Ladies and gentlemen, thank you for standing by. Welcome to the Sanofi fourth quarter 2020 earnings call and virtual capital markets day. We have planned for a 15-minute break between both events. You may remain connected to this Zoom link for all sessions. I would now like to turn the call over to Eva Schaefer-Jansen, Head of Sanofi Investor Relations. Please go ahead, Eva.
Good morning, good afternoon, and good evening to everyone. Thank you for joining us to review Sanofi's 2020 fourth quarter results, followed by a dedicated Q&A session. In about an hour, we will begin our virtual capital markets day presentation and discussion. As usual, you can find the slides to both sessions on the investors page of our website at sanofi.com. Moving to slide two, I would like to remind you that information presented in this call contain forward-looking statements that involve known and unknown risks, uncertainties, and other factors that may cause actual results to differ materially.
I refer you to our Form 20-F document on file with the SEC and also our Document d'Enregistrement Universel for a description of these risk factors. With that, please advance to slide 3. Our speakers for the earnings portion of the presentation today are Paul Hudson, Chief Executive Officer; the Global Business Heads, Bill Sibold, Thomas Triomphe, Olivier Charmeil and Julie Van Ongevalle; and Jean-Baptiste de Chatillon, Chief Financial Officer. Paul will make some introductory remarks, followed by our GBU Heads, who will review the fourth quarter performance of their respective businesses.
Jean-Baptiste will provide an overview on key financials and we will then open for dedicated Q4 earnings Q&A session. For the Q&A, you have two options to participate: option one, click the raise hand icon at the bottom of your screen. You will be notified when your line is open to ask your question. At that time, please make sure you unmute your microphone; or option two, submit your question by clicking the Q&A icon at the bottom of the screen. With that, i'd like to turn the call over to Paul.
Thank you, Eva, and welcome to everyone, and thank you for joining us today. Apparently, a record number of joiners, so obviously creating a lot of interest in the story and how we're doing.
13 months following the announcement of our Play to Win strategy, and in the year of a global pandemic, we're delivering 3.3% sales growth in constant currency, ahead of the 2.8% growth the year before. I'm extremely proud of our achievements. Dupixent has become Sanofi's number one product in 2020, reaching EUR 3.5 billion in sales and at a growth rate of 74%. Our influenza vaccine franchise crossed the EUR 2 billion mark, responding to the public health needs with our differentiated flu products. Specialty care grew strongly during 2020, and despite fewer new patient starts due to the COVID environment. General medicine sales in 2020 were lower, reflecting the implementation of the VBP in China, though we've made progress on volume, and then further impacted by elective procedure delays, especially during Q2.
Our bottom line grew faster than our top line as we continue to identify efficiencies and reallocate spending to our key growth drivers. Across the sector, we saw companies lowering their spending throughout the pandemic. The difference is that we are implementing a disciplined active program of overall cost reduction and reallocation that will remain after COVID. As JB will explain, we have already achieved approximately 85% of our 2022 savings target in just one year and feel confident to increase our target overall. This year has proven that we have resilient, yet attractive businesses that set us up well for continued growth. I'm really confident that we will emerge stronger from this continuing crisis. Slide five. Transitioning now to Q4 performance, we delivered a tremendous quarter. Sales grew 4.2%, while business EPS grew 9.8%, which bodes very well for 2021 overall.
Key growth drivers were Dupixent, 54% up compared to the same quarter last year, and our differentiated vaccine business, which grew 15% with flu sales up 25% in the quarter. To achieve a nearly double-digit EPS growth, we delivered another quarter of P&L leverage, supported by further efficiencies and reallocating spending to growth drivers. With that, I'm now turning it over to the GBU heads. To provide more details on their respective businesses, let's first start with Dupixent and Bill, over to you.
Thank you, Paul. Starting with Dupixent, sales reached EUR 3.5 billion for the year, a growth of EUR 1.5 billion over 2019. Strong sales momentum continued into Q4, with sales of EUR 982 million, reflecting outstanding performance both in the U.S. and ex-U.S. across all three approved indications. This was all done in the backdrop of the second wave of COVID-19. In the U.S., patient visits continued to be approximately 80% of pre-COVID levels, and outside the U.S., local lockdowns prevented many patients from visiting their doctors. Other highlights in the quarter included Dupixent's listing on the China NRDL just five months after launch, one year earlier than the initial best-case scenario, enlarging the accessible adult population with atopic dermatitis to at least 150,000 as of March, a number almost as large as the roughly 230,000 patients treated with Dupixent worldwide today.
