Sanofi (SNY) Q2 2022 Earnings Call Transcript

Sanofi (SNY 5.90%)
Q2 2022 Earnings Call
Jul 28, 2022, 8:30 a.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Eva Schaefer-Jansen

Good morning, 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. And for that, I'd like to turn the call over to Paul.

Paul Hudson -- Chief Executive Officer

Well, thank you, Eva, and thanks to everyone for joining. I'm truly delighted to show our outstanding financial results with you today. And 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 up. 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. And while we have already treated over 450,000 patients worldwide, we know it's certainly really starting at this point. The markets where we are approved are still largely underpenetrated, with an eligible population of around 7 million patients. This quarter alone, we added 150,000 eligible patients, thanks to approvals in areas of high unmet need, such as pediatric asthma in Europe and in eosinophilic esophagitis in the U.S.

And then we mentioned 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, as 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.

And 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 spinout of EUROAPI is a major milestone, and so is the implementation of our CHC stand-alone model.

Looking ahead, several key factors will be instrumental for our strategic execution. Clearly, Dupixent remains the No. a1 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'll continue to focus on our 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 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 unwavered. Based on compelling Phase 2b efficacy data, we launched the largest Phase 3 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 3 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 a 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 certainly 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 have the chance to follow ISTH, with the pivotal data for efanesoctocog alfa that was presented this month, you will almost certainly agree that efanesoctocog alfa is reaching levels of efficacy that have simply never been seen before.

There was little reason, in my view, for patients that are using factor VIII 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. And another fact became apparent to me when I had the chance to engage with key opinion leaders at ISTH. Beyond the fact, innovative hemophilia treatments have to be truly once monthly or even less frequently.

So let's not forget the potential for fitusiran. We look forward to presenting more data from the upcoming -- sorry, 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.

And now on 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 starting to get vaccinated during the first campaigns. Yes, we're not the first, but we knew the recombinant protein platform was not built to speed. However, it allowed us to include a vaccine based on a variant into the Phase 3 study and to test for efficacy in an Omicron world. Results were published recently for our beta-containing vaccine, clearly underlying 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 to payers, given the efficacy and the safety. Whilst authorized, our recombinant booster could play a meaningful role.

So 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 early this month, and Sanofi Global Health was recognized as a flagship initiative by attendees, by those that were at the 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?

Bill Sibold -- Executive Vice President, Sanofi Genzyme

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 MRAS 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 U.S. 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 data phase 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 on 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 burdens. 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 0, with an interquartile range of 0 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 intra-patient 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 is 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 efa to the EUR 5 billion factor therapy segment, which represents 70% of the overall hemophilia A noninhibitor market valued at EUR 7.4 billion. With that, I hand over to Thomas to update you on the vaccines business.

Thomas Triomphe -- Executive Vice President, Sanofi Pasteur

Thank you, Bill. In Q2, we continued on 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 BPH 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 U.S. 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 and 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 U.S. Advisory Committee on Immunization Practices, ACIP, made a very important recommendation to enhance protection of their senior citizens against influenza and severe consequences.

The committee reviewed last sets of data available for every influenza vaccines licensed in the U.S. And they recognize that the 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 the 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're 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.

Olivier Charmeil -- Executive Vice President, General Medicines

Thank you, Thomas. Moving now to general medicine on Slide 21. The execution of our strategy continues to deliver, with core assets growing 6% in Q2, where we continue to gain market share. Total gen med sales decreased 4.1% to EUR 3.6 billion, also due to the impact of the divestiture and the deconsolidation of EUROAPI third-party sales.

Adjusting for these, gen med sales decreased 1%. Sales on noncore assets were down 8.6% in the quarter and mainly reflected expected -- the 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, noncore 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. Our 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 ATTD Congress, we presented positive results of InRange, the 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.

Praluent sales grew 148% in Q2, driven by continued growth in Europe, as well as the ramp-up in China, where Praluent is included in the NRDL since the beginning of the year. Sales growth also profited from a gross-to-net true-up in the U.S. related to earlier periods. Excluding this effect, sales of Praluent grew close to 50%.

Plavix delivered strong growth in China, with sales up 19.1%. This consistent strong performance in China confirmed 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 the 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 USD 35 for a 30-day supply through our Valyou program. This is a significant step forward from our previous value offer of USD 99 for a month's supply. In 2021, the Valyou 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.

Julie Van Ongevalle -- Executive Vice President, Consumer Healthcare

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 12-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 toward our stand-alone structure, greatly contributing to our agility to capture market opportunities and respond to competition, and 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 topline 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 we'll 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. And 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 the 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 variants 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. And as a result, we grew almost 75%.

Also, the Digestive Wellness, our biggest category, we maintained 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.

Jean-Baptiste Chasseloup de Chatillon -- Chief Financial Officer & Executive Vice President

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. Turning 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 and platform acquisitions, such as TBIO, Kadmon, Kiadis, and lately, Amunix.

