Sanofi - Earnings Call - Q3 2025
October 24, 2025
Transcript
Thomas Kudsk Larsen (Head of Investor Relations)
Hello everyone, this is Thomas Kudsk Larsen from the Sanofi IR team. Welcome to the Q3 2025 conference call for investors and analysts. As usual, you can find the slides on sanofi.com. Please turn to slide number three. Here we have the usual forward-looking statements. We would like to remind you that information presented in this call contains forward-looking statements that are subject to substantial risk and uncertainty that may cause actual results to differ materially. We encourage you to read the disclaimer in our slide presentation. In addition, we refer you to our Form 20-F on file with the U.S. SEC and our French Universal Registration document for a description of these risk factors. As usual, we'll be making comments on our performance using constant exchange rates and other non-adverse measures. Numbers used are usually in millions of euros and for Q3 2025, unless we state otherwise.
Please turn to slide number four. First, we have the presentation, and then we take your questions. As usual, we aim at keeping it all to one hour, including questions. For Q&A, we have Olivier, Brian, and Thomas to cover our global businesses, as well as Roy, our General Counsel, and Brendan, Head of Manufacturing and Supply. For the Q&A, you have two options in Zoom: raise your hand or submit your question using the Q&A function. With this, I'll hand you over to Paul on my left-hand side.
Paul Hudson (CEO)
Thanks, Thomas. Thank you, everyone, for joining us today. Our growth momentum continued in Q3 with EUR 12.4 billion in sales, up 7% over last year's high base of comparison. Sales growth was primarily driven by our new launches and the performance of Dupixent, which reached EUR 4 billion in quarterly sales for the first time. After the third quarter performance, we are confident in the business outlook for the remainder of the year and reiterate our full-year 2025 sales guidance. This positive outlook includes our expectations for the business in the U.S., our largest market by sales. We continue to work with the administration and policymakers in the U.S. and around the world on policies that improve access to treatments, lower prices for patients, and improve health systems and protect science.
Our recent announcement on the expansion of our patient affordability program, offering improved access to all our insulins, is a great example of this work, which I'll discuss in a little more detail later in the presentation. Now, let me highlight the contribution of our new launches, which have been a significant driver of this quarter's strong performance. Our launches delivered EUR 1.8 billion this quarter, with more than 40%, and now represent 15% of our total sales. To put this in perspective, our launches represent almost half of Dupixent sales this quarter, demonstrating their significant contribution to our growth. We've strengthened our commercial portfolio with three new additions: Ayvakit, our medicine for both advanced and indolent systemic mastocytosis; the first Sanofi sales of Nuvaxovid, offering an important protein-based and non-mRNA alternative for COVID-19 vaccination; and Wayrilz, our new BTK inhibitor designed as a multi-immune modulator.
This innovative medicine provides a new option for patients with immune thrombocytopenia that extends beyond their platelet count needs to addressing quality-of-life burdens. We're seeing good uptake across our portfolio of new medicines and Beyfortus, which achieved blockbuster status last year in its first full year of sales, continues its expansion into new geographies. Altuvio is on track to reach blockbuster status this year, and Ayvakit could become our next blockbuster in 2026. Dupixent has reached a new milestone this quarter, exceeding EUR 4 billion in quarterly sales for the first time. More than eight years after its initial launch in atopic dermatitis, we saw an increase of over 30% in the number of patients during the last 12 months. In the U.S., we've surpassed the EUR 3 billion quarterly sales mark, maintaining leadership in both new and total prescriptions across established indications.
Our launches in the recently approved indications COPD, CSU, and BP are progressing as planned. Outside the U.S., sales grew 21%, exceeding EUR 1 billion in the quarter. We continue our efforts to make Dupixent available to more patients, helped by the positive CHMP recommendation for CSU in the EU and regulatory submission for CSU in children in the U.S. and EU. Turning to our vaccine business, Q3 sales were EUR 3.4 billion. This performance compares to a high base in the previous year and reflects the competitive price pressure, as well as a lower flu immunization rate in the U.S. A new highlight among our respiratory vaccines is the early start of Nuvaxovid, the only non-mRNA COVID-19 vaccine available in the U.S. and from our collaboration with Novavax. First shipments of Nuvaxovid were delivered in the U.S. in September.
In Beyfortus continues its impressive expansion, up 20% this quarter, and now available in 40 countries. As you may have seen in our press release this morning, we decided to discontinue our RSV toddler program. While the safety profile was acceptable, the predetermined criteria for efficacy was not met in the planned futility analysis. The PPH and booster franchise remains an important contributor to our vaccine business, with the performance in Q3 reflecting phasing in the first half of the year. Sanofi has a proud legacy in flu vaccines, and we remain committed on bringing innovation to strengthen our leadership in flu and to provide better protection for patients. Our FLUNITY-HD study published in The Lancet last week demonstrated that our high-dose flu vaccine, Efluelda, known as Fluzone HD in North America, provided superior protection versus standard dose vaccine on the sometimes devastating consequences of flu.
Data showed an 8.8% reduction in pneumonia or flu hospitalizations and an important 32% reduction in laboratory-confirmed flu hospitalizations versus standard dose vaccines. We are expanding access to this beneficial protection with positive Phase III data that support a label update, extending the age down to 50 years for Efluelda Fluzone HD. Looking ahead, we're advancing our flu pandemic preparedness with two programs, while improving vaccination convenience with positive data on flu-COVID combination vaccines. These achievements underscore our commitment to delivering enhanced protection against respiratory viruses to more people worldwide. In addition to our unwavering commitment to innovation in respiratory viruses, we're also steadfast in our commitment to improve patients' access to healthcare.
Our Global Health Unit has reached a remarkable milestone: 1 million patients treated for non-communicable diseases across more than 40 low and middle-income countries since 2021, putting us on track to reach 2 million patients by 2030. We trained over 27,000 healthcare workers and reached 4 million people through our partnership programs during this same period. We're not stopping there. In the U.S., we're expanding our insulins value savings program to ensure every American has access to our insulins at just $35 per month. This initiative builds on Sanofi's longstanding efforts to provide patients access to a reliable and affordable supply of critical medicines. Thank you, and I will now hand over to François, our CFO, for more details on the financials.