The opportunity in China may grow to around 900,000 patients over time for adult AD alone. In Europe, Dupixent is now approved for children six to 11 years of age with severe atopic dermatitis. Dupixent is the first and only biologic medicine approved in the pediatric patient population. Based on the continued successful launch execution, we are more than ever before convinced in our greater than EUR 10 billion peak ambition. On slide seven, I would like to share with you some insights that further exemplify Dupixent's uniqueness. Dupixent steadily increased sales quarter after quarter in the U.S. during 2020, but that wasn't true for every other dermatology biologic over the past four quarters. What set Dupixent apart in 2020 was the commercial execution and its product profile. As we move into 2021, we are even more confident in Dupixent's market leadership.
Recent top-line data readouts from potential future entries in dermatology and respiratory have not changed our confidence in Dupixent's position as the first-choice systemic therapy, based on its clinical profile balancing rapid and sustained efficacy with long-term safety. On slide eight, looking across our specialty care franchises, sales grew strongly by 18% in the fourth quarter. Besides Dupixent, oncology sales grew strongly, driven by the newly launched products SARCLISA and Libtayo. Rare blood disorder growth was higher than prior quarters as sales of Alprolix and Eloctate to our collaboration partner, Sobi, were higher than usual due to a change in the supply agreement. In multiple sclerosis, Aubagio's growth slowed to 4% globally and was flat in the U.S. following the entry of competition. With around EUR 2 billion in annual sales, Aubagio probably reached its peak in 2020.
With that, I'll hand it over to Thomas to update you on the vaccines business.
Thank you, Bill. Q4 2020 delivered a strong quarter of growth in the mid-teens, driven by higher influenza sales. Before we dive further into the flu franchise performance, I would like to highlight the continuous strong performance across our pediatric combination vaccines portfolio, growing by 20%. Main driver was Hexaxim, our hexavalent pediatric vaccine, especially in the rest of the world area, helped by favorable phasing of our polio vaccines. Importantly, our meningitis franchise returned to growth in the quarter, driven by catch-up in the U.S. following COVID-19-related delays earlier in 2020. Finally, as expected, the pandemic continued to weigh on our travel and adult booster vaccines.
For the full year, you have seen that we grew 9% in 2020, the second year in a row of high single-digit growth at the upper end of our mid to high single-digit growth outlook announced at Capital Market Days in December 2019. Next slide. Here you can see, focusing on flu vaccines, as already mentioned by Paul earlier, our flu franchise exceeded the EUR 2 billion mark for the first time ever, an increase of 38% compared to 2019. There are three main reasons for that. First, we responded to an increased demand and shipped more than 250 million doses worldwide, up over 20%. Second, we benefited from an acceleration of vaccination rates as a result of the pandemic, especially in Europe. Third, we continue to execute on our strategy to shift our portfolio to differentiated vaccines that offer a higher degree of protection for the most vulnerable people.
Differentiated vaccines accounted for nearly half of our global flu sales in 2020, up from around 35% only four years ago. Our successful differentiated products in the U.S., Fluzone High-Dose and Flublok, are now available in Europe under the brand names of Efluelda and Supemtek respectively. We therefore remain confident on the future growth prospect of our flu franchise. Our differentiated products currently set the standard in terms of efficacy, and they are expected to remain a significant growth driver in the coming years, with broader availability outside of the United States of America. Finally, let me use this opportunity to say a few words on the mRNA technology, which seems to work really well on COVID-19 and could also be applicable for flu.
Having said that, clinical data in seasonal influenza still have to be generated and will have to surpass the efficacy as well as the strong safety benchmark set by our influenza-differentiated vaccines. We are now getting ready to start a phase I trial of an mRNA flu vaccine this year as part of our collaboration with Translate Bio. Regardless of high-dose, recombinant protein, mRNA, or a combination of those platforms, we do intend to remain the leading provider of flu vaccines worldwide, protecting people all around the globe. With that, I hand over to Olivier.