Other operating income consists mainly of the Regeneron alliance balance this quarter. Moving to Slide 28 and taking a year-to-date view. Sales grew 8.4% versus H1 2021, and our BOI improved by 110 bps, putting us on a clear trajectory to deliver on our 30% margin target in '22. We increased our R&D investment by more than 13% in the first half of EUR 3.1 billion from the development of our priority assets and 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 that will come back over time. So our ambition remains to achieve the underlying EUR 2.5 billion by year end.

And 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, the total cumulative opex grew by EUR 500 million due to investments in R&D and selling costs. Most of these 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. On 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. The restructuring of the alliance around Libtayo that closed earlier this month will also have a positive effect, especially due to the accelerated reimbursement of the development balance associated with Regeneron and Sanofi's antibody collaboration. As announced early June, Regeneron will increase from 10% to 20% the share of its profit 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 gross margin improvement to be weighted to the first half of '22. 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 costs. The VBP and insulins in China will also negatively affect the gross 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 toward the end of the year, and we continue to expect another record year of sales with a split 60-40 between Q3 and Q4 due to our excellent time to market. So 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 and foresee a positive currency impact of 7.5% to 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 U.S.; efanesoctocog alfa was submitted in the U.S., 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% BOI target and double-digit EPS growth in 2022. Let's open the call now for Q&A.

Eva Schaefer-Jansen

Thanks, J-B. [Operator instructions] And so for the Q&A, you have two options to participate. Option 1, click the raise hand icon, and I've seen many of you have already done this. You will be notified when your line is open to ask your 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 are going to be read out by us. So we will now take the first question.

Questions & Answers:

Operator

The first question will be from Wimal Kapadia from Bernstein. Wimal?

Wimal Kapadia -- AllianceBernstein -- Analyst

Great. Thank you very much for taking my question. So first, can I just ask on margins, please? So Jean-Baptiste, you talked about the renegotiation of resulting in a faster payback for Dupi development. I mean, this seems like quite a smart move because the 10% of profit is quite meaningful.

On our math, it's a few hundred million euro next year. So my question really is what impact this is 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 '25? Is it fair to assume now you'll be comfortably ahead of this target because of this, and you can really potentially expand margins next year as well through the Toujeo patent cliff? So that's my first question. My second question is just on tolebrutinib. It seems like you've recruited the majority of patients required.

So 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? And then just in terms of commercial implications as a result, it's quite a competitive market. So has the safety signal really changed your thoughts on the commercial potential? Thank you.

Paul Hudson -- Chief Executive Officer

Is it one question we ask people to ask? 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. J-B.

So where do you stand? Is it in the numbers? I think people want to know.

Jean-Baptiste Chasseloup de Chatillon -- Chief Financial Officer & Executive Vice President

Yeah. Thank you, Wimal. Effectively, we're glad to have the simplification of our work with our partner. This amount of R&D we invested initially was due to be paid on a very long period of time, and this acceleration is quite meaningful and will effectively impact positively our P&L in '23, '24, '25, and it's really nice.

You also know that we will get the royalties out of the sales -- the global sales, which will come on top of that. So the question is, is that going to expand our margin or change our target? No, Wimal. 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.

That's what we want to do. That's -- we are here for that, as we go for innovation and invest in our long-term growth by really being true to this commitment of investing in science.

Paul Hudson -- Chief Executive Officer

Thank you. Well said. John Reed, tolebrutinib, will we have enough patients to file?

John Reed -- Executive Vice President, Global Head of Research and Development

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. 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 of other countries.

So we feel like we'll still have the recruitments completed by the end of this year, so we haven't changed our time lines at this point. Just to contextualize these, we're -- we were cruising along quite well, and we're about 2,000 patients into the studies. And then in April, we experienced what appeared to be a couple of cases of hospital drug-induced liver injury. And that prompted us to make changes to the protocol in May that removed the underlying risk factors for injury because these patients all -- for the most -- the majority of them had what looked like underlying conditions that could have been contributors.

And we also increased the frequency of monitoring to every two weeks as opposed to every month. And we're quite confident that that would then reduce the risk that these sorts of events might be seen again in the future and are proceeding accordingly. We've enrolled it close to 200 patients so far. They're all doing well.

And the patients that we had on study for -- who had been now on therapy for quite some months are doing fine. So we're quite confident we'll get through this. We've got a checklist from the FDA of things that they were asking for in terms of information. And we're checking off that checklist and help -- have that back to them by the end of September and then move forward.

Paul Hudson -- Chief Executive Officer

Thanks, John, very clear. Bill, profile, where we stand?

Bill Sibold -- Executive Vice President, Sanofi Genzyme

Yeah. Look, we see this still being the best-in-disease product, and 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 had [inaudible], 88% of patients that remain on therapy, 85% of patients relapse-free at 72 weeks, and then 85% reduction in Gd-enhancing lesions.