François-Xavier Roger (CFO)
Thank you, Paul, and hello to everyone. In Q3, our med sales grew by 7% at constant exchange rates. This growth was primarily driven by pharma and more specifically by immunology and recent launches. Our new launch is demonstrating a strong momentum with 41% sales growth, while Dupixent sales grew by 26% this quarter. Vaccine sales were down, primarily due to flu, as expected. This decrease resulted from a combination of competitive price pressure, mainly in Germany, and lower vaccination rates. At published rates, net group sales increased by 2%, impacted by a negative foreign exchange effect. These solid results highlight our ability to drive growth against headwinds. Our business gross margin increased by 2.3 percentage points this quarter, with a continued improvement in product mix, enhanced by productivity gains.
We now capture the full benefit of Dupixent's improved manufacturing process, as well as a contribution from Ayvakit since the Blueprint closing in mid-July. As we move into 2026, the gross margin profile will return to its fundamental growth as the step up from Dupixent's C3 manufacturing transition is now complete. Operating expenses grew by 6%. Excluding the impact of the Blueprint acquisition, operating expenses grew by low single digit, highlighting our cost discipline. R&D expenses increased by 5%, broadly reflecting the underlying activity level. We continue to invest in sales and marketing to support our launches, and G&A costs were slightly down, in line with our objective to keep them broadly stable going forward. Other operating income and expenses are moving up, primarily due to the increased share of profits paid to Regeneron as Dupixent continues its strong growth trajectory.
Business EPS reached EUR 2.91, a robust growth of EUR 0.19 and 13% compared to Q3 2024. This strong performance reflects our compelling sales growth and increasing gross margin, combined with cost discipline. Looking at our year-to-date progress, we are maintaining stronger earnings momentum with 9% sales growth and business EPS growing faster at 12%. It fully supports our guidance for the full year and demonstrates our ability to deliver profitable growth consistently. Based on our year-to-date performance, we reiterate our full-year guidance of high single-digit sales growth and low double-digit business EPS growth at constant exchange rates. We have now completed the acquisitions of Drensbios DR0201, Vigil Neuroscience, and Blueprint, and their associated costs are fully factored in our guidance. While we typically provide full-year guidance at the beginning of each year, we can share a few business trends for next year, which you may find useful for modeling purposes.
R&D next year is expected to increase moderately. We will continue investing in sales and marketing to support our product launches, as well as our strong sales momentum. At the same time, we will remain disciplined on G&A costs, with the objective to keep them broadly stable. We expect to achieve around EUR 500 million of capital gains from divestment, similar to what we anticipate for 2025. Regarding Amvuttra royalties, based on the latest evaluated pharma sales consensus, the implied royalties are now expected around EUR 700 million for next year. You will find a slide with the updated Amvudra royalty considerations reflecting current external consensus in the appendices of this presentation. Another indicator for 2026 is a reduction of approximately EUR 300 million reimbursement from Regeneron for the R&D balance. Both items, Amvuttra gains and Regeneron R&D reimbursement, will offset each other next year.
We continue to execute our capital allocation policy and will remain disciplined and balanced across four priorities: investing in organic growth drivers, pursuing selective bolt-on acquisitions, maintaining our policy of progressive dividends, and executing opportunistic share buybacks. Based on our projected trajectory for 2026 and beyond, we remain confident in our ability to sustain our profitable growth momentum for the next few years. I now hand over to Houman to provide an update on the progress of our innovative pipeline.
Houman Ashrafian (Head of R&D)
Thank you, François. I'm pleased to share our Q3 pipeline achievements with progress in many programs. We received regulatory approvals for Wayrilz in the United States, in ITP, and Tzield in China. Further, we received regulatory submission acceptances for Dupixent CSU in children in the U.S. and in the EU. The FDA nominated Tzield for the new Commissioner's National Priority Voucher Program to speed up the review. Wayrilz ITP was submitted in Japan, and Sarclisa subcutaneous was accepted globally in myeloma. Our Phase III programs have delivered successful readouts, with amlitelimab meeting the primary endpoints in the Phase III study in atopic dermatitis dose one and Fluzone HD in people 50 years and above. We also commenced dosing first patient in new Phase III studies, one of the two studies for lansecamig in COPD and Wayrilz in sickle cell disease and warm autoimmune hemolytic anemia.
Finally, Wayrilz is emerging as a multi-immune modulation platform in rare diseases, with an approval in the U.S. and a positive recommendation in the EU for ITP. Multiple designations across new indications further strengthening our rare disease portfolio. Please turn to the next slide. Moving to dermatology, amlodipine met all primary and secondary key endpoints in the first Phase III study in AD. Data demonstrated clinically meaningful improvement in several measures of skin clearance. As an example, looking at the vIGA measure, the efficacy progressively increased and showed no plateau at 24 weeks. Further, amlitelimab offers patient-friendly quarterly dosing. There were no new safety concerns identified in this study. Oceana AD is a comprehensive program, including five Phase III studies in adults and adolescents, biologic experienced patients, and across different geographies. We anticipate full data to report out throughout 2026.
Brivekimig, TNF-α, and OX40 ligand nanobody achieved its primary objective in a Phase IIA study in HS. We observed clinically meaningful improvements in both primary and secondary endpoints in biologically naive patients at week 16. Brivekimig was well tolerated. Data were presented at EADV in Paris in September, where I also had the pleasure to meet many of you at our IR roundtable. Our Phase IIB study is now starting its recruitment. Please turn to the next slide. Moving to respiratory, amlitelimab has shown intriguing efficacy in its Phase II study in asthma, particularly in a difficult-to-treat subgroup. While the primary endpoint of annualized asthma exacerbation rate reduction at week 48 did not reach statistical significance at the highest dose, notable improvements were observed in the secondary endpoints.
The heterogeneous inflammation subgroup of patients with high blood eosinophils of greater than 300 cells per microliter and elevated neutrophils at greater than 4,000 cells per microliter showed the greatest benefit. Treatment was well tolerated, with no new safety concerns. We're still analyzing study data, including biomarkers. Next steps will be subject to prioritizations within our overall respiratory portfolio. We're pleased by the recent efdoralprin alfa data, which showed superiority to the standard of care in the phase two study, the alpha-1-antitrypsin deficiency emphysema. The recombinant protein has a longer half-life and can provide higher AAT serum levels with less frequent dosing of either once every three or four weeks. A Phase II open-label study is currently ongoing, which will add to the safety data.
