Good afternoon, and good evening to Asia. I'm Eva Schaefer-Jansen , Head of Sanofi Investor Relations. Welcome to this event. This is the fifth in a series of five R&D events highlighting the accelerating pipeline momentum building within Sanofi R&D. Today, we will focus on the phase II-B results of nirsevimab, just published in the New England Journal of Medicine. As usual, you can find the slides to this call on the investors page of our website at sanofi.com. Next slide, please.
I would like to remind you that information presented during this event 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 [Non-English content]. For a description of these factors. Next slide, please. I would like to introduce you to our speakers today.
We have here Thomas Triomphe, Global Head of Sanofi Pasteur. We have Su-Peing Ng, Global Head of Medical Sanofi Pasteur. Also, Jon Heinrichs, Global Project Head, nirsevimab from Sanofi Pasteur, and John Shiver, Senior Vice President, R&D, Sanofi Pasteur. Thomas will make some introductory remarks, and then Su-Peing will describe the major public health burden of RSV, after which Jon Heinrichs will discuss the details of the phase II-B results. John Shiver will then wrap up with concluding comments, including an update on the phase III program. We will be joined then for a Q&A session that's going to close this call by some members of the executive committee. With that, I would like to advance to the next slide and hand over the floor to Thomas.
It's better if I unmute. Thank you very much, Eva. And welcome everyone. Thank you for participating. Speaking on behalf of my colleague here at Sanofi Pasteur, we are absolutely thrilled today with the publication of the detailed phase II-B results that you have probably seen in the New England Journal of Medicine. This trial is the first of three pivotal studies for nirsevimab, a potent expanded half-life monoclonal antibody for the prophylaxis of RSV infections in all infants, done in collaboration with AstraZeneca. As many of you know, RSV is a major disease, a major public health issue for all infants. It is today the leading cause of hospitalizations in infant in the U.S. and in fact, in many countries around the world. Actually, in developing countries, in particular, RSV is there the leading cause of infant mortality.
We do believe today marks an important development in the fight against this pathogen, and we do believe that nirsevimab may represent a truly transformational asset, one which offers a population-based solution for the very first time with a monoclonal antibody. Therefore, it is a paradigm shift in the prevention of this disease. You may now move on to the next slide. Thank you. First, I would like to remind you on this slide our Sanofi strength in vaccines. These are actually the same strengths that have brought us together with AstraZeneca to develop nirsevimab in a highly successful collaboration. Sanofi Pasteur, as you know, is a global leader in both pediatric combination vaccines and influenza vaccines, and those two categories do account for about 2/3 of our sales. What does that mean concretely for nirsevimab?
Actually, it does mean we have an unrivaled blend of experience to drive the success of this product, assuming, of course, that we're going to receive the expected regulatory approvals. Our experience is based on a deep knowledge of respiratory disease and development of vaccines. Our insights into the operating models of pediatric vaccines, our ability to plan and provide effective season immunization, and our commercial leadership that has resulted in Sanofi Pasteur winning multiple blockbuster vaccine franchise. We do believe with nirsevimab we have such an opportunity again. With that, I now hand over to Su-Peing that will run you through the global health crisis that is this public health burden.
Thank you, Thomas. Good morning, good afternoon to everyone on the call. To set the context of the event, I would like to share with you a brief video demonstrating the huge burden RSV has on families.
Hi, I'm Dina. This is my RSV story. Winnie was my second daughter. I had never heard of RSV the whole time that Dylan, my older daughter, was growing up. My doctor described RSV as a cold on steroids. Looking back on it, I would not have described it that way. I would have described it as a horrible virus that causes your baby not to be able to breathe. They cannot eat because they cannot breathe. You're watching them 24 hours a day, holding on for dear life until they take that next breath. What I learned from this experience is just how vulnerable babies are. If there is anything that we can do to take this one virus and this one sickness off of a new parent's plate, it's worth it.
Here on slide seven, I'd like to illustrate the compelling evidence that the dominant disease burden for RSV is in infants during their first RSV season. By the age of two, almost all babies and toddlers would have been infected at least once by RSV. RSV the leading cause of hospitalizations in young infants, there is a clear unmet need for broad RSV protection, and currently, no RSV prophylaxis is available for the very large majority of infants. Slide eight looks at the U.S. birth cohort of nearly 4 million by gestational age. Less than 2% of infants are eligible to receive the only approved RSV preventative, palivizumab, also known as Synagis. In the U.S., only infants with a gestational age below 29 weeks, or those with congenital heart disease or chronic lung disease are eligible to receive palivizumab.