That's still a profile which is great, and we expect it to be a multibillion-euro blockbuster.

Paul Hudson -- Chief Executive Officer

Well said, Bill. OK. Next question.

Operator

The next question will be from Jo Walton from Credit Suisse. Jo?

Jo Walton -- Credit Suisse -- Analyst

Thank you. My question, I have one on Dupi and one -- just a general one on U.S. healthcare reform, and anything that you'd like to tell us about your perception of what seems to be likely to happen in the U.S. But my question on Dupi 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. And if I could just add to that. Was 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 can do with the prior drug? So is there any concern that you're now getting to that sort of level with higher price erosion likely? Thank you.

Paul Hudson -- Chief Executive Officer

Thanks, Jo. Good to see you, at least, from a distance at ISTH. I was hoping for an efanesoctocog question. But OK, Dupi.

Bill, why don't you take that, sales by indication and the penetration of in -- as for another indication?

Bill Sibold -- Executive Vice President, Sanofi Genzyme

Yes. Thanks, Jo. 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. So we still see that as being the biggest indication. Now as you look 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%. And we've reported on previous calls, from a respiratory perspective, we are the leading asset in respiratory, bar none. And I think just to provide the perspective, we hear this quarter, every now and then, a question about a competitor getting an indication. And I think you have to look at what we presented in the call here and what Paul talked about, just with what we have approved this quarter, it's an additional 150,000 patient opportunity.

And that is just a sampling of the additional age groups we're going into, an additional indication. So 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. So with additional competition, etc., with additional indications, there will always be additional pricing discussions, but we've planned from the beginning for this to be a multi-indication, multi-country product.

So 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. So --

Paul Hudson -- Chief Executive Officer

Yes. Thanks, Bill. I mean, the health economic data that supports Dupi and beyond on every indication is absolutely incredible. So the unmet need is massive.

So OK, Jo, the other question I think was around the U.S. and reconciliation. So maybe just take a step back for a second. So we've come a long way from HR3 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 had to through. We've not even got to the birdbath 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. And 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.

So I'm putting my energy into it than the rest 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 and affordability, I mentioned. As for us, as a company, of course, we have a little less exposure in the United States in general than many of our peers.

And then if you -- because our portfolio is a little diverse, you see different levels of technical exposure. And I think, in general, we would say that we -- that it's one of those things that we just have to take. Of course, we don't have much choice. We'll find out what it says next week.

Not good for patients, not good for innovation, frankly, but we'll find a way, as always. So thanks, Jo.

Operator

The next question will be from Graham Parry from BofA. Graham?

Graham Parry -- Bank of America Merrill Lynch -- Analyst

Hey, thanks for taking my questions. So firstly on efanesoctocog. 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.

So could you just help us understand your pricing and access strategy that you're thinking about for efanesoctocog, which you had toward launch? And then 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 incidents here that you're seeing in the trial is below the evobrutinib Phase 3 trials, where around 26% of patients saw raised liver enzymes and 11% discontinued due to liver enzyme elevations? So in short, do you still see tolebrutinib as potentially differentiated on liver profile versus evobrutinib? Thank you.

Paul Hudson -- Chief Executive Officer

OK. Graham, thank you. We'll come to John in a moment. As for efanesoctocog alfa, and we look forward to sharing the brand name with you when it's approved, it's an interesting one, right? We haven't got to sharing price yet, but you jump in if you want to comment, but the efficacy is so good.

My own time at ISTH will really reinforce that. The important thing to remember is what worked against us with how [inaudible] uptake works for us with efanesoctocog. Because patients, if they want to move in this market, they will move. And so they'll get switched.

They'll get initiated. The momentum is patients wanting as normal life as possible. And so we are very excited about what we'll do with these meds. Bill, do you want to add anything?

Bill Sibold -- Executive Vice President, Sanofi Genzyme

No, I think that's right. I think a couple of things there favorable, as well as what we've seen globally, is still a recognition for innovation. And clearly, when you look in the hemophilia space, 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.

So we have high expectations. We're excited about it. We believe that there will be a path to reimburse them for it. And we believe that patients will want to -- and they will seek out a higher efficacy option.

Paul Hudson -- Chief Executive Officer

Thank you, Bill. John Reed, how about liver enzymes?

John Reed -- Executive Vice President, Global Head of Research and Development

Yeah, Graham. You're correct there. 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 evo, they've had double-digit numbers of -- percentages of patients that have had to go off study because of liver transaminase increases.

So we still believe that we have the strongest safety profile. And the other thing is that these cases always occur within the first couple of months of treatment. So the monitoring is important to do potentially in the beginning of the therapy. But after patients have been on therapy for a couple of months, if they haven't had one of these issues, they're going to be [inaudible].

As I said, we have 2,000-plus patients still on study and, up to this point, all well. So we think we've got a good plan for going forward with reducing the problem. And we'll work through getting this resolved with the FDA as expeditiously as possible.