We will now engage in discussions with regulatory agencies to see if we can move ahead based on the data we have, supported by the upcoming safety studies. Please turn to the next slide. Pb212-DOTAMTATE, our radioligand, showed intriguing overall response rates in patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors, otherwise known as GEP-NETs, a group of difficult-to-treat rare endocrinological cancers. In peptide receptor radionuclide therapy naive patients, the overall response rate was 57.1%, and in PRRT-exposed patients, the overall response was 19.2%. Both measures were based on blinded independent central review. We observed a manageable safety profile that was similar across both cohorts. In immunology, our oral TNF balinatunfib didn't meet the predefined primary endpoint of ACR20 but showed clinically meaningful efficacy in a Phase II study in uncontrolled advanced treatment-naive rheumatoid arthritis patients on background methotrexate across endpoints requiring a deeper disease control, including ACR50 and ACR70.
This oral treatment has the potential to be used as a combination backbone therapy with internal and external oral medicines, with the next step currently being evaluated. Finally, we're close to initiating two replicate Phase III studies for duvakitug in both Crohn's disease and ulcerative colitis. This treatment offers patient-friendly subcutaneous dosing with a potential competitive safety and efficacy by selectively targeting the DC3 receptor. This follows the positive Phase II data that read out last year and were presented at the ECHO meeting this year. Next slide, please. As a conclusion, let me share a status of our key mid and late-stage development projects.
Our immunology pipeline includes medicines with available data, such as amlitelimab Phase III program in AD, with further potential lifecycle management, lunsekimig in Phase II in different asthma patient subgroups, and potential LCM, such as COPD, as well as brivekimig in HS and others in mid-stage development, some of which I covered earlier, like balinatunfib and duvakitug. On itepekimab, I can share that a decision to move forward in COPD will be made subject to regulatory discussions and in collaboration with our valued partner, Regeneron. In rare diseases, Wayrilz is now approved for ITP in the U.S., with potential for multiple new indications, venglustat, currently in Phase III for Fabry disease and Gaucher's disease type 3, and lastly, efdoralprin alfa, successful in Phase II for alpha-1 antitrypsin deficiency, with encouraging update just the other day.
Sarclisa is well underway with a subcutaneous formulation already approved across different lines and combination regimens in multiple regions and Pb-212 DOTAMTATE in GEP-NETs with data this week at ESME. In neurology, tolebrutinib is in review for SPMS with a revised PDUFA date of December 28, and in Phase III for primary progressive multiple sclerosis, with a readout before the end of the year. Frexalimab is in Phase III for relapsing remitting multiple sclerosis in SPMS-2, and lastly, riliprubart in two Phase III studies for chronic inflammatory demyelinating polyneuropathy. Finally, in vaccines, we have multiple Phase III programs underway, such as rabies, [BCV21], yellow fever vaccines, and broad opportunities in flu. Flu, COVID combinations, and pandemic flu right behind, as Paul covered earlier in his slides. Next slide, please.
On my last slide, I plan to cover my usual newsflow slide for the remaining three months of the year and all of 2026. The last significant items of 2025 are U.S. decisions on palibrutinib in SPMS and Phase III readouts in PPMS and multiple regulatory decisions. Next year, we expect the remaining Phase III readouts for amlodipine in AD. In rare diseases, we also expect venglustat Phase III readouts in two indications. In all cases, if positive, regulatory submissions will follow later in the year. In addition, we anticipate multiple regulatory submissions based on data we have already received this year, as well as regulatory decisions for medicines and vaccines under review.
Before I close, my sincere thanks to all colleagues in Sanofi R&D who share my commitment to improve science in Sanofi and help advance our pipeline further, from the new initiatives and research all the way to regulatory approval. With this, I hand back to Paul.
Paul Hudson (CEO)
Okay, thank you, Houman. We'll now open the call to your questions. As a reminder, we would ask you to limit your questions to one or two each. You'll be notified when your line is open to ask your question. At that time, please make sure you unmute your microphone. Option two, submit your question by clicking the Q&A icon at the bottom of the screen. The question will be read by our panelists. Now, we will take the first question. Please go ahead.
Operator (participant)
Yeah, it's the first question from Sachin Jain from BofA.
Sachin Jain (Analyst)
Hi there, thanks for taking my questions. First, I wonder if you could just update us on the Poly-SPMS regulatory debate and confidence resolving any questions the FDA has had with that delayed PDUFA. The second one, just to make sure there's no confusion in the market given the debate at 2Q, can we assume that your wording of profitable growth for 2026 means EBIT and EPS ahead of sales? Thank you.
Paul Hudson (CEO)
Okay, thank you. Do you want to provide some clarity on the regulatory piece on the SPMS colibrutinib?
Houman Ashrafian (Head of R&D)
Yeah, thanks for the question. Pretty straightforward. As we reported earlier in the year, the FDA requested an extension. We've submitted data sets with the FDA, continue conversations, and look forward to the PDUFA December 28th?
Paul Hudson (CEO)
Thank you. François.
François-Xavier Roger (CFO)
Yes, on profitable growth, I confirm that the idea is to have, as we go down through the P&L, all items growing faster than at the upper end of the P&L, which means basically gross margin growing faster than sales growth, BOI growing faster than gross margin, and EPS growing faster than BOI. We have achieved that each and every single quarter this year. We'll do it in 2025. We expect to get there in 2026, and we are working in the summer to deliver the same objective for the following years as well.
Paul Hudson (CEO)
That's very clear. Thank you, François. Next question.
Operator (participant)
Next question is from Luisa Hector from Berenberg. Luisa.
Luisa Hector (Analyst)
Thank you. Perhaps I could ask the obligatory U.S. policy question. Do you have any updates on your conversations with the U.S. administration? Is it more complex for you with shared assets like Dupixent? Should we be concerned about a degree of silence right now, or is it simply that there is more of a bottleneck in terms of a long queue to speak with the administration? Maybe Trump's busy agenda, just any color on that sort of ability to communicate. I'll stop there. Thank you.