These restricted recommendations followed systematic evidence review by the American Academy of Pediatrics. Palivizumab also has a burdensome regimen that requires five injections over five months and carries a list price of EUR 7,000 per baby. As we look to the second and third bars of the chart, you can see the breakdown of the annual number of RSV hospitalizations and costs related to RSV hospitalizations for the three segments I've just introduced. Full-term infants, healthy pre-terms, high-risk infants eligible for palivizumab. Both the number of hospitalizations and the costs related to hospitalizations are dominated by the RSV burden in healthy infants, with up to 80% of the direct costs in this group. There is no vaccine available for this majority of the birth cohort. To summarize, RSV infection does not discriminate among healthy or pre-term infants, and any and all infants are at risk.
Roughly 98% of infants who are ineligible to receive the only approved prophylactic account for the vast majority of hospitalizations and associated costs. On slide nine, hospitalizations are clearly an important part of the overall cost of the disease, but they're only the tip of the iceberg, accounting for a fraction of the total cost. In purely financial terms, if we also add in the cost of emergency room visits, lost parental income, cost of outpatient treatment, and so on, the total cost of RSV in the U.S. runs to something on the order of $2 billion annually. Of course, the societal costs run deeper still due to the increased burden on the healthcare system during the already busy winter season and the emotional impact on affected families, especially those with infants with more severe RSV disease, as we saw from the parent testimony.
These slides, of course, only speak to the U.S., where RSV disease is better documented. With current global estimates, industrialized countries face almost 300,000 hospitalizations each year, and developing countries approximately 10 x that number. When we consider the likely underestimation of the true disease burden due to lack of routine RSV testing, you'll get a sense of the scale of this public health issue and the significant unmet need globally. Slide 10, my final slide, sets out the value proposition we envisage for nirsevimab, assuming our ongoing phase III trials successfully replicate the excellent outcomes of our first pivotal phase II-B study. We're aiming for universal coverage for all infants, irrespective of gestational age or birth month. Our ambition is to achieve a greater than 70% relative risk reduction of RSV-related hospitalizations consistent with the phase II-B results you will hear about next.
We expect to deliver this with a single Intramuscular Injection, which will offer a consistent level of passive immunity immediately, and over the entire RSV season. We intend to deliver this in a cost-effective package with a vaccine that is priced in line with other premium priced pediatric vaccines. Together, we believe this target profile for nirsevimab potentially constitutes a new standard of care in RSV prophylaxis. Essentially, a single passive immunization providing immediate, consistent, sustained protection for all infants during their first season when they're at most risk of infection and complications. We think this profile builds a highly compelling case for adoption in routine pediatric immunization schedules by all relevant payers and advisory bodies such as the ACIP in the U.S.
As Thomas stated earlier, we at Sanofi Pasteur have the expertise and the organizational ability to make this a major success and address this longstanding unmet need. With that, it's my pleasure to hand over to Jon.
Jon, you might be on mute.
He's lost his connection.
He lost his connection.
[Audio distortion].
Maybe John Shiver can take it.
Yeah, I can do that, and hopefully Jon can kick back in. Can you hear me okay?
Yes, we can. Thank you.
Okay. Well, thank you, Su. It's my pleasure now to take you through the exciting phase II-B results reported in full today in the New England Journal of Medicine. I want to begin on slide 12 by explaining the innovative construct of nirsevimab and how it facilitates effective and prolonged passive immunization. Nirsevimab is a novel recombinant human immunoglobulin-derived neutralizing monoclonal antibody. It specifically targets a conserved epitope on the pre-fusion conformation of the RSV fusion protein, meaning it prevents fusion of the virus with host cells. The smart piece of protein engineering substantially enhances the neutralizing activity of the molecule when compared to palivizumab, resulting in increased potency. The second clever piece of design work in nirsevimab is a modification of the Fc region, which extends the half-life to between 63 and 73 days. Nirsevimab's half-life extension is critical for our population-based approach.
The half-life is approximately three-fold greater than the 19 to 27-day half-life of palivizumab that requires monthly dosing, as Su described. In fact, in the phase II-B study I will discuss, the summary concentration of the antibody was still above the target levels in most of the infants treated at 151 days or approximately five months after immunization. This time point was deliberately chosen, as the average RSV season is approximately five months long. Turning to the activity of the molecule. Unlike traditional vaccines that prompt the body to mount an immune response to a foreign antigen, nirsevimab delivers a functional response itself by neutralizing RSV. This passive immunization approach not only provides immediate protection in contrast to standard vaccines, but also as a result of the prolonged half-life, it allows once per season dosing by a single Intramuscular Injection.