Paul Hudson -- Chief Executive Officer

And maybe --

Graham Parry -- Bank of America Merrill Lynch -- Analyst

Sorry, John, the line just cut there. So did you say a few percent versus double digit for evobrutinib? Sorry, I just want to clarify that.

Paul Hudson -- Chief Executive Officer

No, it's at a fraction of 1%. That is what he said.

John Reed -- Executive Vice President, Global Head of Research and Development

As I mentioned [inaudible] and double digits for evo.

Paul Hudson -- Chief Executive Officer

We'll take few questions on it. Honestly, I mean, let's be really clear. I think we made the right changes to the protocol. We feel very good about that.

It was to find information to the regulator, and it's really basically just the U.S. And then we're heading to get this corrected, where the plans come off hold in Q4. That's what we're working toward. So OK, next question. 

Operator

Next question will be from Richard Vosser from J.P. Morgan. Richard?

Richard Vosser -- J.P. Morgan -- Analyst

Perhaps switching topics maybe 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 the -- in Europe and U.S. 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 may be 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.

Paul Hudson -- Chief Executive Officer

OK, good. Thank you. Maybe I can go to Julie in a moment, but Thomas, Fluzone High-Dose, and volumes?

Thomas Triomphe -- Executive Vice President, Sanofi Pasteur

Yeah. So overall, we're in a very good spot from a Fluzone supply perspective. Clearly, supply is not going to be any problem, as it's not been a problem for the past two years. And you know very well that we built capacity a few years ago to feel very confident.

And it comes at the time, as I mentioned, during the position of the ACIP recommendation. So 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. So it's not a small feat. And I expect, therefore, a good Fluzone High-Dose delivery, both in Europe and in the U.S.

So when we ship 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 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 reflects the quality of the supply we're getting.

Paul Hudson -- Chief Executive Officer

Thanks, Thomas. It's great work actually done by the vaccine team on the flu period season. So Julie, are people going from branded -- will people go from branded to generics with the pressure on people's pocket expenses? And maybe a quick comment on Tamiflu.

Julie Van Ongevalle -- Executive Vice President, Consumer Healthcare

Sure. Thank you, Richard, for your question. So first of all, what we've seen in healthcare is that share 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.

But we -- again, we've seen that in our area. Consumers and patients make the least compromises and, again, health is definitely most important. And efficacy and very strong -- is a very strong loyalty driver even -- again, even more so in healthcare. And 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, nothing has changed from the last quarter, is that we are waiting for the flu season to be able to start the new testing. So no news on Tamiflu so far.

Paul Hudson -- Chief Executive Officer

Yes. And thank you. Thank you, Julie. Also, maybe saying branded in the pharmacy.

Julie Van Ongevalle -- Executive Vice President, Consumer Healthcare

Of course.

Paul Hudson -- Chief Executive Officer

OK, next question.

Operator

The next question will be from David Risinger from Leerink.

David Risinger -- SVB Leerink Partners -- Analyst

Yes. Thanks very much. Can you hear me?

Paul Hudson -- Chief Executive Officer

Yes.

David Risinger -- SVB Leerink Partners -- Analyst

Great. So congrats on the performance. I have questions on tolebrutinib and amcenestrant. So 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 topline Phase 3 results from your global RMS studies? And then 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.

Paul Hudson -- Chief Executive Officer

OK. David, thank you. I think we've touched already a little bit on the tolebrutinib question on enrollments and submissions. But John, do you have anything extra to add?

John Reed -- Executive Vice President, Global Head of Research and Development

I just said we -- the RMS studies, we expect will read out the end of next year. And then the progressive studies would be the following year, which is pretty much on par with what we had originally forecasted. At this point, we are -- it is a global trial. It is actually our new series of trials, and this is the largest campaign that's ever been orchestrated for an MS drug.

So it is global. We do feel like we have the U.S. sufficiently covered. And I forget, what was the other --

Paul Hudson -- Chief Executive Officer

Yeah, amcenestrant, do you think we need to look at an ESR mutation to show a greater efficacy? Or should we just focus on the adjuvant setting where the opportunity is?

John Reed -- Executive Vice President, Global Head of Research and Development

Right. Well, actually, you'll be able to see the ESR mutant versus wild-type data at ESMO in terms of what we show in the late line setting. But in terms of the -- where we really have always felt the sweet spot to this mechanism in the adjuvant space, we were quite comfortable with the profile there, where there's a very small percentage of mutations in that setting and most patients still have wild-type receptor. And -- but we're active events, both wild-type, and mutant receptor.

So we sort of have our bases covered, I would say.

Paul Hudson -- Chief Executive Officer

OK. Thanks, John. Next question, please.

Operator

Yes. The next question will be from Mark Purcell from Morgan Stanley.

Mark Purcell -- Morgan Stanley -- Analyst

Great. 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? And how should we think about investment discipline here? I mean, Sanofi has now got so many new platforms to choose from, delivering new medicines through their firm intentions.

