. I forget what was the other.
Yeah. Amcenestrant. Do you think we need to look at an ESR1 mutation to show a clear efficacy, or should we just focus on the adjuvant setting where the opportunity is?
Well, actually you'll be able to see the ESR1 mutant versus wild type data at ESMO in terms of what we show in the late line setting. But in terms of where we really have always felt the sweet spot for this mechanism in the adjuvant space, you know, we're quite comfortable with the profile there where there's very small percentage of mutations in that setting, and most patients still have wild type receptor. We're active against both wild type and mutant receptors, so we sort of have our bases covered, I would say.
Okay. Thanks, John. Next question, please.
Yes. The next question will be from Mark Purcell from Morgan Stanley.
Mark.
Great. Thank you. Thank you very much for taking my questions. I have two. The first one on R&D investment. How should we think about the level of investment in R&D going forward over the medium term? How should we think about investment discipline here? I mean, Sanofi's now got so many new platforms to choose from, delivering new medicines through the development engine. A nice problem to have. At 15% of sales in terms of an R&D margin is a nice offset potentially with gross margin. It'd be interesting to understand your level of ambition there in terms of increasing investment in future innovation. Then the second question was on CEACAM5 ADC.
Can you help us understand your ambitions beyond lung cancer, as the understanding of ADCs, I guess, is changing quite a bit at the moment, and what the key data points are to watch out for over the next 12 months in lung cancer?
Okay. Thanks, Mark. John, I think back to you. Actually, before that, maybe, you'd like to make a comment, JB, on R&D investment levels.
Yeah. Thanks for the question. There's no magic number on. Maybe by the way, we should not consider consumer health within the equation because it doesn't consume this R&D budget. Our vision is clear. It's to increase within, so in respect of our guidance, is to increase as much as we can our spend on R&D. That's what we're doing. I know that sometimes it's, I see the consensus that some are not believing us when we said we would add another half a billion EUR this year in our P&L. That's what we are doing, and you see it in Q2. It's actually a proof point of our decisiveness in terms of being true to this commitment.
Yeah, I think. I repeat, no magic number, but the direction is clear.
Thank you. Thanks, JB. John, CEACAM5 ADC beyond lung?
Yes. We are pursuing that molecule for other CEACAM5 positive tumors, gastric, breast, et cetera. Still collecting data in those contexts. Of course in lung, we're also in phase II studies in front line in combo with pembrolizumab and exploring, you know, whether we can move into the front line setting with that. I thought the question was more broad about modalities in general. If that's the case, then indeed we have quite substantially expanded and modernized our drug discovery infrastructure with new modalities. Some of that organic, a lot of it through bolt-on acquisitions. Our ability to support those from a CMC manufacturing, I feel quite confident we've been able to leverage, you know, our capabilities, for example, in microbial production of insulin to support the Synthorx platform, synthetic biology, which is the E.
Coli platform, to support the Amunix platform, to support the nanobody platform, where again we use microbial species. All that's really been able to just kind of modify what we had available at our Frankfurt site there. The other biologics platforms have, we've been able to adapt what we've had there. We're really leveraging a lot of capabilities in Vaccines for some of the others. For example, the AAV platform. You know, making viruses, live attenuated viruses for vaccines is something our colleagues there have known how to do for years, and we're actually doing our GMP production in a Vaccines facility there and leveraging that. Of course, the commitment to the mRNA platform that the Vaccines colleagues made, you just...
We just plugged right into that for the therapeutics as well.
Yeah. Thanks, John. Let me try and connect those dots together actually, because it's a really interesting question. To JB's point, you know, our priority is to deliver our financial guidance and commitments, and we work really hard to reallocate to R&D within that. Let's just be really clear, because that's the goal within what we've committed. Outside of that, the platform piece, you know, we made a decision with John and the team to take a platform base. One of the reasons why we have 13 shots on goal in immunology, half, more than half are antibodies. We get a really efficient entry to have a shot, at least to proof of concept and beyond. I think we knew that was probably gonna be our best way.
The real magic behind the platforms is when we start to converge the platforms, and that's why as we bring Amunix in, say on top of antibodies, you know, it starts to help us get to that tunable piece. There is individual platform opportunity and volume at scale as we get into our stride. I think we're not far off. There's the convergence of the platforms that bring a lot of opportunity, and we work really hard as a team, the people around this table and beyond, to make sure that we can redistribute, deliver guidance and redistribute to R&D. That's the job, and that's the fun of the job too.