Thank you, Thomas. As expected, our general medicine China business returned to growth in the fourth quarter, growing at 4%, with strong volume gains from Plavix and CoAprovel, up 78% for the year. This strong trend confirms our successful VBP bidding strategy, which delivered as planned. While the usual year-end true-up took place in the U.S. in Q4, we note that globally, the decline in the diabetes business saw significant moderation compared to previous years. This positive trend that we are seeing in our diabetes business is mainly driven by the growth of Toujeo in Europe and the rest of the world, as well as Soliqua uptake in all geographies. With the launch of Toujeo in China in Q4, we are confident in the outlook of the diabetes business in our key markets. I will elaborate on this in more detail at the CMD session.
In established products, we saw strong performance from Lovenox globally, benefiting from its continued inclusion in WHO guidelines for hospitalized COVID patients. Tail products of the EP portfolio in emerging markets face some headwinds from the COVID environment. Going forward, to improve the growth profile of the EP business, we continue with the portfolio streamlining, and we are making solid progress in driving simplicity and agility, such our go-to-market digital model. I look forward to sharing with you more on our strategic priorities for the General Medicines portfolio a little bit later today. With that, I hand the call over to Julie.
Thank you, Olivier. Similar to Olivier, I look forward to speaking with you again later today to share with you our team's strategic priorities to change the trajectory of our CHC business to grow our top line while continuously improving our bottom line. Let me now very briefly touch base on our fourth quarter performance of the CHC business. Following the annualization of Zantac, the U.S. returned to growth with strong performance from the allergy, digestive, and sleep categories. As a result, I'm happy to share we're back to gaining share in the U.S. OTC market since October. I would especially like to highlight the U.S. allergy category, which grew by 13% in Q4, with strong performance of our brands Allegra and Xyzal, both benefiting from strong 360 marketing programs, and Xyzal from product placement at a popular chain of U.S. membership-only clubs.
Globally, digestive health brands Essentiale and Dulcolax performed well as many consumers adapted to different lifestyles during the pandemic, including a more sedentary lifestyle at home. Outside the U.S., the cough and cold category was down 31%, driven by our high penetration in cough in Europe and an overall weak cough and cold season across regions because of social distancing, as well as lower pharmacy foot traffic. With that, I hand it over to our CFO, Jean-Baptiste.
Thank you, Julie. Paul mentioned in October that we are committed to fully embrace sustainability in our Play to Win strategy, and it's happening. It's happening across the company. As an example, the finance team linked the renewal of our EUR 8 billion revolving credit facility with some of our key targets. We had seen many green bonds in the past, but this one was a first with an ESG revolving credit facility. You will see over time many other proof points across the company. On slide 14, let's turn to financial performance. Company sales increased 4.2% in the fourth quarter, an acceleration versus previous quarters. We delivered another quarter of P&L leverage driven by further efficiencies. Within the lower R&D spend, you have already a higher spend on the specialty care franchise due to the reallocation from diabetes on cardiovascular.
These operating expense efficiencies more than offset a decline of 120 basis points in gross margin due to U.S. diabetes drop on product mix of the General Medicines business. Consequently, BOI grew almost 10% and our BOI margin increased by 60 basis points to 21.9% in the quarter. We have been able to deliver this margin improvement at the same time as accelerating investment in Dupixent and vaccines, and absorbing the Synthorx and Principia R&D spend. On slide 15, full year 2020 P&L. Well, I would like to draw your attention to the last line on the slide. Our BOI margin increased 120 basis points to 27.1%, well on track toward our communicated BOI margin ambition of 30% by 2022. Going forward, you can expect operating expenses to grow again due to investments into our expanding pipeline and future launch activities.
At the same time, you can expect to see a gross margin improvement from this low point of 2020. With this in mind, let me give you an update on our progress to accelerate efficiencies. On slide 16, as you know, we communicated in December 2019 our plan to deliver EUR 2 billion in cost savings by 2022. Of this total, we expected around EUR 500 million to come from reduced spend in deprioritized businesses, around EUR 1 billion from a range of smart spending initiatives, and a further EUR 500 million from operational excellence, including COGS. In 2020, we have achieved around EUR 1.7 billion of savings, almost 85% of our 2022 target. We made progress across all potential sources of savings, especially from deprioritized businesses on operational excellence, where we have surpassed the target. Following these accomplishments, we are increasing our cost savings target by EUR 500 million -EUR 2.5 billion by 2022.