Paul Hudson (CEO)
Thank you. I think our answer is pretty straightforward, which is we've had ongoing dialogue with the U.S. government and indeed multiple governments since before we received the letter, back at the end of July, I think it was. We focus on making sure that people understand the value we can bring, and those conversations have continued throughout this whole process. You could probably comment on bottlenecks or other implications, but I think that's probably as much as we can say at this point. Okay, thank you, Luisa. Next question, please.
Operator (participant)
Yes, next question, Shirley Shin from Barclays. Shirley?
Shirley Shin (Analyst)
Hi, can you guys hear me?
Paul Hudson (CEO)
Yeah.
Shirley Shin (Analyst)
Hi, thank you so much for taking my question. I have a question Beyfortus. as you guys said, the Q3 orders have been impacted by inventory carryover from last season. Could you please give us a sense of how Q4 ordering trends are tracking so far? Are we still expecting a 3Q, 4Q equal split? Also, given the competition that is ongoing, how do we see the trend? Will we map competition? Is it going to impact the 4Q number, given we know that Merck actually entered the market late-ish in 3Q? We saw very strong growth in the ex-U.S. market. What do you see the opportunities there? What is your overall perspective Beyfortus in 2026? Thank you.
Paul Hudson (CEO)
Okay, so the four questions, Tom, are for you.
Thomas Triomphe (Head of Vaccines)
That is a rich question. Thank you very much, Shirley. Maybe a couple of points to address these different elements. Thank you for giving an eye to Beyfortus performance in Q3. As you noticed, a few points of highlight. First of all, overall Beyfortus, you saw that we increased our performance versus last year. We have done that notably by extending the penetration to about 40 countries. In your question, there were some geographic elements to it. On the U.S. part, yes, absolutely, you're correct on what's going on in the U.S. Yes, we do confirm the guidance that we had provided at the last quarter at Q4. We expect it to be roughly in the same order of magnitude as Q3 Beyfortus overall, for Beyfortus performance. The second point, I think you wanted to mention a couple of points on the environment and the competition.
Without talking about the competition specifically, because we don't do that, maybe I can say a few words on the fact that actually, if you look at last year, 2024, the first year of full supply, Beyfortus was a blockbuster. You remember that if you look at the U.S. performance, the total, I will say, coverage rate of all babies in the U.S. was around 55% for all RSV solutions available. Roughly 55% of babies were getting some form of RSV protection. We really focused in 2025, and I think we will be focusing in 2026, to increase that vaccination coverage rate. We expect 2025 to land around 70% vaccination coverage rate in the U.S. That is why we are welcoming all efforts from everywhere to make sure that we increase the importance of awareness. What we are seeing in the signals in the U.S.
is that by Beyfortus is the favored product, the favored prescription from U.S. prescribers, simply due to the fact that it's highly differentiated. With an extended half-life of 71 days, it makes it by far the longest-acting monoclonal antibodies for the prevention of RSV. It has an incredible real-world evidence behind it. That is very important moving forward.
Paul Hudson (CEO)
Okay, thank you. Next question, please.
Operator (participant)
Yes, next question, Matthew Weston from UBS. Matthew?
Matthew Weston (Analyst)
Thank you. Two questions, please. François, I'm going to buck the trend. Most people ask 2026 guidance questions. I'm going to ask a 2027 guidance question. Slide 29 flags the Regeneron R&D reimbursement stepping down. It's something that's been familiar, I think, for many people for a while, but maybe not fully reflected in consensus. The step-down is actually much greater in 2027 than in 2026. Your slide implies about EUR 500 million EBIT gap in 2027. I'm just trying to understand, are there any additional levers within manufacturing, gross margin, or the business that could help mitigate that? Or that's something that we've just got to get prepared for, even though it's a year and a half away? Then one for Houman. You set out your enthusiasm for amlitelimab.
Lilly has just reported the findings from the Phase III ADJOIN extension study for Edglis, which looked at Q8 week dosing and showed very limited erosion in efficacy. I'd be very interested if you think that limits the differentiation for amlitelimab where you were aiming for your 12-week to be differentiated. Thank you.
Paul Hudson (CEO)
Okay, thank you. François, you want to catch that? Maybe Brian and Houman, depending. Yep.
François-Xavier Roger (CFO)
Yes, Matthew, I think that this is a good question for 2027 indeed, and which is what I presented in the last call at the end of July. The fact that in 2026, we will have, we will lose about EUR 300 million of R&D reimbursement from Regeneron. As I said a few minutes ago, it will be entirely offset by the additional royalties that we will receive from Amvuttra. In 2027, indeed, we will have a much more significant amount of R&D reimbursement in terms of decrease because we will lose EUR 800 million from one year to the other. This will not be fully offset in 2027 by the additional Amvuttra royalties, which will be around EUR 300 million, which is in one of my appendices in this presentation as well. We will have a gap indeed of about EUR 500 million.
Will we be able to cover it with other exceptional items or, let's say, non-recurring items? The answer is no. That being said, I mean, we will continue growing at a reasonable pace as well. I said it last time that if there was one year where we were not sure about increasing our profitability and deliver this profitable growth, it would be 2027 for that same reason. That being said, and I repeat what I said last quarter, which is we expect our BOI to increase in absolute value in 2027 in spite of this impact. We will be able in absolute value to cover the gap, the EUR 500 million gap. Most probably, I believe that we may be in a position, still early to say, to even increase our profitability in terms of BOI in 2027 as well. I say we may be, still very early.
We have not even completed our 2026 budget, so I want to be careful. Directionally, there is probably a possibility, largely as a consequence of the growth leverage that we will get from superior growth.
Paul Hudson (CEO)
Okay, thank you. Maybe Brian first and then Houman.
Brian Foard (Head of General Medicines)
Yeah, I think that's a great question. Thank you very much. I think as you look at the marketplace, we've always said this is a marketplace that's going to continue to grow. The biopenetration rate is extremely low, just over 14%. More assets coming into the marketplace will only help the marketplace grow. As you can see from our growth today in Dupixent, a product that's already on the marketplace, it's benefiting from other therapies coming to the marketplace. That said, one thing that we've said consistently for a very long time, these IL-13s are incomplete therapies, and we've seen them on the market now. Actually, if you look at LEVRI that's been on the market for nearly a year now, it has single-digit share. We're seeing while it's helping grow the marketplace, it's really not taking very much share from Dupixent.