Okay. Next question.
The next question will be from Keyur Parekh from Goldman Sachs.
Hi, thank you for taking my questions. John, if I could just confirm your answer to David's earlier question. Are you confident that you have enough U.S. patients, given the extra patients you are recruiting on the tolebrutinib program kind of elsewhere around the world, for it to be okay from an FDA perspective? Secondly, kind of, just looking at the Consumer Healthcare business, clearly kind of demonstrating very strong execution and continued growth, but your guidance assumes kind of much more deceleration in growth towards the second half of the year. Just wondering beyond tougher comps, is there anything else you are seeing from an in-market perspective that is driving, or should we think of it as classic Sanofi conservatism on this guidance over here? Thank you.
Okay. I didn't quite get the second question, but while you somebody's gonna repeat it to me. On the first question, John, I'm not sure there's much more to add on the tolebrutinib piece. I can understand everybody's level of interest. Let's just fast recap, right? We'd adjusted the protocol. We were in good shape. We get the questions, we get the partial hold. We know what we need to do to come off it. We have to get that done. We come off it in Q4, and we get on with it. You know, if there's anything more to add to that at any point, we'll share.
Well, just, you know, the word partial I think is very important, because it means all the patients who had already been enrolled and were 60 days plus past still are on study, including in the United States. All those patients continue to be followed until, you know, the outcome of the study. I think let's remember that. Also we didn't re-emphasize here, but it probably merits that the liver injury cases we saw were reversible. You know, nobody went to transplant. Nobody died. I mean, they were picked up by routine monitoring. Yeah, we feel like, yeah, we can address this. We've got to just, you know, give the FDA their checklist of things that they want as additional return visits.
Thanks, John. JB, are you being conservative?
Okay. You're having a go at me. No. I don't have more insight than you have. I don't see anything else that you can see, so it's very transparent. The information we gave for the second half of the year, yeah, we're raising our guidance. Let's summarize it. That's how conservative we are.
Okay. Next question, please.
This is-
I think there was a question on consumer.
Oh, sure. Yeah, please.
On how we see the remainder of the year, I think what's important. First of all, thank you for saying what you said, because yes, not so long ago we were losing share for a while, and it's really since Q4 last year that we've been catching up on a twelve-month rolling basis. Looking ahead, after this fifth I think strong quarter, we expect the market to experience a more normalized growth because we have to keep in mind that we had a high the market overall, and we did too, a higher 2021 comparison. We still have the ambition to continue to grow in line or slightly ahead of the market. I hope that answers your question.
Yeah. Thank you. Well said. Okay. Where are we?
Yes. Next question, Tim Anderson from Wolfe.
Thank you. Couple of questions. On Dupixent, and it's really on China. In China, there's at least one lookalike product moving into phase III, and in certain categories we've seen fast follower products kind of cause headaches for multinationals. I'm wondering how much China is in your EUR 13 billion forecast for Dupixent, and just in general, how are you viewing local market competitors that you see potentially emerging near term? Second question on tolebrutinib, just back on LFT elevations. I know the frequency was low. Were any of those grade 3 or grade 4? Have any other countries besides the U.S. put the drug on clinical hold?
Okay. Well, that I'm gonna throw to you, Bill, Dupi in China. I think, you know, at this point we've answered all the tolebrutinib questions. I understand as we get more information, we'll share it with you as we get into Q3, but getting off the hold's the priority, and we'll update you. Bill, anything to add on China as part of the weight point of EUR 13 billion and/or the fast follow-up to market?
It is. It certainly is, Paul, and I think what we've also said is that we expect it to be a blockbuster in its own right in China. The opportunity there, we think is still very significant. We're just at the beginning. Just like we are everywhere else in the world, we're at the beginning in China. We've seen some really great uptake, additional indications that we've been as successful with, and positive data reads at readouts as early with some other asthma trial there. Yes, you know, we think that within China, any follower is gonna have to, first of all, compete against the product which has kinda opened up the AD market in China.