These savings will be derived from continued operational excellence. We plan to reinvest 100% of this extra EUR 500 million of savings to drive the top line and fund the pipeline. On slide 17, we delivered another year of strong free cash flow growth, mainly driven by Sanofi's solid business performance on smart spending initiatives. Free cash flow increased by more than 70% against full year 2018. We delivered a strong underlying performance. As a matter of principle, we do not update our midterm targets. I guess you will understand that concerning free cash flow, we will maximize it as much as we can. On slide 18, I want to transition to Sanofi's annual dividend payment, which the company has consistently grown for the last 26 years.
As a result of Sanofi's performance in 2020, we announced that the board has proposed a EUR 0.05 uplift in the dividend to EUR 3.20. A growing dividend remains an important element of our capital allocation policy, but ranks behind organic investment and business development, which are our main priorities. On my final slide, we have set out our full year guidance for 2021 business EPS to grow in the high single digits at constant exchange rate. On Forex, we see around 5% negative foreign currency impact based on January average exchange rates. Lastly, I want to highlight push and pulls for 2021. Well, on the upside, we expect strong growth from Dupixent and vaccines, and continued efficiency benefits to be reinvested in growth engines and pipeline. In addition, we will have the annualization of the China VBP impact from Plavix and CoAprovel.
Sanofi's tax rate for 2021 is now expected to trend towards 21%. This is our estimate, including the positive impact of the French taxation reform. Our current forecast does not include a potential change in U.S. tax legislation. On the downside, we expect the COVID environment to continue to impact us in H1, with potential gradual normalization in the second half of the year. In addition, we expect adverse impact of foreign currencies, primarily in the first half of the year, on continued U.S. diabetes price erosion. Taken together, these factors suggest that our growth will be weighted to the second half. In addition, you should note, but I'm sure you have it in mind, that the first quarter will face a high basis for comparisons, as Q1 2020 does not fully reflect current market dynamics due to the pandemic.
After 6.8% growth at CER in 2019, on 9.2% in 2020, we are on track for another year of a high single-digit growth. While you can look back on past performance, but definitely, this is not the same Sanofi. Let's open the call now to Q&A. Eva?
We will now open the call to your question. As a reminder, we would ask you to limit your questions to two each. As a reminder, you have two options. Option one, click the raise hand icon at the bottom of your screen. You will be notified when your line is open to ask your question. At that time, please make sure you unmute your microphone. Or Option two, submit your question by clicking the Q&A icon at the bottom of the screen, and I have seen some have already started. Your question will be read out by our panelists. Now we will take the first question from Pete Verdult at Citi. Pete, please go ahead.
Yeah, thank you very much. Pete Verdult, Citi. Two questions, maybe kicking off with Thomas first on vaccines. Just could you comment on where vaccination rates ended up this past winter in Europe and the U.S.? Although you've given us a split by value, could you just remind us perhaps from a volume perspective, the mix between your differentiated and commodity flu business? Then secondly, for John, on upcoming SERD data. Is the data in-house yet? Can you remind us whether we will see PFS as well as ORR data? Should we be using the PALOMA-3 and MONARCH 2 data as the benchmarks when we assess the SERD data? Thank you.
Okay, Pete. Thank you. Thomas, over to you.
Thank you, Pete. In regards to the vaccination coverage rates, we don't yet have final numbers because this is still ongoing by every single country in terms of North America or Europe. It's clear to say that due to the COVID-19 pandemic, we've seen some increase in the VCR. I would expect roughly an increase of the U.S. market by around 14%, one four. Again, that's not final numbers. It's with some interim IQVIA data. In Europe, we've seen a significant increase on the vaccination coverage rate. Also a few points, but we'll know more in the next couple of months once we have the final numbers.
When it's come to value and volume split, on the overall flu business, if I look at 2020, you've seen that roughly it's a balance between volume and value in terms of the 38% increase in the flu business. Of course, as mentioned, we're going to increase further the differentiated flu portfolio. We are very happy as we've seen the introduction of Efluelda in Europe. We believe it will be a strong driver of growth in Europe in 2021 and the years after. I will say that we'll see more and more increase of the differentiated flu in both volume and in value in next year.