Dupixent, we believe, still has a very strong profile. Each of these still have these dosing ranges that are either two weeks or at the best four weeks is what we're seeing right now. We think that there's a lot of room for a much more durable dose in the marketplace, assuming we finish the regulatory trials and get it to the marketplace for NEMA or for, excuse me, for.
Paul Hudson (CEO)
Houman, nope.
Houman Ashrafian (Head of R&D)
Just Matthew, thanks for the question, as well as the BioPen comment, which is important. This is a totally novel mechanism, an apical node in the immune response with not only durability, but multiple differentiating factors. We remain, based on the data, actually, for the case one study, encouraged by the potential for amla.
Paul Hudson (CEO)
Great, thank you. Next question.
Operator (participant)
Yes, next question from Seamus Fernandez from Guggenheim. Seamus.
Seamus Fernandez (Analyst)
Thanks very much. Just a couple of quick questions. Can you update us on riliprubart and the timing dynamics around that? It's unclear if that's still on track for second half 2026 readout in CIDP. I just wanted to clarify that. More broadly, just hoping to get a better understanding of when we're going to learn more about the programs that have had unfortunate outcomes and where a number of programs are under review, including the oral TNF, including itepekimab. It seems like there's a lot of secondary analysis exploration going on and holding on to assets as part of the pipeline. I'm just trying to get a better understanding of when we're going to know the advancement or elimination of some of those assets that haven't quite lived up to at least investor expectations. Thanks.
Paul Hudson (CEO)
Okay. Houman?
Houman Ashrafian (Head of R&D)
Thanks, Seamus. I'll try and be succinct on this one. On riliprubart, we've updated the timelines at this Q3. The reality is that the outcome for the two Phase III studies for CIDP are just creeping over the year. This is purely a patient recruitment phenomenon, and we look forward to seeing the results of those studies. You'll remember the phase two studies were extremely encouraging. On your second point about when you'll see the data and when we'll make decisions, obviously those data sets will all be presented at the relevant scientific congresses. I've already announced today that we will go forward subject to regulatory approval with our partners in etopicumab, so there's no tardiness there. Obviously, we have to take a regulatory opinion before we move forward into replication Phase III.
For the other studies, I've already alluded to the fact that we will take a portfolio view on asthma with a number of our assets and figure out what we take forward in asthma. On balinatunfib, we've just had access to the results. I've outlined the importance of ACR50 and 70 and the fact that they're clinically meaningful. We'll figure out, as we've always said, we've been consistent in our view that we'll figure out exactly the role of brevecamig in mono and combination therapies, both with our own molecules and partners.
Paul Hudson (CEO)
Thank you, Houman. Thank you, Seamus. Great questions. You know, we find it, we've seen it with many of our competitors having hits and misses in immunology over the last months that these extra levels of thinking actually are worth doing and standing in good stead because you really do pick the right patient population. Taking time, I think, is wise for us. Next question.
Operator (participant)
Yes, next question from Simon Baker from Redburn. Simon?
Simon Baker (Analyst)
Thank you for taking my questions too, please. Firstly, on Dupixent, François, you said that the gross margin benefit from manufacturing improvements is now fully being captured. I just wonder if you could give us some idea of the magnitude of the gross margin improvement this quarter, which is down to Dupixent manufacturing. A question on indication opportunities. Houman, you mentioned rosibutinib in Graves' disease. That's potentially not a particularly rare condition. I just want to get your thoughts on the potential you see there. Also, the other one in light of Moderna's failure this week is CMV vaccination. I know you've been in this space in the 1990s. I just wonder what your level of appetite was for it now. Thanks so much.
Paul Hudson (CEO)
All right, thank you, Simon. François.
François-Xavier Roger (CFO)
Yes, Simon. On Dupixent, the gross margin contribution from the C3 manufacturing was actually very limited in Q3 itself. I mean, this is, we just took the opportunity to mention that we have completed the full implementation of this new technique, which has spread over a couple of years, actually. It did not have a significant impact in Q3 per se. I take the opportunity to mention that our gross margin increased globally for the company by 2.5% in Q3 and by 1.8% in H1. Most of the factors contributing to it are still relevant for the future to a certain extent. One of them is volume growth. Our volume grew by 12% since the beginning of the year. We expect to continue at a high level. We are obviously benefiting from a positive product mix, including this quarter.
Ayvakit, actually, Ayvakit is much more significant than the new manufacturing technique for Dupixent. We are also obviously benefiting from the industrial restructuring that we did over the last couple of years. Plus, there were some one-offs this quarter, last year and this year, which did create a little bit of positive impact as well. If we look at it underlying, because we were at a high range, once again with 2.5% of increase in Q3, if we exclude the one-offs on some of the items that will not necessarily replicate each and every single quarter, like Ayvakit, for example, you can consider that the underlying gross margin increase that we have experienced since the beginning of the year is around 1%.
Simon Baker (Analyst)
Thank you.
François-Xavier Roger (CFO)
It is obviously before any impact. If you want to use that for the future, that does not include any potential impact coming from tariffs.
Simon Baker (Analyst)
You don't?
Paul Hudson (CEO)
Thank you, François. Okay, Houman, Graves, and then Thomas, CMV.
Houman Ashrafian (Head of R&D)
Okay, sorry, thanks for that insightful question. As you'll know, Graves is a well-established autoantibody-related disorder. The classic long-acting thyroid-stimulating antibodies, the TSHR antibodies, are important. Number one, it's a canonical autoimmune disorder. Number two, we know from investigator-initiated studies that B-Cell suppression is a successful therapy, particularly for the ophthalmopathy. Thirdly, with our unique covalent reversible molecule in rosibutinib that has already shown significant promise in multiple disorders, including Weiher IgG4 disease and ITP, I think that Graves is a promising opportunity. We look forward to taking the molecule forward. You are completely correct that it's not a rare disorder of that sort per se. It's not super rare. Therefore, I think it's a potential opportunity, particularly the ophthalmopathy.
Paul Hudson (CEO)
Thank you. Thomas, CMV.