We expect that we have, you know, high hopes that there will be a recognition of the IP that exists within China, and we think that the expertise that we've brought to the market will be recognized and, you know, as we get more information on it. We're not even certain if anything will come at this point, but we know we've, as I said, it's baked into our EUR 1 billion-plus forecast that we have and the midpoint of EUR 13 billion that Paul said.
Yeah. Maybe I think we've started really well.
Oh, great start.
in China. I mean, really well.
Unprecedented start really for a biologic.
I think that we should share, you know, Tumbalin launches in China. We'll get a moment.
Yeah.
It's a rocket ship. Even after the lockdown, we haven't had a chance to comment about it today, but patients coming literally straight back out and getting to see their dermatologist.
That's right.
Bodes well. Bodes really well. Okay. Next question, please.
Yes. The next question will be from Laura Sutcliffe from UBS.
Hi, Laura.
Hi. Thank you for taking my questions. I have a question on rilzabrutinib, please. Could you just talk to the commercial potential for that in ITP, given that we've seen a molecule terminated in this space elsewhere today, albeit not an oral, even though there was no negative data. Secondly, could you maybe just tell us why you've discontinued dupilumab in peanut allergy? Thanks.
Okay. Well, John, I'll come to you on peanut allergy.
Okay.
Bill, maybe just a general comment about rilzabrutinib oral, the approach, and then maybe ITP, if you would like to answer that, and then we'll come to
Yeah
John.
No, thanks for the question. Look, let me start with ITP. There's about 25,000 chronic ITP adults in the U.S. They're eligible for the second line plus treatments after steroids. You know, again, coming fresh off of ISTH and hearing from the physicians, there was a lot of enthusiasm about Rilza in the ITP space. They clearly see there's an unmet need there, and they like the fast onset of action and durable effect that took place. You know, we'll continue to wait for the data, so to speak. You know, we see that as a nice potential. Also, you know, with Rilza we've got a broad development plan in it.
We're also looking at it in AD, looking at it in asthma, looking at it in IgG4, wAIHA, et cetera. This is one of those products that we think is so fundamental to biology that it gets us into a lot of spaces. Obviously, you've seen the BTKi and the effect in MS with tolebrutinib, but we think rilzabrutinib allows us to go to other places as well. Quite promising in an ITP specifically, strong data, fast onset of action, durable effect.
Okay. Thanks. Thanks, Bill. John, any comment on peanut allergy?
Well, I'd have to tell you that, you know, it's really difficult to do good clinical trials in that space. We did do some phase II kind of exploratory work. Just decided it, you know, was not ranking as high on our strategic priorities as other places we could invest. We kinda just let it stay there for now.
Okay. Thank you. Okay, next question, please.
Next question is from Richard Parkes from Exane.
Oh, hi. Yeah, sorry. It's Simon, actually. Apologies for that. Two questions and none on tolebrutinib. Thank you. Firstly, a follow-up on the margin question, if you could. I mean, you're able to consistently overdeliver with the strong results, you know, despite your commitment to meaningfully increase your investment in R&D. I'm thinking just taking into account your prior commentary around meaningful mix and gross margin step-up from 2024, you know, the Regeneron renegotiation you've just talked about earlier, and your focus on high-margin offerings. I mean, the question really is when do you think you may be able to quantify the more than 32% operating targets for 2025? Just a quick follow on, can you quantify the remaining R&D spend that has to be repaid by Regeneron?
The second question is just I was wondering if you could be willing to share your latest views on the Zantac litigation liabilities with the first trial confirmed for early next year. I mean, I appreciate Brent Wisner has become somewhat of a defense attorney celebrity post-litigation. I'm just wondering if you could potentially share your thoughts on your exposure in light of his remarks that Zantac could potentially dwarf Roundup. Thank you.
Okay. Simon, thank you. Let's start with JB, then I'll go to Julie.
Yes. Sorry, Simon, I'll have to repeat the same message. We do all to increase our R&D spend as much as we can if we have room to do it because you see our portfolio, it's a need for innovation, and we want to stand by this commitment. Yeah, on the total impact, well, as an indication, I can tell you that we will not have finished having this accelerated repayment where it will impact us at least till 2026. Yes, it's a very significant amount of R&D that we will see coming back to us through this acceleration of the development balance. That's great. That means that we can invest in more innovation.
Thank you. Julie, do you wanna make some comments on Zantac?