So a nice problem to have, but at 15% of sales in terms of an R&D margin, it was a nice offset potentially with gross margin, but it would be interesting to understand your own level of ambition there in terms of increasing investment in future innovation. And 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?

Paul Hudson -- Chief Executive Officer

OK. Thanks, Mark. So Jean, I think back to you. Actually, for that, maybe you'd like to make a commentary at the R&D investment levels.

Jean-Baptiste Chasseloup de Chatillon -- Chief Financial Officer & Executive Vice President

Yes. So there's no exact answer for the question. There's no magic number on -- maybe, by the way, you would consider consumer health within the equation because it isn't consumer as it's R&D-driven. But our vision is clear.

It's to increase within the -- so we expect our guidance is to increase as much as we can to spend on R&D. That's what we are doing. I know that sometimes it's -- I see the consensus that some are not believing us that we -- when we said we would add about EUR 0.5 billion this year in our P&L, that's what we are doing, and you see it in Q2. It's a clear proof point of our discipline in terms of being true to this commitment.

So I think, I repeat, no, no magic number, but the direction is clear.

Paul Hudson -- Chief Executive Officer

Thank you. Thanks, J-B. John, CEACAM5 ADC beyond one?

John Reed -- Executive Vice President, Global Head of Research and Development

Yeah. So we are pursuing that molecule for other CEACAM5 positive tumors, gastric, breast, etc. Still collecting data in those contexts. And then, of course, in lung, we're also in Phase 2 studies in frontline and coupled with pembro and exploring whether we can move into the frontline setting with that.

I thought the question was more broad about modalities in general. And 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. But our ability to support those from a CMC manufacturing, I feel we're quite confident we've been able to leverage our capabilities, for example, in microbial production of insulin to support the Synthorx platform, synthetic biology, which is the co-ag platform to support the Amunix platform to support the antibody platform where, again, we use microbial species. And all that's really been able to just kind of modify what we had available at our Frankfurt site there.

And then the other biologics platforms, we've been able to adapt to what we've had there. And then we're really leveraging a lot of capabilities in vaccines for some of the others. For example, the AAV platform, making viruses, live-attenuated viruses for vaccines is something our colleagues there know how to do for years, and we're actually doing our GMP production in the vaccines facility there and leveraging that. And of course, the commitment to the mRNA platform.

But the vaccines colleagues made is -- we just plug right into that for the therapeutics as well.

Paul Hudson -- Chief Executive Officer

Yeah. Thanks, John. Let me try and connect those chances together, actually, because it's really an interesting question. To J-B's point, our priority is to deliver our financial guidance increments.

And we worked really hard to reallocate R&D within that. So let's just be really clear because that's the goal within what we've committed. And outside of that, the platform piece, 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, more than half in antibodies. So we get a really efficient entry to have a shot at least proof of concept and beyond.

And I think we knew that was probably going to be our best way. But the real magic beyond the problem is when we start to converge the platforms. And that's why as we bring Amunix in, say, on top of antibodies, it starts to help us get to that [inaudible]. So there is individual platform opportunity and volume at scale as we get into our stride.

I think we're not far off. Then there's a convergence of the platforms that bring a lot of opportunity. And we work really hard as a team, the people on 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 final job.

OK, next question.

Operator

The next question will be from Keyur Parekh from Goldman Sachs.

Keyur Parekh -- Goldman Sachs -- Analyst

Hi. Thanks 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 OK from an FDA perspective? Secondly, kind of just looking at the consumer health business, clearly, kind of demonstrating very strong execution and continued growth.

But your guidance assumes kind of much more deceleration in growth toward the second half of the year. Just wondering, beyond tougher comps, is there anything else you are seeing from an end market perspective that is driving or should we think of it as classic Sanofi conservatism on this guidance over here? Thank you.

Paul Hudson -- Chief Executive Officer

I didn't quite get the second question, but [inaudible] is going to 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 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. So if there's anything more to add to that, any point?

John Reed -- Executive Vice President, Global Head of Research and Development

Yeah. 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 the all-around study, including in the United States. So all those patients continue to be followed and until the outcome of the study. So I think just remember that.

Also, we didn't reemphasize here, but it probably merits that the liver injury cases we saw were reversible. Nobody went to transplant. Nobody died. I mean they were picked up by a routine monitoring.

So we feel like if we can address this, we've got to just give the FDA their checklist of things that they want as additional recurrences.

Paul Hudson -- Chief Executive Officer

Thanks, John. J-B, are you being conservative?

Jean-Baptiste Chasseloup de Chatillon -- Chief Financial Officer & Executive Vice President

OK. Keyur, are you having a go at me?

Keyur Parekh -- Goldman Sachs -- Analyst

No.