Thank you, Thomas. John Reed, maybe you could update on what data we have in-house, and the outlook for sharing data on our SERD arm, amcenestrant.
Absolutely. Thanks, Paul. We'll be sharing data on the phase I-B study, which set the stage for the pivotal study in combination with palbociclib that'll be shared at a medical conference middle of this year. In terms of the first pivotal readout, that will occur the first half of this year in the second and third line setting as a monotherapy. That primary endpoint is progression-free survival. Of course, we'll have overall response rates and clinical benefit rates as well as secondary endpoints, but PFS will be the primary endpoint.
Thanks, John.
The next question is from Wimal Kapadia at Bernstein. Wimal, please go ahead.
Oh, great. Thank you very much for taking my questions. Wimal Kapadia from Bernstein. Can I just ask on venglustat, please? Clearly disappointing to see the update on GBA-PD, but given safety continued to be favorable and the biomarker showed consistent and predictable GL-1 reductions in both the plasma and cerebrospinal fluid, have your views of success actually changed for the product in ADPKD for the pivotal data in 2022? Just tied to that, should we still be expecting kidney volume data this year, which may be fileable with FDA depending on the outcomes? My second question is again back to influenza. Clearly a strong 4Q and stronger than the 3Q, which was above your previous comments. I guess can I just ask what drove that stronger-than-3Q performance? Secondly, how should we think about the flu progress in 2021?
Do you expect patients who took a vaccine this year that typically do not to fall off in 2021, should the pandemic be in a better position, or do you expect incremental demand in 2021? Thank you.
Thanks, Vimal. I'll come to venglustat in a moment. I'll make a comment before John, but maybe let's just do flu while we have a chance. Q4 over Q3, and also outlook for 2021.
Q4 versus Q3, it's related to the three drivers we've mentioned before. Clearly, COVID-19 has shown an increase of influenza rate in 2020, and therefore, there was an expansion, I would say, of the season and hence the balance between Q4 and Q3. Moving forward, we expect to see Q3 and Q4 roughly 50/50% balanced. Of course, there are many different factors influencing that. For example, what will be the new strains, when they are announced, what's the impact? As we get more data points, we'll be able to give you some more guidelines on that in the coming quarter. When it comes to 2021 outlook, what we've observed in the past is a slight decrease in VCR post-pandemic situation. There might be a couple of points down next year in terms of overall influenza VCR.
What's very, very important and very specific to the Sanofi Pasteur portfolio of influenza vaccines is that it's the growth of our differentiated flu vaccines. Which come with a premium in terms of efficacy, but also a premium in terms of pricing. I think that from a value perspective, we'll be able to be well-positioned to deliver on our mid to a single-digit growth ambition that we have for the GBU, and influenza will be a part of that.
Thanks, Thomas. John, we'll come to you on venglustat, maybe we are going to go through it in a little bit more detail later at Capital Markets Day. I think, Wimal, your summary, if you like, was spot on. At least how I felt when I saw the data, it's one of those sort of paradoxical moments where although we were disappointed in Parkinson's for those that are struggling, we increased our confidence outside of that. Maybe I'll let John answer.
Thanks for the question. Just to get to the question that you asked about the total kidney volume and when we'll have those data, that will be next year. That's when we'll have that readout. In terms of the mechanistic hypothesis that we're testing, it is different from the Parkinson's situation in the context of the autosomal dominant polycystic kidney disease. The glycosphingolipids that are being impacted through the modulation of that pathway are acting like signal transduction molecules that affect differentiation of the kidney cells. It really is a different mechanistic hypothesis, really an independent hypothesis, compared to what we tested in Parkinson's.
Great. Thank you very much.
Okay, John, I think we'll leave it because we'll cover it a little bit more later, the read across, but I think you got to the nub of it. Next question.
The next question is from Jo Walton at Credit Suisse. Jo? Jo, please make sure you unmute your phone. Okay, let's move to Graham Parry at Bank of America Merrill Lynch. Graham?
Great, thanks. Can you hear me?
Yeah.