Sure. First I wanna remind that Sanofi voluntarily withdrew the OTC Zantac from the market in 2019 and Zantac OTC products containing ranitidine remain off the market. Both the FDA and Sanofi have conducted investigations into the levels of NDMA in ranitidine products. The FDA has stated that although NDMA may cause harm in large amounts, the NDMA levels that the FDA found in Zantac ranitidine from preliminary tests barely exceeds the amounts found in common foods. Therefore, we at Sanofi believe strongly in our defenses. Sanofi contends that the plaintiffs will be unable to prove that Zantac causes any type of cancer. Basically, the science does simply not support the plaintiffs' claims. We're confident.
Okay. Urooj, do you wanna add anything?
I think Julie covered it well.
Thank you.
There's no reliable evidence whatsoever that Zantac causes cancer. The amounts are stuff that's found in drinking water, common foods, and we feel very strongly about our defenses. We acted responsibly, more than responsibly at all times.
Okay. Thank you. Next question.
Next question will be from Simon Baker from Redburn.
Thank you very much for taking my question. Two, if I may. One on vaccines and one on consumer. Also just a quick clarification on Fluzone record year, Thomas. Is that record year in terms of just value or volume and value? The main question on vaccines was you indicated that you have data for the COVID booster against Omicron BA.1. I just wondered at this still fairly early stage if you have any data against BA.4 and BA.5. Then on consumer, Julie, I wonder if you could give us a little color on the regional split of pricing. You said it was 3.5% overall. If you could give us any color on that, would be very handy.
Also, some of the moving parts within what was a very impressive performance on the gross margins. Well, I'm assuming there were pulls and pushes on that. If you could give us some color, that would be very helpful. Thank you.
Okay. Thanks, Simon. Thomas, then regarding flu season, split between value, volume of course, and you heard it as well as I did, and BA.4, BA.5 with COVID.
Yeah. Thanks for the question, Simon. It's been a while since we stopped talking about volume, so what we're really looking is how do we contemplate value? Each time we are talking about record flu year, it's about sales. And especially as we you know very well we've pivoted from standard dose flu vaccines a few years ago to deliver differentiated flu vaccines that provide protection beyond flu endpoint itself. We really and the market is totally recognizing the value of those products, and therefore each time we're talking about a record year, it's in value in sales. Your second question is about COVID-19. Very early data is showing against BA.4, BA.5 early read, but shows exactly what we have seen against BA.1, BA.2.
I'm confident that the booster we will be providing to the market, if approved, has the ability to be a booster of use and of choice as discussed before by Paul during his presentation. We believe it's a good opportunity for public health decision makers.
Thank you, Thomas. Julie, I'm not sure how we normally break price down publicly. If you choose not to share it's okay. By region.
I don't think we usually share it. What I can say is that the majority of our portfolio we can impact pricing, and that we obviously do it based on the actual raw material costs, the competitive behavior by region, as well as the consumer necessity.
Yeah.
All regions have increased prices.
Thank you. JB, gross margin?
Yeah. Well, margin of sort of CHC, in terms of gross margin first, it's part of the business that we can reprice with our headwinds, it's maintaining quite well. We see that across the board on the regions. In terms of overall stability of BOI margin, of course, you cannot read through our current sectoral publication, the effective level of margin of CHC. That will be externalized more something like next year. Okay, thank you. Next question, please.
Yes, the next question will be from Seamus Fernandez, sorry, from Guggenheim.
Yeah, thanks. Hoping you guys could update us on amlitelimab and the progress towards you know hopefully entering registrational trials. Maybe you can just talk a little bit about the differentiation that you see of that product as well. I know it's core to you know the continued attempts towards dominance in the immunology space. Love to hear your thoughts along those lines, and when we might see data. I believe the first quarter of next year was the target, but didn't know if we might see advancement into a pivotal sooner than that. Thanks.
Okay. Thanks, Seamus. John, why do we have the winner with OX40?
Yeah, let me maybe do the differentiation first and then cover where we are with aspiration to accelerate. On the differentiation. As you know, we're targeting the ligand, whereas others are targeting the receptor. There, you know, reason to believe that could be better from the standpoint that the ligand is prevalent at lower levels, and you have less problem really covering the full target and getting good target exposure, we believe. More importantly probably is that, amlitelimab is a non-depleting antibody. It doesn't kill the cells that express the ligand, whereas the competitor molecule that binds the receptor actually kills the cells.