Jean-Baptiste Chasseloup de Chatillon -- Chief Financial Officer & Executive Vice President

No. I see, I've had more -- I have more insight than you have, and we don't see anything outside that you can see. So we're very transparent what we -- results that we gave for the second half of the year. And we're raising our guidance.

That summarized it, and so conservative, we are.

Paul Hudson -- Chief Executive Officer

OK.

Julie Van Ongevalle -- Executive Vice President, Consumer Healthcare

I think there was a question on consumer and on how we see the remainder of the year. I think, what's important, so 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 12-month rolling basis. Looking ahead, after this 5th, 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 market overall, and we did, too, a higher 2021 comparison, but we still have the ambition to continue to grow in line or slightly ahead of the market. I hope that answers your question.

Paul Hudson -- Chief Executive Officer

Yeah. Thank you. All set. OK.

Where are we?

Operator

Next question, Tim Anderson from Wolfe.

Tim Anderson -- Wolfe Research -- Analyst

Thank you. A couple of questions. On Dupixent, and it's really on China. In China, there's at least one look-alike product moving into Phase 3.

And in certain categories, we've seen fast follower products kind of cause headaches for multinationals. So 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 nearer term? And then second question on tolebrutinib. Just back on LFT elevations. I know that frequency is lower.

Any of those grade 3 or grade 4? Have any other countries besides the U.S. put the drug on clinical hold?

Paul Hudson -- Chief Executive Officer

OK. Well, now I'm going to throw to you, Bill, to be -- in China. And I think, at this point, we've asked -- we've answered all the tolebrutinib questions. I understand, as we get more information, we'll share with you as we get into Q3.

But getting off the hold is the priority, and we'll update you. Bill, anything to add on China? China is part of the waypoint of EUR 13 billion and/or the fast follow-up to market.

Bill Sibold -- Executive Vice President, Sanofi Genzyme

It is. It certainly is long. I think what we've also said is that we expect it to be a blockbuster in its own right in China. So 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 successful with and positive data reads -- readouts that's early with some -- another asthma trial there. So yes, we think that within China, any follower is going to have to, first of all, compete against the product, which has kind of opened up the AD market in China.

We expect that -- we have high hopes that there will be a recognition of the IP that exists within China. And we think that the expertise that we brought to the market will be recognized. And as we get more information on it, we're not even certain, if anything, will come at this point. But we -- as I said, it's baked into our EUR 1 billion-plus forecast that we have and the waypoint of EUR 13 billion that Paul said.

Paul Hudson -- Chief Executive Officer

Yeah. Maybe I think it started really well, I mean, really well.

Bill Sibold -- Executive Vice President, Sanofi Genzyme

Yes. Great start. Unprecedented start, really, for a biologic.

Paul Hudson -- Chief Executive Officer

That's why I think we ought to -- maybe I think we should share time line launches in China, we'll get in a moment, and it's a rocket ship. And then even after the lockdown, we haven't had a chance to comment about it today, but patients coming literally spread back out and getting to see the dermatologists.

Bill Sibold -- Executive Vice President, Sanofi Genzyme

That's right.

Paul Hudson -- Chief Executive Officer

And so it bodes well, bodes really well. OK, next question, please. 

Operator

Yes. The next question will be from Laura Sutcliffe from UBS.

Laura Sutcliffe -- UBS -- Analyst

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? And secondly, could you maybe just tell us why you've discontinued dupilumab in peanut allergy? Thanks.

Paul Hudson -- Chief Executive Officer

OK. Well, John, I'll come to you on peanut allergy.

John Reed -- Executive Vice President, Global Head of Research and Development

OK.

Paul Hudson -- Chief Executive Officer

And Bill, maybe just a general comment about rilza, the oral, the approach and then maybe I think you further answer that then open to John.

Bill Sibold -- Executive Vice President, Sanofi Genzyme

Yes. No, thanks for the question. So look, let me start with ITP. There's about 25,000 chronic ITP adults in the U.S.

that are eligible for the second-line plus treatments after steroids. So 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 to be a fast onset of action and durable effect that took place.

So we'll continue wait for the data, so to speak. But we see that as a nice potential. And also 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 [inaudible], etc.

So this is one of those products that we think is so fundamental, the 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, rilza, it allows us to go to other places as well. So quite promising in an ITP, specifically strong data, fast onset of action, durable effect.

Paul Hudson -- Chief Executive Officer

OK. Thanks, Bill. So John, any comment on peanut allergy?

John Reed -- Executive Vice President, Global Head of Research and Development

Well, I can tell you that it's really difficult to do good clinical trials in that space. We did do some Phase 2 kind of exploratory work. Just decided it was not ranking as high on our strategic priorities. There's other places we could invest in, so we kind of just let it stay there for now.

Paul Hudson -- Chief Executive Officer

OK. Thank you. OK, next question, please.

Operator

Next question is from Gary Steventon from Exane.

Simon Mather -- Exane BNP Paribas -- Analyst

Hi. Yes. Sorry. This is Simon actually, apologies.