Okay, perfect. Just going back to vaccines again, I'm afraid. Could you just help us understand what growth in vaccines is assumed in guidance and in particular for flu? I think, Thomas, did you say that growth would be a couple of points down on 2020, but you're still expecting to see flu grow off that two and a half billion base? What sort of recovery and cadence of recovery are you expecting in travel, meningitis, and boosters? Presumably, that's all sort of second half loaded. Secondly, on Dupixent, obviously accelerating growth in fourth quarter on prescriptions, can you just help us understand what's happening on pricing as you go into this year? Has there been any pressure from payers at all, or are you still enjoying pretty good coverage without too much pressure there? Third question is just on other operating income.
That was around EUR 100 million lower, or the expense I should say, was about EUR 100 million lower than consensus. You actually had quite a high Regeneron payaway in there. Are there some low-level one-off gains sitting in there? If you could just help us understand the size of those. Thank you.
Okay. Well, we'll start with Thomas. I would just add that I think we would all believe as much as we'd love to be back traveling again, the more exotic travel perhaps will be much later in the year and perhaps the beginning of the following year. Thomas, I'll leave it to you.
Thank you. Hi, Graham. What I was saying is that, and it's important to be precise, the overall vaccines GBU growth is expected into the mid to high single digit trajectory as we've committed from 2020 to 2025. When I was mentioning -2%-3%, it's on the vaccination coverage rate for the full market, so not about Sanofi Pasteur. When it comes to us, we expect influenza to remain a key growth driver of our overall trajectory next year and the years after. Again, it's about a few factors. You understood the importance of Efluelda, i.e., flu and high-dose growth in Europe and still in North America. That's very important. We expect also Flublok growth to keep going. What's also important for you to know is that you know that we will keep investing in our capacity.
Notably, in 2021, we'll have the start of our new U.S. facility for flu and antigen. That will start to produce from the year 2021. We've committed in the past, but of course, that's an important driver when it comes to flu and high-dose. Same thing, we had also invested into our Vaxigrip influenza vaccine in France, in order to make sure that we can meet the demand. That's very important moving forward for flu. In parallel, to sustain the mid to high single digit growth of the GBU, the recovery on meningitis, you've seen in the Q4 that meningitis was turning positive, and therefore, we expect this to come back in 2021. That's an important part of the driver. As mentioned by Paul, I expect travel and endemic to still be impacted in 2021 for the obvious reasons we know.
That's more a 2022 play in our view. You've also seen, and I highlighted at the beginning of the call, that our pediatric combinations have done well this year like the previous year, and we think that in emerging markets, they will keep their growth trajectory in 2021.
Thanks, Thomas. Bill, maybe you want to jump in on Dupixent access quarter one and onwards, what you see as the dynamics?
Thanks, Graham. First of all, we're in a really highly favorable access position. We have greater than 95% of commercial lives having established UM criteria for AD and asthma. As we launched the product, we knew a couple things. We knew that we'd be in multiple indications, and we knew that there would be competition in the future, because strategically approached this, and we've done very well. Looking ahead to Q1, you would expect, like in every other Q1, you have a resetting of insurance, so your patient assistance programs and so forth have that impact. We believe we're in a really strong position. Clearly, when you have competition coming in, the more companies there are, you expect some impact on gross to net.
As I said, we started out with the plan knowing exactly how the market was going to unfold, and we think we're in a really favorable position for Q1 and 2021 in general.
Thank you. JB, BOI?
Yes, Graham. Yeah. You spot it perfectly. Effectively, we have an accumulation of small deals. We are very active on the front of divesting some of our molecules in IP portfolio, a bit in consumer health also. That's to execute on our commitment of the capital market day. We are effectively executing on it, almost computing to below EUR 100 million, but quite near on Q4. Cash-wise, it's much more important what we are doing. As you know, we are pushing down some goodwill, accounting-wise, when we account for those sales. It's not really impacting on BOI, but Q4 was higher.
Okay. Thank you. Next question.
I have on the chat two questions from Florent Cespedes from Société Générale. The first one is on 2021 R&D news flow, specifically with regards to BIVV001 and fitusiran and what the new timelines are. The second one is could you be more specific in where you intend to redeploy the EUR 500 million additional savings?
Okay. Well, John, maybe you want to update on BIVV001 and fitusiran for this year. It was a more broad question about news flow for 2021. Yeah. John.