Thomas Triomphe (Head of Vaccines)
CMV, I'll be short. Not much to say. The news is very recent, as you know very well, Simon. I will not comment on anything to see the full data set. The only thing I can refer to is indeed, you know, about quite a while ago, a few decades ago, we had worked on this antigen. It's a difficult target. While we had reached some, I would say, interim efficacy, our assumption at that time was that it would not be sufficient to reach a protection level. That's why we had interrupted this program quite a while ago. Sadly, overall, because the field of CMV vaccination is an important field, we would welcome a vaccine against this devastating disease.
Paul Hudson (CEO)
Okay, thank you. Next question, please.
Operator (participant)
Next question from Richard Vosser from JPMorgan. Richard.
Richard Vosser (Analyst)
Hi, thanks for taking my question. Question on Dupixent and just giving us a little bit more on the development around COPD and also the gross to net, how that developed in the quarter and how we should think about that in 2026, but also how the COPD launch is going, seems to be developing a little bit better this quarter. Second question, just on the inhibrics data. Just to file, I think you need some of the more long-term safety data that you called out from the open-label extension. Just wondering what, if anything, is being looked at in terms of that safety data from the regulators. Is there anything of interest that they want to see or rule out? Thanks very much.
Paul Hudson (CEO)
Okay, Brian, DP.
Brian Foard (Head of General Medicines)
Yeah, Richard, thank you so much for the question. First and foremost, I think the really strong overall growth that you've seen is really coming from all different sources of growth. If you think about it, first, our foundational indications, we continue to grow biopenetration in things like asthma, atopic dermatitis, EOE, nasal polyps. We moved into about a year ago, we launched in COPD, and we've really seen a strong success actually in COPD. One of our fastest, actually, it's our fastest respiratory indication as far as growth rate goes. That plus CSU plus BP, you can see now eight indications deep into the U.S. Our sources of growth are coming from everywhere and, of course, launching around the world. It also has actually created this really strong momentum we've seen with 26% growth this quarter and reaching over EUR 4 billion sales.
As it relates to gross to net, obviously that's captured in there in reference to our sales growth. This is something that we've monitored for a long time. We see that as we go into additional sources, if you will, there are different payer groups. We obviously will provide discounts to get into different access for different patient populations. This is something we've known for a long time, and it's captured in our long-term guidance for Dupixent.
Paul Hudson (CEO)
Okay, Houman and Hebrics.
Houman Ashrafian (Head of R&D)
Yeah, I'm excited to have done this acquisition, an example of our disciplined capital allocation policy. It's exciting that the preliminary data has proved so promising, superior both at Q3 and Q4 to some of the standards of care. You're correct that we're interested in the long-term extension study, which is open-label for the safety data. There is no specific, if you remember, this is a fusion protein-like antibody. There's no specific side effects we are looking for. You'll have noted from the press release that the safety and tolerability were in line with that, which was expected.
Paul Hudson (CEO)
Okay, thank you. Next question, please.
Operator (participant)
Next question from Michael Leuchten from Jefferies. Michael?
Michael Leuchten (Analyst)
Thank you very much. Two questions for François, please. One, I just wondered if I could prod you a little bit more on the seasonality comment on gross margin. You said the Dupixent process is now tucked in and you return to normal patterns. Just wondered what you meant by that. If most of the driver of the gross margin increase in Q3 still hold, just wondering why you opted not to offer an increase to guidance for this year. Thank you. Okay, thank you, François.
François-Xavier Roger (CFO)
Okay, Michael. As I said, the 2.5 percentage point increase that we had in our gross margin in Q3 is probably not necessarily a good proxy for 2026. I do believe that we have some factors that will stay there, like our volume growth, like, for example, even the product mix. These issues are structural, but we won't get another increase next year of 2.5 percentage points in gross margin. It will be probably closer, maybe to what I said, underlying maybe 1 percentage point benefiting from volume and product mix. The other thing in terms of guidance, I'm glad you asked the question. We do confirm our full-year guidance, which is high single-digit sales growth. Today, after nine months, we are at 8.8% year-to-date. Expect some increase from where we are at the end of September.
Business EPS growth is low double digit, even excluding the benefit of share buyback. We are excluding share buyback at 9.9%. Expect there as well for the full year that we will go up from where we are as at the end of September. Just to clarify as well, our full-year guidance assumes basically that Q4 will be the best quarter in sales, BOI, and EPS growth this year. We will do better than we have done in any of the quarters. Q3 was a bit softer because of the comps, as we said earlier. There is just one thing I want to take the opportunity to mention. One thing, maybe what the street does not always estimate is the profit sharing with Regeneron. That includes, by the way, both Dupixent and Kevzara, because there is probably an understanding that it grows in line with sales of Dupixent. It doesn't.
Let me just give you some further color. For example, if we look at Dupixent sales in H1, they grew by 21%, and the Regeneron profit sharing grew by 32%. So 11 percentage points faster. If I do the same analysis for Q3, Dupixent sales grew by 26%, which is remarkable, and the profit sharing with Regeneron grew by 37%. So another 11 points higher than sales. Once again, it is a profit sharing. It's not linked necessarily fully to sales, and there is about 10-11 points of growth in terms of difference between the two concepts.
Paul Hudson (CEO)
Thank you. Next question, please.
Operator (participant)
Yes, next question from Florent Cespedes from Bernstein.
Florent Cespedes (Analyst)
Good afternoon. Good afternoon. Can you hear me?
Paul Hudson (CEO)
Yeah.
Florent Cespedes (Analyst)
Yeah, thank you very much for taking my questions. Florent Cespedes from Bernstein. Two quick questions, please. First, on M&A, with the massive success of Dupixent and with the mixed-use flow pipeline, maybe could it be more aggressive in terms of product acquisitions and maybe kind of Blueprint-like transactions is something that we should see in the future. A second quick question for Thomas on vaccines. Could you share with us how do you see the trend, notably in flu, with the vaccines fatigue that we observe across the world? Some color on this would be great. Thank you.
Paul Hudson (CEO)
Maybe I didn't quite catch perfectly the first question, but it was regarding M&A and should we be doing more and more Blueprint Medicines-like is what I think I heard. François, do you want to comment?