Apologies for that. Two questions and none on tolebrutinib. Firstly, a follow-up on the margin question, if you could. I mean, you're able to consistently overdeliver with the strong results despite your commitment to meaningfully increase your investment in R&D.

I'm thinking, just taking into account your prior commentary around meaningful Dupixent gross margin step-up from '24, 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 -- in the more than 32% operating targets for 2025? And just a quick follow-on. Can you quantify the remaining R&D spend that has to be repaid by Regeneron? And 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 [inaudible]. I'm just wondering if you could potentially share your thoughts on your exposure in light of his remarks that Zantac could potentially draw from that.

Thank you.

Paul Hudson -- Chief Executive Officer

OK. Simon, thank you. So let's start with J-B and then get to Julie.

Jean-Baptiste Chasseloup de Chatillon -- Chief Financial Officer & Executive Vice President

Yeah. Sorry, Simon. I'll have just to repeat the same message. We will increase our R&D spend as much as we can if we have room to do it because you see our portfolio.

You see there's a need for innovation, and we want to stand by this commitment. Yes, on the total impact, as an indication, I can tell you that we will not have finished to have toward this accelerated repayment. It will impact us, at least, through '26. So yes, it's a very significant amount of R&D that we will see coming back through the acceleration of the development balance, and that's great.

That means that we can invest in more innovation.

Paul Hudson -- Chief Executive Officer

Thank you. Julie, do you make some comments on Zantac?

Julie Van Ongevalle -- Executive Vice President, Consumer Healthcare

Sure. So first, I want to remind that Sanofi voluntarily withdrew the OTC Zantac from the market in '19 and Zantac OTC products containing ranitidine remain of 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. So we're confident.

Paul Hudson -- Chief Executive Officer

OK. Roy, do you want to add anything?

Roy Papatheodorou -- Executive Vice President, General Counsel

I think Julie covered it well. There's no reliable evidence whatsoever that Zantac causes cancer. The amounts are stuff that's found in ingredients of common foods, and we feel very strongly about our defenses. And also, we acted responsibly -- more than responsibly at all times.

Paul Hudson -- Chief Executive Officer

OK. Thank you. Next question, please.

Operator

Yes. The next question will be from Simon Baker from Redburn.

Simon Baker -- Redburn -- Analyst

Thank you very much for taking my questions. Two, if I may, one on vaccines and one on consumer. And also, just a quick clarification on Fluzone flu record year, Thomas. Is that record year in terms of just value or volume and value? And the main question on vaccines was you indicated that you have data for the COVID booster against Omicron BA.1.

I just wondered, this is still fairly early stage, if you have any data against BA.4 and BA.5? And 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 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 that -- the pulls and pushes on that.

If you could give us some color, that would be very helpful.

Paul Hudson -- Chief Executive Officer

OK. Thank you, Simon. So Thomas, then record, we see split between value and volume, of course, and you heard it, it was either BA.4, 5 with [inaudible].

Thomas Triomphe -- Executive Vice President, Sanofi Pasteur

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. So each time we are talking about record full year, it's about sales.

And especially, as we 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. So we're 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. So 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. So we believe it's a good opportunity for public decision-makers.

Paul Hudson -- Chief Executive Officer

Thank you, Thomas. Julie, I'm not sure how you normally break price down publicly, if you choose not to share, it's OK, by region.

Julie Van Ongevalle -- Executive Vice President, Consumer Healthcare

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 cost, the competitive behavior by region, as well as the consumer elasticity. And all regions have increased prices.

Paul Hudson -- Chief Executive Officer

Thank you. And J-B, gross margin?

Jean-Baptiste Chasseloup de Chatillon -- Chief Financial Officer & Executive Vice President

Yes. Well, so margin of -- what we achieved in terms of gross margin, first, part of the business that we can reprice but there are headwinds, so it's maintaining quite well. We see that across the board on the regions. In terms of overall stability of the margin, of course, you cannot read through our current sectorial publication the effective level of margin as it is that will be externalized more something like next year.

Paul Hudson -- Chief Executive Officer

OK. Thank you. Next question, please.

Operator

Yes. The next question will be from Seamus Fernandez from Guggenheim.

Seamus Fernandez -- Guggenheim Partners -- Analyst

Yeah, thanks. Can you just -- hoping you guys could update us on amlitelimab and the progress toward hopefully entering registrational trials. Maybe you can just talk a little bit about the differentiation that you see on that product as well. I know it's core to the continued attempts toward dominance in the immunology space.

So 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 I didn't know if we might see advancement into a pivotal sooner than that. Thanks.

Paul Hudson -- Chief Executive Officer

OK. Thanks, Seamus. John, whether we have the winner with OX40-Ligand.