Yes. Thanks, Paul. BIVV001, which is now known as efanesoctocog alfa, the study is fully enrolled. Last patient has been enrolled. It's a 52-week study, that'll be reading out early in the following year. We're slightly delayed due to COVID, are still expecting to have a submission in roughly the same timeframe that we've disclosed previously. With fitusiran, after the voluntary hold to reconsider dose and schedule, the study has now been restarted. 97% of patients remained on study. The investigators and patients were very eager to resume, we're delighted that we were able to get back on track with that study. We'll be having dialogue throughout the first part of this year with the health authorities in terms of what additional evidence they'll want to see in order to submit the NDA.
We don't yet have an update for you on the timing for the fitusiran final submission.
John, broader news flow for 2021?
Well, for 2021, we will have eight pivotal readouts. That will include amcenestrant in the first half of the year for the monotherapy and the second, third-line breast cancer, as well as two Libtayo readouts.
In the second half of this year, we'll have two Dupixent readouts for spontaneous urticaria, chronic spontaneous urticaria, as well as for prurigo nodularis, two more dermatology indications. We'll also have rilzabrutinib pivotal data for pemphigus vulgaris, another dermatology indication. We'll have a readout for SARCLISA in the frontline myeloma context for the transplant-ineligible population. Expect a rich year of news flow throughout 2021.
Thanks, John. Maybe just to add, and we maybe will talk about a little bit later, but the investigative feedback on fitusiran, I know everybody was disappointed that we'd be on a voluntary hold, but actually it's provided us with some much richer insights into the potentials for interval and dosing, which while nobody wants to take a short delay, actually, we think the profile may improve. We will see. We'll see what the data says. We wouldn't have found this out, I think, unless we'd been on this journey. Okay. Next question?
Another question from Geoff Borges. What proportion of your volume now is in the U.S. and globally is in premium brands? This is for influenza vaccines. It's a volume question on split U.S., ex-U.S. The second part is, are you underway with a combined flu COVID vaccine, and do you believe COVID will become another repeated new vaccine annually?
Thomas, just before you answer those great questions, I did neglect to throw the question to JB on the reallocation into R&D.
Oh, yes. Thank you. I think it's an important question to read through what happened already in 2020. It was a very significant swing. It was EUR 500 million savings in 2020 from effectively arbitrage within our portfolio. It was happening very quickly, and you see it on my slides about savings. That's why in 2020 already, we saw an acceleration of the spend of R&D in specialty care, and that's where we are, of course, investing. Efficiencies also have helped accelerating this level of spend in R&D in specialty care. You were asking of the EUR 500 million, the next EUR 500 million. Yes, a lot of them will come this time from COGS, which will of course tie up with the improvement we are expecting on the gross margin. Yes, we are looking at reinvesting them because we are gaining confidence on our top-line growth.
It makes us much more confident that we can reinvest it behind our pipeline, which is of course more and more promising. We need to invest into it. You remember that with Synthorx, Principia, Kiadis, Kymab, all those companies we have acquired, we will have the annualizing of their cost in 2021. You can expect to see effectively R&D spend going up, but in a completely different context than before. Instead of being spread all over the place, it's really connected to our priorities in specialty care and in vaccines. I hope it gives more color to what we are executing.
Thanks, JB. Thomas?
Back first to influenza, and then I'll talk about COVID-19. For influenza, again, I think what's important to have in mind is that with the new flu and antigen building coming online in 2021, you should expect a growth of both our differentiated vaccines, i.e., Fluzone High-Dose Fluad and Flublok Supemtek. I do expect a growth on both sides of the pond in North America and in Europe, especially for, again, Fluad, Fluzone High-Dose. You will see that in North America, you will see that in Germany. I expect maybe a significant growth in volume and in value from the differentiated group. What will be the impact on the standard dose flu remains to be seen. That's more linked to the vaccination coverage rate, as we discussed before. When it comes to COVID-19 and influenza, great question.
A little bit too early to have a definitive answer. There are still many things in terms of ability to do COVID-19 and flu together. You know very well that flu has a very specific logistic, that it's an annual vaccination. We still need to see what's going to be the need for boosting, by when, and how long are the COVID-19 shots' duration. Many questions to answer there. You have noticed that we are very interested. You have noticed that we are starting phase I of mRNA flu vaccine this year. Knowing that we are the influenza vaccine leader worldwide, and knowing that we have two shots on goal with COVID-19, should there be an opportunity, we'll be just around the corner.