In recognition of the unmet need in RSV and the encouraging early clinical results, nirsevimab was granted Breakthrough Designation by the FDA and prime eligibility by the European Medicines Agency. Slide 13 sets out the design of the phase II-B study. This was a large pivotal study in approximately 1,500 preterm infants with a gestational age of 29 to 35 weeks. Unlike the majority of the phase II-B studies, this study had been designated pivotal by regulatory bodies in the U.S., E.U., and Japan, and it will be submitted with our two other ongoing pivotal studies as part of the registration dossier. The primary endpoint of the study was the incidence of medically attended lower respiratory tract infections, both in and outpatient, and caused by PCR-confirmed RSV infection for 150 days after dosing.
The comprehensive list of secondary and exploratory endpoints included the incidence of hospitalization due to the PCR-confirmed RSV infection, safety, Pharmacokinetics, anti-drug antibody responses, healthcare resource utilization, and caregiver burden assessment. You can see from the graph on the right side that the preterm infants were randomized two to one to receive a single dose of nirsevimab by a 50-mg Intramuscular Injection or a placebo prior to the start of the RSV season. They were then followed at various time intervals, including 151 days for the efficacy endpoint. As I mentioned earlier, this duration was chosen to mimic the length of the natural RSV season.
John, I'm on now if you'd like me to take back over.
I would love it, Jon. Please proceed.
My apologies, everyone, for the poor connection here. Thank you, John, for filling in during my difficulties. On this slide, I'm very pleased to show you the results of the phase II-B study that was published today in the New England Journal of Medicine. First, let's focus on the primary endpoint. Here we're talking about the incidence of medically attended RSV-associated lower respiratory tract infection, where we saw a very significant and profound reduction of 70% from a high of 9.5% in the placebo group to a low of 2.6% in the nirsevimab group over the entire 150-day time point. This equates to a P value of 0.001. Now turning to the secondary endpoint of RSV-associated lower respiratory tract infections-- sorry, hospitalizations. The incidence that we saw in the placebo group was 4.1%, and in the treatment arm of 0.8%.
That's a relative risk reduction of 78%, and again, a very significant P value of 0.0002. The relative risk reductions for both of these endpoints were consistent throughout the entire 150-day post-dose schedule which, again, conforms to the RSV season in the typical temperate regions of the world. It was consistent across geographic locations and, importantly, across both RSV subtypes A and B. This is very important because you may be familiar with some results of previous studies from other companies that showed a failure to protect against RSV B strains. Among other RSV complications, overall, the rates were very low, but no infants that were given nirsevimab were admitted to the intensive care unit or required ventilation assistance as compared with 1% rates in the placebo groups. This is critically important as this is an important consideration in treating these vulnerable infants.
Finally, only 0.4% of patients on nirsevimab required supplemental oxygen as compared with 3% in the placebo group. Although, of course, oxygen supplementation is a risk for all preterm infants, regardless of their RSV infection status. These are very compelling, very consistent, and very significant results that led us to believe the hypothesis has been confirmed and gave us great confidence to proceed in the phase III and phase II-III studies. If we can now advance to slide 15. Here, I want to drill down a little bit deeper. Here we're looking at two subsets of subjects, both those that were very early preterm infants that were between 29 and 32 weeks gestational age at the time of birth, as well as infants that were slightly older, between 32 and 35 weeks gestational age.
What you can see here is that the results are very consistent across both groups, with either a 74% or a 70% reduction in these two populations. The consistency of this data led us to start a phase III study called MELODY, which John will tell you a little bit more about in some detail, as well as a phase II-III study in which we're comparing nirsevimab to Synagis. If we move now to slide 16, please. I will focus on the safety data. Here, I'm very pleased to report that the overall safety profile was similar to the placebo group. The incidence of adverse events were similar between the two groups, and there were no notable hypersensitivity or anaphylaxis reactions. In addition, the anti-drug antibody rate was very low and was not correlated with any effect on either safety or efficacy over the entire safety readout.
Of course, we'll need larger number of subjects to fully address the safety profile of this molecule, and we are looking at that in the phase III and phase II-III studies now. Next, on the next slide, I want to point out something that's critically important. Here, I want to compare the possible uses of maternal immunization, like some of our competitors are developing, versus an active immunization in infants and a passive antibody transfer like we are using with nirsevimab. The bubble that has been drawn on this figure highlights the fact that maternal immunization typically provides protection to infants for a period of time that's about three to four months following the delivery of that infant. Whereas, because we can deliver nirsevimab just prior to the RSV season, we can time that antibody and give a consistent dose that will protect those infants for an entire five-month season.