François-Xavier Roger (CFO)
Just a few words, maybe Paul, you can complete it. It's not really about being aggressive. It's about finding the relevant acquisitions. We have a space in our balance sheet. We said that we want to retain our AA rating. In order to get there, we could afford, once again, this is not necessarily what we want to do, but we could afford investing in BBN M&A currently, something like EUR 14 billion, EUR 15 billion and still retain our AA rating. Anyway, what we are looking for is to meet three criteria, basically: strategic fit, which is around our four therapeutic areas and possibly white spaces as well; second, scientific differentiation and relevance, and the first in class, best in class; and third, financial return as well, without any certainty. It's less a matter of amount or aggressiveness.
It's more about finding the right targets at the right time at the right price.
Paul Hudson (CEO)
Yeah, I think that's great. We've been really disciplined. You know, François, when he came in, actually went back and looked at all of our acquisitions and agreements to decide whether we allocated capital to his standard. I was somewhat relieved to find out that he did. There is a huge amount of discipline. I think, you know, you've just heard how Ayvakit's done in Q3. We're really, I think we're very good at it, but we have to be a little bit choosy about what we do. I think that's very reasonable. Okay, Thomas, vaccines.
Thomas Triomphe (Head of Vaccines)
Thanks, François, for the question on flu. A couple of points. First of all, it's early. We're still in October. Indeed, as you had in mind with your question, I think it's fair with the first few weeks that we observe a little bit vaccination rate on the soft side when it comes to flu vaccination, particularly in the U.S. We see a soft VCR today. A couple of points, though, I'd like to highlight when it comes to the 2025 performance that you see in this quarter. First of all, we had highlighted it before, but I just want to be clear that it's linked to two elements. In Germany, there is a price effect where there is a significant price decrease due to the change of recommendation. In the U.S., it's more what you're mentioning, i.e., the soft VCR.
In both cases, in this 2025 environment, we are keeping a very strong market share performance overall for Sanofi flu vaccines, in particular, even for differentiated flu vaccines. Beyond the performance in terms of market share, what I'd like to highlight also this quarter in terms of flu is the progress we're also making on an R&D perspective. You see that we have a positive Phase III in Fluzone HD Efluelda 50+ extension. With the great performance you've seen with the fluidity trial and the fantastic 32% improvement compared to standard dose and fluidization, if we can extend that to people above 50 years of age, that would be fantastic. To be associated also with the progress we've made on pandemic flu, with what I think are best in class H5 seroprotection results and the move and progress we're making on flu-COVID combinations. Flu remains important for us.
We're moving forward full steam commercially and R&D-wise.
Paul Hudson (CEO)
Okay, thank you. Next question, please.
Operator (participant)
Yes, next question from David Risinger from Leerink. David?
David Risinger (Analyst)
Yes, thanks very much. Congratulations on the positive inhibrics elevate results this week. Could you provide some more color on how you would characterize for AATD, both the normal range and the trough levels? Regarding net price prospects for U.S. Dupixent in 2026, since your contracting is likely largely complete at this time of the year, how would you characterize the expected net change in pricing in 2026 versus the net change in pricing in 2025? Thanks very much.
Paul Hudson (CEO)
Okay, thank you. EBRICS, AATD?
Houman Ashrafian (Head of R&D)
Yeah, without running into any market issues, you'll remember that the definition of alpha-1 antitrypsin levels is related to the wrong crystal nomogram. I'll speak in broad terms. Standard of care, by and large, doesn't get into the normal range for alpha-1 antitrypsin levels. Our Q3 and Q4 molecules provide very commendable alpha-1 antitrypsin nomogram levels, both for trough and mean dose.
Paul Hudson (CEO)
Thank you. Brian, I think a clever question from David trying to get at the rebates likely for 2026 over 2025. I'll let you answer that.
Brian Foard (Head of General Medicines)
Yeah, I think it's a great question, David. Thank you so much for asking it. As you know, we don't typically give guidance on the net price year over year. One thing I will say is you can see we've been incredibly disciplined over the years. We're now eight years into the launch of this asset, and it's been captured in our long-term guidance how we believe the net price will develop over time.
Paul Hudson (CEO)
Thank you. Next question, please.
Operator (participant)
Yes, next question from Sarita Kapila from Morgan Stanley.
Sarita Kapila (Analyst)
Hey, thanks for taking my questions. Just on amlodipine, how should we think about the upcoming readouts? Is there potential for the placebo arm in the COAST-2 trial to behave more normally, or should we think about it as a pure sister trial to COAST 1? Just on Esteri, beyond the no plateau in efficacy that we saw in COAST 1, what's underpinning the confidence that the long-term efficacy can improve with time? Thanks.
Paul Hudson (CEO)
Great questions. Okay, Houman.
Houman Ashrafian (Head of R&D)
Okay, so I'll take them one at a time. Thank you for the question. Firstly, on COAST 2, it's a precise replica sister study. There are some subtle differences in regional recruitment and execution, but essentially, it's a replica study. We anticipate and hope that we will get a replica of COAST 1. As you'll remember, also, you said correctly on Esteri, it's a slightly more nuanced study than has perhaps been observed, as well as being able to tell us about durability ultimately in a randomized way. It will also give us a sense of dose variation that we will do. You'll remember there are multiple dose-switching arms. The punchline on Esteri, which we'll get throughout next year, is not only will it tell you about durability, but it'll tell you about the relationship between dose and durability.
Those are going to be critical in terms of our understanding of the positioning of amlodipine. Thanks.
Paul Hudson (CEO)
Okay, thank you very much, Houman. Yeah, we'll see. We'll get the data. We'll see how competitive we are. I think from a commercial perspective, we're very enthusiastic, but we'll let the data read out. Okay, next question, please.
Operator (participant)
Next question from Steve Scala from TD Cowen. Steve?
Steve Scala (Analyst)
Thank you so much. Two questions. Yesterday, Roche said they were taking patients back from Altuvio. What is the nature of the patient that is being taken back? What does this mean for Altuvio's long-term growth outlook? The second question is, based on the subgroup data presented at ECTRMS and the language in today's press release, it seems that any tolibrutinib SPMS approval will be in subgroups. What subgroups are likely to be in the final label? What portion of the overall SPMS market will this represent? Thank you.
Paul Hudson (CEO)
Houman, why don't you deal with that last question because we better clarify that as soon as possible?
Houman Ashrafian (Head of R&D)
Yeah, just to be clear, I'm going to give you two facts. The SPMS population is about 170,000, and the DPMS population is 120,000. At no point have we entertained the notion of doing subgroups. The regulatory discussions are ongoing, and we don't participate in any further insight during those regulatory discussions.