Thank you, Thomas. Next question, please.
The next question is from Jo Walton. Jo, please go ahead. No. Okay, let's move on to Richard Vosser at JPMorgan. Richard?
Hi. Thanks for taking my questions. First question, just on China and the recovery there. Just your thoughts on the sustainability of recovery in China for your products and future price pressure. Then aligned to that, just JB, you highlighted increasing confidence in the growing top line, and I note that you're sort of saying general medicines should be flat out to 2025. Do you feel confident enough to give a target like you give for vaccines and consumer in terms of growth now? It looks like it's all growth going forward, but just your thoughts there. Thanks.
Okay, thanks, Richard. Jo, we tried a couple of times. Maybe you want to submit a question online if you can, and we'll try again a little bit later. Sorry in case it's our responsibility. Let's go to China. Olivier, Charmeil, maybe you have some views on the outlook?
Thank you. The market has suffered, of course, in 2020, mainly due to COVID. The definite number is not yet known for the decrease of the market, but probably in the range of 10%-11%. The market is going to bounce back. We are expecting for 2021, a growth that is going to be significant, 6%, 7%, 8%, not to say more. Of course, as there has been price pressure with the implementation of VBP in the last two years, we see that, of course, the volume growth continue to be very strong on our end, and we are very happy with our performance, both on Plavix and Aprovel, further to the implementation of the VBP. The China market remains a volume market on general medicine and on specialty, of course.
We continue to see with the registration of Dupixent and the start that for us, in the future, a significant portion of our growth will come from specialty.
Thanks, Olivier. JB, why are you not providing guidance on the future of the business?
Well, Richard, I'm glad you captured my optimism. That's fine, and that's effectively where I am. We have, I think, a guidance which is quite clear for 2022, with this BOI ratio, and yeah, we are really committed to deliver on it. We have, I think, a nice now set of guidance out there to help you modeling it. We will deliver on 2022.
Maybe could just add to that. It's our responsibility as an executive team and the wider organization to toggle that way. Remember back in Capital Markets Day 2019, we said that we wanted to be able to stick to the BOI and deliver and show you we could. You've just seen from the numbers full year 2020 that with 120 basis points improvement, that you can see the line to where we're going. You should expect us to deliver those things. Then we'll anchor from there. Next question, please.
We will take a final questions from Jean-Jacques Le Fur at Bryan, Garnier & Co. Jean-Jacques, please go ahead.
Thank you. We come back on the flu vaccine. For clarity, could we assume that you will be able to add again about EUR 500 million in sales this year as you did last year? If yes, how can we see the manufacturing capacity if you are successful with your COVID-19 vaccines, which I assume will take some of them for manufacturing? Is the new U.S. factory enough to deliver the additional flu doses? Thank you.
Thomas?
Thank you. Yes, Jean-Jacques. We have made sure that we always make sure that we secure the demand of our current vaccines. You know that we're manufacturing and supplying a lot of different vaccines that are critically needed, even in COVID-19 pandemic times. We made sure that our supply capabilities are growing, and it's not linked to the COVID-19 vaccines development that we are doing. We have everything we need to increase. As I mentioned before, the Fluzone antigen building is already up and running and starting to produce as we speak now for 2021 Northern Hemisphere. That's very important for us moving forward.
Yeah. Okay, good. Thank you. Next question.
Sorry.
Oh.
Looking at sales.
Yeah
Could we assume that you will be able to add again EUR 500 million about?
No. No. Again, the story of influenza, it's going to be a growth trajectory, which is a question in between growth from differentiated vaccines versus non-differentiated vaccines in a market that most likely in non-pandemic period compared to pandemic period will be probably lower. I expect us to perform well in a declining market for flu just for next year, but we are not in the magnitude of the EUR 500 million, of course, because we are not in a pandemic situation at all. You need to look at the continuous growth compared to the average trend of over five years, for example.
Okay, time is over for this first part. Let's meet in 12 minutes for the Capital Market Day. Thank you, everyone.