And this is really the message that we want to share behind the idea that nirsevimab is appropriate for use in all infants. Maternal immunization brings a number of challenges. First of all, antibody titers are highly dependent on the timing of a mother's vaccination. Second, even with an optimal vaccination timing of the mother, antibody titers are likely to fall below an effective threshold at month three or earlier. This is critically important if an infant is born out of the RSV season, which remember, is five months long. Active immunization in an infant is not appropriate either. Because an infant's immune response is not fully developed at the time of birth, it's not possible to immunize infants at their most vulnerable period of time.
Furthermore, even if you were to immunize these infants, you would have to wait for weeks to months for an antibody response to develop. Therefore, we fully believe that passive immunization with a monoclonal antibody is the optimal way to prevent RSV disease in these infants. The reason for that is because you can give a controlled dose of antibody, and you can time that antibody to occur just prior to the RSV season, and the antibody can provide instant protection to those infants. So, therefore, we're developing nirsevimab for the treatment and prevention of RSV disease in all infants prior to their first RSV season and for infants with congenital lung and heart disease problems prior to both their first and second RSV seasons. If we can move to the next slide, please.
This is a rather complicated slide, and I want to walk you through it a little bit slowly. Here we're comparing the effect of maternal immunization, where we've modeled a four-month protective window on the right-hand side with the use of a monoclonal antibody like nirsevimab with a five-month window as shown on the left. If we focus on the right-hand side, the first thing to notice is the red bands on the graph. Those are the RSV seasons. For an infant born, for example, in the month of September, at the bottom of this figure. They would have a maximal circulating antibody titer that would wane and essentially not provide protection after about December. That means that for a fully half the RSV season, those infants would have suboptimal protection following maternal immunization.
Similarly, an infant born in June would gain no benefit from maternal immunization because the antibodies would have fallen below the protective level by the time an RSV season even begins. Conversely, on the left-hand side of the figure, you can see that regardless of when an infant is born, a monoclonal antibody like nirsevimab would be able to be given just prior to the season or during a season, if the infant's born during the season, and provide protection for the entire RSV season. If we move then to slide 19, I want to get back to a little bit of the data from the phase II-B study. I mentioned before that we monitored efficacy through the entire RSV season, or 150 days.
The data from the pharmacokinetic analysis of serum concentrations of nirsevimab demonstrate that the antibody level is above what we determined to be the effective threshold in animal models, which is the dotted line shown on this graph, for about 240 days. Therefore, it is possible that nirsevimab provides protection for a period of time that's longer than five months, and this may be important in regions of the world where the RSV season is unpredictable or stretches beyond a five-month period. Of course, after 360 days, the antibody level has decayed to well below the protective threshold, and that's where we feel a vaccine for RSV can be effective. John will talk to you a little bit about our vaccine data in a few moments. However, in our phase III design, we'll be following respiratory tract infections beyond five months post-dosing.
The potential to extend this protection beyond five months would be very important, as I mentioned, for regions of the world that have longer RSV seasons. If we move to slide 20, please. On my final slide, I want to compare the licensed product palivizumab or Synagis with our monoclonal antibody nirsevimab and maternal vaccination. We start with applicability to the annual birth cohort, as Su t old you before, palivizumab is restricted because it's dosed on a monthly basis and because of its high cost to a very small subset of infant population. That is about 2% or less, depending on the recommendations in a country. That means that that restriction is to infants that are severely premature, less than 29 weeks gestational age, or have chronic lung disease or congenital heart disease associated with prematurity.
Nirsevimab, we hope, will be applicable to the entire birth population, therefore protecting the 98% of infants that are not currently afforded either a protective vaccine or antibody and have no treatment options. Maternal immunization is really only applicable to those kids that are born as full-term births or near full-term births, and ideally, those that are born in the season or just prior to the RSV season. If we turn next to the achievable immunization rates, nirsevimab immunization, we believe, could be achieved in about 90%-100% of cases if added to pediatric schedules. Maternal vaccination really depends upon a variety of factors, including the health status of the mother, and would be expected to be achieved in only about 20%-40% of women.