We think over the long run, because it's a depleting antibody, that's going to be disadvantageous because among the cells that express that OX40 receptor are regulatory T cells, the immunosuppressive cells that you need for immune homeostasis. We also think because that is a depleting antibody that activates complement, another mechanism, that that's probably why the competing molecule has shown evidence of infusion types of reactions with febrile episodes and other sorts of evidence of inflammatory responses in the first couple injections. Of course, we don't have anything like that with amlitelimab. In terms of the acceleration, we are very much working directly with all the health authorities around the world to explore what is possible.
We're still trying to work out the best path forward for meeting all the regulatory requirements, not only around demonstrating the efficacy, but also the safety database that will be required, et cetera. We wanna make sure that the study population does represent you know the diversity of patients that struggle with atopic dermatitis, both in terms of what therapies they've experienced as well as, of course, the DE&I types of issues around representation. We're really working with the health authorities to figure out how quickly can we deliver high-quality data. We will have more to tell you as those discussions and plans unfold.
Okay. I think, Thanks, John. I think just mechanistically, we have the advantage. I think we wanna get there as soon as we can. You know, we're ambitious. We told you that. We're looking for all the opportunities to do that. When we can confirm that, we will do that. But it's gonna be really important to make sure everybody understands the full benefit of what this medicine can do, and had the opportunity to lead with the team, the amlitelimab team last week, and it's starting to get really exciting. I really appreciate the question, Seamus. Do you have time for one more?
One more. The last one will be from Peter Verdult from Citi.
Peter.
Yeah. Thanks. Thanks, Paul. Thanks, everyone. Peter Verdult, Citi. Two questions. Just for Paul first. Coming up to three years since the Play to Win strategy was laid out, you obviously continue to be very keen to highlight the absence of LOEs post-Aubagio. So the question is, when might we get revised midterm targets, and are they likely to pivot towards top-line growth aspirations rather than staying focused on BOI and margins and free cash flow? Then second, very quickly for John on the pipeline, IRAK4, is this asset still viable in light of the recent data we saw highlighting a QTc signal? Thank you.
Excellent questions. Some reflections maybe at three years, I think it's incredible the speed of transformation in this company and the people in this company, incredible and doing incredible things. I would probably say we're ahead of where I'd hoped, you know, in the weeks leading up to joining. You know, I think we have to earn the right to move to that sort of top-line story. We have to deliver the science. We have to deliver the guidance and, you know, we said back in 2019 we would earn the credibility from delivering exactly what we said we would do. We don't. That's non-negotiable for us, and I think we're building quite a high degree of trust on that.
Maybe there'll come a moment where we get to look further ahead, as of course you'd expect that, and to be bold about what that looks like for us because of course, you know, investments in R&D. You know, that's an important consideration over the long term. I do think we have to earn it. We're not quite at that point yet, and when we're ready to share that with you, we will do. As for IRAK4, you know, it's really fascinating. We touched a little bit on rilzabrutinib earlier. You know, in biologic-dominated marketplaces, there is room for beautifully put together orals. You know, it's been the holy grail for most companies and most diseases. It's a needle to thread.
You know, you have to remember that the goal is not always to be as good as a biologic, there to be a relevant medicine on the journey perhaps to a biologic. We know what you have to look like to be a successful oral, and the volumes you use slightly earlier in diseases. It's not unlike some of the oral and oral in psoriasis. You have to think in those terms. We remain enthusiastic about the IRAK4 mechanisms. You know, we're working with the teams on making sure that because we're careful and judicious around where we spend our R&D dollars, that we think we would have a profile that could be meaningful share-wise in the market. Stay with us on that.
I'm glad you asked about it, because as we build out our immunology leadership across the entire industry, we've got some really interesting shots on goal, different mechanisms, different patient populations, and different methods of delivery. Yeah, thanks, Peter, for that. That's a good way to maybe bring it to an end, if that's okay. You know, thanks to the team, thanks to everything people doing at Sanofi. Thanks to everybody that is tuned in. We're doing exactly what we would say we would do and a little bit more, and we look forward to reconnecting with you in Q3 and in between. Thank you very much.