John Reed -- Executive Vice President, Global Head of Research and Development

Yeah. Let me maybe do the differentiation first and then cover where we are with aspiration to accelerate. On the differentiation of -- as you know, we're targeting the ligand, whereas others are targeting the receptor. And there -- a reason to believe that could be better from the standpoint that the ligand is prevalently at lower levels, and you have less problem really covering the full target and getting good target exposure, we believe.

But more importantly, probably is that amlitelimab is a nondepleting antibody. It doesn't kill the cells that express the ligand, whereas the competitor molecule that binds the receptor actually kills the cells. And 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 immunosuppressant cells that you need for immune homeostasis. We also think because that is a depleting antibody that activates and 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 of 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 efficacy, but also the safety database that will be required, etc. We want to make sure that the study population does represent the diversity of patients that struggle with atopic dermatitis, both in terms of what therapies they've experienced, as well as, of course, the D&I types of issues around representation.

So we're really working with the 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.

Paul Hudson -- Chief Executive Officer

OK. So I think -- thanks, John. So I think, just mechanistically, we have the advantage. I think we want to get there as soon as we can.

We're ambitious. We told you that. We're looking for all the opportunities to do that. And when we can confirm that, we will do that.

But it's going to be really important to make sure everybody else ties the full benefit of what this medicine can do and have the opportunity to be with the team. We were able -- among the team last week, and it's starting to get really exciting. So I really appreciate the question, Seamus. Do we have time for one more?

Operator

One more. The last one will be from Peter Verdult from Citi.

Peter Verdult -- Citi -- Analyst

Yeah. Thanks, everyone. Peter Verdult from Citi. Two questions, just for Paul first.

It's been three years since the play-to-win strategy was laid out. You're obviously you 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 put it toward top-line growth aspirations rather than staying focused on BOI and margins and free cash flow? And then second, very quickly, for John on the pipe. IRAK4, is this asset still viable in light of the recent data we saw highlighting a QTc signal?

Paul Hudson -- Chief Executive Officer

Excellent questions. So some reflections maybe in three years. I think it's incredible the speed of transformations in these companies and the people in these companies, incredible in doing incredible things. So obviously, we're ahead of where I'd hoped in the weeks leading that to join in.

I think we have to earn the right to move to that sort of top line through. We have to deliver the science. We have to deliver the guidance. And we said back in '19, we would earn the credibility from delivering exactly what we said we would do.

And so we doubt that's nonnegotiable for us. And we think we're building quite a high degree of trust on that. Maybe there'll become a moment where we get to look further ahead is, of course, you'd expect that, and to be bold about what that looks like for us. Because, of course, investments in R&D, that's an important consideration over the long term.

But 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'll do. As for IRAK4, it's pretty fast inning, which took just a little bit on rilzabrutinib earlier.

In biologic-dominated marketplaces, there are rooms for beautifully put-together orals. It's been a holy grail for most companies and most diseases. It's a needle to thread. You have to remember that the goal is not always to be as good as a biologic than to be a relevant medicine on the journey to a biologic.

And so we know what you have to look like to be a successful oral and the volume, too, is to slightly earlier in diseases. It's nothing like some of the and oral in psoriasis. You have to think in those terms. So we remain enthusiastic about the IRAK4 makers, and we're working with the teams on making sure that we -- because we're careful and judicious about where we spend our R&D dollars, that we think we would have a profile that could be meaningful share-wise in the market.

And so 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, patient populations, different methods of delivery. So I think, yes, thanks, Peter, for that. That's a good way to maybe to bring it to an end, if that's OK.

Thanks to the team. Thanks to everything that people are doing. So -- and 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.

Duration: 0 minutes

Call participants:

Eva Schaefer-Jansen

Paul Hudson -- Chief Executive Officer

Bill Sibold -- Executive Vice President, Sanofi Genzyme

Thomas Triomphe -- Executive Vice President, Sanofi Pasteur

Olivier Charmeil -- Executive Vice President, General Medicines

Julie Van Ongevalle -- Executive Vice President, Consumer Healthcare

Jean-Baptiste Chasseloup de Chatillon -- Chief Financial Officer & Executive Vice President

Wimal Kapadia -- AllianceBernstein -- Analyst

John Reed -- Executive Vice President, Global Head of Research and Development

Jo Walton -- Credit Suisse -- Analyst

Graham Parry -- Bank of America Merrill Lynch -- Analyst

Richard Vosser -- J.P. Morgan -- Analyst

David Risinger -- SVB Leerink Partners -- Analyst

Mark Purcell -- Morgan Stanley -- Analyst

Keyur Parekh -- Goldman Sachs -- Analyst

Tim Anderson -- Wolfe Research -- Analyst

Laura Sutcliffe -- UBS -- Analyst

Simon Mather -- Exane BNP Paribas -- Analyst

Roy Papatheodorou -- Executive Vice President, General Counsel

Simon Baker -- Redburn -- Analyst

Seamus Fernandez -- Guggenheim Partners -- Analyst

Peter Verdult -- Citi -- Analyst

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