If we next compare the observed efficacy, we of course, do not have yet any data showing efficacy of maternal immunization approaches for RSV. However, we do have historical data with palivizumab from two studies, which were conducted several decades ago, to indicate that that antibody provides protection of between 45% and 55% against hospitalization. As you have seen in the phase II-B data shown to you today and published in the New England Journal, nirsevimab achieved a 78% reduction in RSV confirmed hospitalization. Finally, treatment burden. We've talked a little bit about this before. Palivizumab requires five monthly injections and is therefore a burden to parents and to the infants that receive the injections. Unlike palivizumab, nirsevimab would be given as a single Intramuscular Injection, providing coverage for the entire RSV season.
We at Sanofi Pasteur are absolutely convinced that the immediate controlled protection offered by nirsevimab has the potential to make it the new standard of care for all infants in their first RSV season, as well as for high-risk infants in their first and second seasons. We believe this is a revolutionary solution, providing sustainable RSV coverage for the entire first season for all infants and would provide great value for all these kids. I hope that the phase II-B results and the additional discussion I have provided have convinced you of this. With that, it's my pleasure to hand you back to my colleague, John Shiver.
Well, thanks, Jon, and thank you all for taking the time to listen in. I want to make some concluding remarks before we turn the call over to Q&A. On slide 22, nirsevimab is a culmination of around 60 years of research and development into RSV. The road here has been especially a long one since the virus was first identified in the 1950s. In the intervening years, multiple preventative approaches have been pursued without success, including investigational vaccines and immunization strategies based around inactivated viruses, viral subunits, and monoclonal antibodies. Today, the only commercially available immunization against RSV is palivizumab. This was approved 22 years ago, and as you heard from my colleagues, it's restricted to use in a small minority of infants at the highest risk of RSV-related sequelae.
It's been a long wait, but with nirsevimab, we think we finally have the potential for a new standard of care in RSV prophylaxis. The phase IIb results, as described, met our highest expectations and have provided us with a great deal of confidence in the upcoming pivotal studies. I can tell you, the excitement surrounding this asset extends to the very top of Sanofi. If you listened in for our Capital Markets Day in December, you will have heard our CEO, Paul Hudson, highlighting nirsevimab as one of the six potentially transformational assets in Sanofi's pipeline. For Sanofi Pasteur, we won't stop there. We want to build a portfolio of approaches towards RSV that additionally covers infants prior to their second and third RSV seasons. To this end, we're investigating next-generation live attenuated subunit vaccines, which could be delivered intranasally.
These are currently in phase I-II and so are still some years away. Nonetheless, we think they could represent a complementary and comprehensive approach to limiting the impact of RSV alongside nirsevimab. On slide 23, let's move ahead now to our forward plans for nirsevimab. Slide 23 sets out our three pivotal studies. The goal of our pivotal program is to generate data across the entire birth cohort for all gestational ages. Our pivotal phase II-B study discussed today covers the gestational age group that sits in between, in the middle of our three target populations. Two large studies are ongoing. The MELODY study is a placebo-controlled study in approximately 3,000 full-term infants, which is on track for a planned completion in 2023.
This study will determine the degree to which nirsevimab is able to prevent medically attended RSV-confirmed lower respiratory tract infections, and it will also confirm the safety profile. The MEDLEY study is a descriptive efficacy study with a primary endpoint on safety versus palivizumab in approximately 1,500 palivizumab-eligible infants, specifically preterm infants in their first RSV season and children under 24 months with congenital heart disease or chronic lung disease in their first and second RSV seasons. This study, which is on track for completion planned in 2022, will examine the safety profile, Pharmacokinetics, and anti-drug antibody response, as well as efficacy in these high-risk infants. The three studies will form the basis for regulatory submissions, which we are targeting for 2023. As I mentioned during the vaccines outbreak at our CMD, this will potentially set the scene for a growth contribution to Sanofi Pasteur from around 2025.
Slide 24 gives you some more detail on our earlier-stage live attenuated RSV vaccine programs. Here, as Jon mentioned, the concept is to provide active immunization to infants in their second and third RSV seasons, complementing the use of nirsevimab in the first season. For competitive reasons, we cannot disclose too much information on the construct and planned positioning of these vaccines. You can see the graphic on the right side demonstrated both safety and immunogenicity in seropositive and seronegative infants as young as six months of age. Preliminary data from a study conducted by the National Institutes of Health and Johns Hopkins University suggests that our approach shows antibody activity likely to correlate with protection. The early signals are promising, and we look forward to additional readouts from the phase I-II study.