Paul Hudson (CEO)
Thank you. Brian, Altuvio.
Brian Foard (Head of General Medicines)
Thanks, Steve, so much for the question. A couple of things. Altuvio saw another really strong quarter. It's becoming very clear to us. This is the number one switched asset. It's being switched to, we are the number one asset that's being switched to in the hemophilia marketplace in hemophilia A. We're still seeing, as we have shared before in the past, we've seen about two-thirds of our switches coming from competitors. Of that, still 10% is coming from Hemlibra. I can't really comment on what Roche shared, but what we are still seeing is 10% is coming directly from Hemlibra. We are the number one asset that is being switched to. Now, about 1/3 of our business is still coming from a Loctate, but you can see our overall, that's starting to stabilize, and our overall HEM-A business is actually growing quite significantly.
We're very pleased with the performance and remain committed to delivering our next blockbuster this year with Altuvio.
Paul Hudson (CEO)
Great, thank you. Next question, please.
Operator (participant)
Next question from James Quigley from Goldman Sachs. James?
James Quigley (Analyst)
Hello, thank you for taking my questions. I've got a follow-up question for François-Xavier Roger, on the antibody payaway. I think backing out how the BOI margin seems to have been developing for Dupixent. It looks like last year it was in the region of sort of 62%. This year, third quarter, it looks like it reached 72%. If we're working backwards, maybe there's like a 92%, 93% gross margin. First of all, is that the right ballpark in terms of what we should be thinking about when calculating the payaway? As you mentioned, it seems to not necessarily be fully reflected in consensus. Going from a 72% operating margin going forward, how should we think about operating leverage? Obviously, going from last year to this year, it looks like there was a big step up. You mentioned the increase in percentage points growth for the payaway relative to Dupixent.
Where could the margin go and how should we think about that going forward? Maybe more so, at what point could the margin peak? Secondly, maybe one for Brian as well, a follow-up on Altuvio. You mentioned about taking share from other factor VIII therapies. Where are you now in terms of the factor VIII market from a market penetration and market share perspective? Where do you think you're going to end up? If that's below 100%, given the data, why would that be the case?
Paul Hudson (CEO)
Okay, some highly specific questions. James, thank you. I think François, you'll just give a broad comment to that.
François-Xavier Roger (CFO)
James, I would like to help you, but we don't disclose the margin by products, and we don't do it for Dupixent or for any of our products. Unfortunately, I cannot provide you any information on that. Obviously, the margin has been improving for Dupixent over time, given that we are benefiting from scale efficiencies, as I said earlier. Our margin has continued to increase.
Paul Hudson (CEO)
Okay, thank you. Brian, maybe similarly, I don't know how specific you want to be on margin.
Brian Foard (Head of General Medicines)
Yeah, can't really get incredibly specific on that. I mean, what you see in the HemA marketplace is that you've got the factor marketplace, which is, again, as we said, where we continue to take the most business from is the factor marketplace. This is a factor therapy that obviously comes with increased efficacy. We are taking some from the non-factors, as I mentioned before, 10% coming from Hemlibra, but we don't know, we haven't shared exactly where that might end at the end of the day. As we said, we're the number one asset that is being switched to. The progress continues and we'll continue to keep you updated as it develops.
Paul Hudson (CEO)
Okay, thank you. The last question, I think.
Operator (participant)
Yes, last question from Peter Verdult from BNP Exane. Peter?
Peter Verdult (Analyst)
Yeah, hi there. Peter here from BNP. Given I'm the last on the call again, maybe I'll pepper Houman with a few quick pipeline questions. Just on itopicumab, Houman, is it simply a case of the go-forward strategy that you repeat the RFI trial or will you solely be looking at the former smokers only? On FDO, data looks great. You need to gather safe data, but just on the regulatory pathway, if I recall a few years ago, FDA was making some noise about wanting to see respiratory functional endpoints as well as the biomarker analysis. Is any of that going to be required for FDO? Lastly, on TOLI, SPMS opportunity huge. How concerned or not should we be about TOLI getting an onerous label requiring weekly liver monitoring? How much of an issue would that be in your mind commercially? Thank you.
Paul Hudson (CEO)
Okay, Peter, thank you. Last but not least. Okay, Houman.
Houman Ashrafian (Head of R&D)
Looking forward to seeing you next week. Firstly, to start. Second, let's get into it. R33, broadly speaking, we anticipate that we will have to do some form of replicatory trial. The details of exactly what we do have been guided by both internal and external data sets. We've looked broadly, trying to understand why RFI 1 and 2 differed. The exact construction of those trials will be dependent on both discussions with our beloved partner Regeneron, but also the regulator. Look forward to more on that soon. On FDO, or as we call it internally, DORA, just to be clear, you're right that the FDA, first FDA, may have different perspectives. You'll remember that current standard of care dates to a target of 11 micromolar, which is about 50% below the limit of normal of the range. Many patients drop way below that three to five days.
The first point I would make is, and we will disclose the data at a conference, the Q3 and Q4 W dosing that we have is substantially better than that. We will have a conversation with the regulator as to, A, their intrigue related to those levels, but also what other additional endpoints we'll need pursuant to both natural history data and our open-label extension safety data. On your third point, on TOLI SPMS, we're in late-stage discussions. As I said, the brief is 28th of December. While we anticipate that we'll need some sort of RAMs with TOLI, there's been no further disclosable comment on the intensity of blood draws.
Paul Hudson (CEO)
Maybe on that last point, Houman, it's fair to say, isn't it, that we learned a lot actually between RFI 1 and RFI 2. I think you touched on that. We'll go, if you like, even better informed. On TOLI, that first 90 days of what we did in the clinical trial program and what we're doing in real life seems to be very practical and responsible. I think we're confident we have the right approach. Of course, it's the regulator that will decide what that looks like.
Thank you, Peter. Thank you all. Our growth momentum continued in Q3. After three quarters of sales and earnings progress, we reiterated our 2025 guidance. Our pipeline delivered important milestones in this quarter, as outlined earlier. Finally, as we're looking forward to 2026, we are confident in our ability to pursue our current trajectory of profitable growth.
With this, I wish everyone a good autumn. We'll now close the call. Thank you.