Together with nirsevimab, we believe this would comprise an industry-leading portfolio of immunization approaches for the control of RSV for all infants. On my closing slide, I just want to reiterate the key take-home messages on nirsevimab. We're aiming for the cost-effective RSV prophylaxis in all infants, irrespective of whether they are pre or full term. The data published today from the first of three pivotal studies supports our ambition of an approach that aims for 70%-80% relative risk reduction of RSV complications. This compelling clinical profile would be possible as a single injection for all infants for their entire first RSV season. As Su said, if we meet this target profile across our pivotal clinical program, then we are confident nirsevimab has the potential to become the new standard of care in RSV prophylaxis with broad adoption into pediatric immunization schedules.
This, in turn, would finally allow healthcare systems to address the leading cause of lower respiratory tract infections and respiratory hospitalizations in infants and the resultant infant mortality. With that, I would like to hand over to Eva to start the Q&A. Thank you.
Thank you, John, and thank you to all presenters. For the Q&A session, our presenters will be joined by Paul Hudson, Chief Executive Officer, John Reed, our Global Head of R&D, and Jean-Baptiste de Chaillou, Chief Financial Officer. We would like to ask you for today's call to focus your questions on RSV or related topics. All other questions, we are happy to take on in investor relations after the call. I would like to hand over to Natalie to remind us how to ask questions.
Thank you, Eva. You have two options to participate in the Q&A. Option one, if you would like to ask a question, please click the raise hand icon at the bottom of your screen. You will be notified when your line is open to ask your question, and please make sure you unmute your microphone. Option two, you may submit your question by clicking the Q&A icon at the bottom of the screen. Your question will be read by our panelist. We are now ready to take the first question from Graham Parry at Bank of America. Graham, please go ahead.
Great. Thanks for taking the question. Firstly, I wonder if you could just help us understand the ability to manufacture this antibody at scale and at the cost which would allow you to come up with a pharmacoeconomically favorable offering to healthcare systems. Secondly, any data to support the idea that the protective effects in preterm births are translatable to full-term infants. Thirdly, if you could just remind us of the economics and control of development and sales and marketing between yourselves and AstraZeneca, and any intellectual property on the antibody as well? Thank you.
Thank you very much, Graham. Just to recap, maybe some of the questions will go to Jon Heinrichs . Especially maybe Jon, I know you're not a manufacturing specialist, but if you can say a couple of words maybe on manufacturing, on most importantly on how we move on from preterms to full terms, and a little bit about the IP space. If you want, I can complete with some elements on the financials of the deal.
No, very happy to. Thank you for the opportunity. The first thing to note is that we are the commercial lead on this product. AstraZeneca remains the development and manufacturing lead. I would refer questions and specifics about the manufacturing of the product to AstraZeneca. The one thing I would say on that is that we maintain our commitment to making this product available in a cost-effective manner to all infants. Clearly, we anticipate that it will be priced in a way to do so, such as in a premium-like vaccine price manner. The second question is how does the phase II-B data translate into healthy infants? What I would point out here is that the phase II-B population, although premature, were healthy premature, and not a Synagis population. They were 29 to 35 weeks gestational age.
We believe this is a strong indicator of the efficacy of the molecule for both the Synagis-like population, those very premature infants, as well as it is a good predictor of what will happen in the MELODY study in the full-term healthy infants.
Maybe I can complement that. You had an additional question on the financials part of the deal, Graham, if I understood correctly. As you understood from Jon, basically this is a profit share, cost share deal. Sanofi will lead the commercialization, and therefore will book the sales. In terms of the initial deal that was done, I think that was communicated that there was a EUR 120 million up-front payment and close to EUR 500 million in terms of achievement of different milestones. Next question.
The next question is from Laura Sutcliffe at UBS. Laura?
Hi, thanks for taking my questions. Do you have any thoughts on the characterization of evidence of anti-drug antibodies here? I think your phase II-B data look quite a lot better than some of your earlier data. Secondly, do you think there's any room to compress the trial timelines here? Do you really need three to four whole RSV seasons, which I think is what you would have if you took into account both the northern hemisphere and the southern hemisphere, to get the MELODY trial done? Then maybe lastly, if you do go for a premium vaccine type price, do you worry that a price that low might call into question the price points of antibody use in other areas of medicine? Thank you.
Maybe I can take the pricing question first, and then, Jon, I will return to Jon H. Sorry, we have many Johns. I will return to you on the first two parts of the questions. Regarding pricing, great questions. Just to be very clear again, we are 100% committed to make sure that we're going to tackle the burden of disease of RSV. This is only possible if you tackle the burden of disease of RSV in all infants. That's why we are clearly going for a premium price vaccine strategy for all infants. I think there was a question about, okay, can you be a bit more explicit about what that means? Well, personally, when we think about premium priced vaccines, I'm thinking about here it's one injection.
So, basically it's one injection which is the equivalent of a full course, I would say, of a PCV vaccine if you wish, or a full course of HPV. That's the order of magnitude that I consider being a premium priced vaccine. Just maybe to complement that, because I think that I've seen some elements recently in the financial publication about this. I will consider that I've seen some comparison, for example, to rotavirus vaccines. For me, it's very interesting to see some comparison with rotavirus vaccines in the sense that it's seasonal, it's in the sense that in the infant population also. If you could take a step back and look at the burden of disease, that's very different. The level of hospitalization and the associated cost to this hospitalization for RSV is multiple fold times what it is for rotavirus infections.
Again, I think there are some commonalities, but if you think about the benefit this product will bring in terms of really having a huge impact on RSV disease, that's really thinking about a full course of PCV vaccine or a full course of HPV vaccine. That's how we think about pricing. Jon, you want to tackle the other questions?
Yeah, sure, Thomas. I'm happy to. The first question related to the data that we saw in the phase II-B publication on anti-drug antibodies. You are correct to say that some earlier studies suggested, one study in particular, a higher anti-drug antibody rate than what we saw here. Here, the rate was very low. I think it's much more in line with expectations that have been seen with Synagis and with other antibody products. What's important to remember is that even when we saw anti-drug antibody, it did not correlate with either efficacy or safety. In other words, there were no untoward effects of anti-drug antibody here. We're very convinced that that's a good signal and a real signal, and that it will remain low in the future. Second question was about timelines, and whether we need three to four RSV seasons to complete the study.
I would say that we're doing everything we can to accelerate this program right now. We're considering all possible ways to do that. It's very difficult to predict right now in the face of a COVID pandemic, when we can complete this study. That's really because of two reasons. One, it's difficult to recruit and retain patients, and we have to be concerned, first of all, with the safety of these infants and their parents. Second, that circulating COVID and the population response to that really is impacting the spread of RSV throughout the world. To have a full efficacy readout in this study, we really need to be able to study how the antibody prevents RSV. If RSV is not circulating in the population, it's very difficult to do that.
So, right now, we're maintaining the timelines that we've talked about today, and we'll continue to do everything possible to accelerate those timelines, because we believe this is critically important to get this antibody out there, to begin preventing RSV.
Thank you, Jon. Next question.
The next question comes from Seamus Fernandez at Guggenheim. Seamus? Seamus, you may be on mute. No. Okay. Yeah. Please go ahead, Seamus.
Okay, great. Can you hear me now?
Yep, we can. Yeah.
Perfect. Thanks so much. Just one question. It's our understanding that, can you just help us understand your coverage of both RSV type A and B with regard to the current antibody formulation? Secondarily, in terms of some of the older vaccines that we've seen attempted in the past, can you just help us understand whether or not the agency has demonstrated greater flexibility with regard to the types of endpoints? I know it's possible that maybe we see with an active vaccination rather than nirsevimab passive vaccination, that again, some have shown a reduction in disease burden, but not necessarily hitting the endpoints of disease avoidance or event avoidance. Just love to know where you see active vaccination evolving. Thanks.
I think you might be here again for the story. How nirsevimab is going to prevent both types A and B.
So.
About passive versus active and the perceptions of the regulators.
Yeah, so, so.. On the first question, clearly the data in the phase II-B study that we released today indicates that nirsevimab is efficacious against both A and B serotype strains. This is consistent with all the surveillance data that we've looked at pre-clinically with our collaborators, where nirsevimab neutralizes the vast majority of A and B strains that are circulating worldwide. We know the epitope is highly conserved, and we have no expectation that it will not protect against both A and B strains. The second question I think is more about the regulatory environment and do we expect that there will be some leeway for either vaccines or antibodies that maybe missed their primary endpoint, but are close, you know.
We don't see that as the case, and we're very happy to say that we have met both our primary and secondary endpoints in this study and that we stand by that data. What the agencies decide to do for other companies that maybe have missed their primary endpoints, I'm not really ready to comment on.
I think if I can add, Jon, whether it's for influenza, pertussis, or any of the other respiratory infections, agencies typically want to see lab-confirmed infection rates as well as the prevention of hospitalizations or other outcomes that are also meaningful.
Thank you, Su and Jon. Next question.
Next question is from Mark Purcell at Morgan Stanley. Mark, please go ahead.
Yes. Thank you very much for taking the question. Just a couple. Firstly, are RSV mutations an issue here? Is this a theoretical sort of concerns around sort of mutations in the F protein, the target of this product? Secondly, just in terms of theoretical safety concerns, both with a vaccine as well as a passive approach, are there any risks on the vaccine side of ADE, for example? Just any comments there would be great. Thirdly and lastly, are there any other diseases where a passive immunization approach would be applicable and do you have any projects that you could discuss at this stage?
Thank you very much, Mark. Mutations, and safety. Jon H., Su, or John S. Jon H. maybe start and then any other project, maybe this one will be for John S.
Yeah. Great question. In terms of mutations in the F protein. That remains a theoretical risk and one that we have to follow. As you know, that epitope that nirsevimab targets is a very conserved epitope. Our colleagues and others are doing surveillance globally, looking at strains that are circulating today, and so far we have a lot of data to demonstrate that nirsevimab neutralizes in vitro, both A and B strains that are circulating to date. What happens once widespread distribution of nirsevimab occurs remains to be seen. We believe that this epitope is very important to the function of the virus, and therefore is likely to be highly conserved. The second question related to safety, I think particularly related to ADE. All I can say is safety is critically important in all of our studies. We monitor that.
We have not seen any evidence either with nirsevimab to date with the vaccine that we're studying, or I think historically there's no evidence that Synagis induced an ADE response either. We're very comfortable with the safety profile that we published today in the New England Journal. Maybe Jon wants to comment on the utility of antibodies for other indications.
Yeah, thank you, Jon. I think this is important proof of concept for antibody prophylaxis for prevention of infectious disease, certainly pulmonary, but possibly broader. It certainly does open the door for additional diseases and we're evaluating that. There is a certain number of conditions that can restrict where this would be truly applicable. I think perhaps related viruses here to the RSV family is certainly an obvious place to explore it further. In terms of age group, given, I know there were some questions about moving to older populations like adults, actually the dose of antibody would be so much in an adult population as to preclude the ability to use an antibody in that population. Certainly opens some doors, we think, in certain respects, as I said.
Yeah. Not just from a delivery point of view in older adults, but from a cost of goods point of view, I think would be prohibitively expensive to try and use something like an antibody for prevention of disease in the elderly.
Thank you both. Next question?
Next question comes from Geoff Porges at Leerink. Geoff? Please.
I'm mute? Okay, I think I'm unmuted now.
Yes.
First of all, congratulations on the data. 70% reduction in hospitalizations and symptomatic cases is very impressive. Now RSV has been a holy grail for the pediatric world, and I'm not sure I would be generous enough to say this is truly a vaccine, but regardless, pre-exposure treatment is very positive. Several questions. First, could you clarify how you will explore the question of what effect this has on the later epidemiology of the disease and exposure? How, for example, do you know that school-age infants and young children won't get more severe disease after they've been treated with this antibody?
Secondly, do you have any data on whether this could be used in treatment when you've got a confirmed case? Obviously, you might need a higher dose, but it would seem sensible that you could treat an infant who developed symptomatic disease. And then lastly, are any of your prophylactic vaccines, your active immunization vaccines, being studied in school-aged children or the elderly? Thanks.
Maybe for the first one on the expected effect on later AP or exposure, maybe Su, you can take this one.
Sure.
John for the treatment options.
Yeah.
Jon H., sorry.
For sure, we know that the natural history of RSV is that actually we don't expect lifelong immunity. We can get infected with RSV several times through our life. What we do know is that it's actually, as we saw from the data, that U-shaped curve with the extreme ends of the age spectrum, where the severity occurs in the very young and the very old. Even if you felt that— if we.. If we believe the hypothesis that perhaps you delay an infection, into an older child, we know that older children, their respiratory systems are already going to be more mature, and they are less susceptible to a more severe disease.
Of course, we will be monitoring that, but we certainly also, that was one of the reasons that we have the full program that is anticipated to help bridge then from the first year of life to the second and third year of life with vaccine options. Of course, related to the older age range, we also want to make sure we can actually help address quite a sizable burden there as well in the seniors, together with the flu, RSV, and of course now with COVID. These are all RNA viruses that can cause considerable disease at that end of the age spectrum.
Yeah, and I think the next part of the question was about treatment, and we don't currently have any plans to study nirsevimab for treatment. I think there's two avenues to argue against that. One is the biology of the virus and targeting the fusion protein, which, as you remember, causes the fusion of the viral membrane to the host cell membrane. It's unlikely that once an infection is established, that you'd be able to access that fusion protein because most of the transmission of the virus from cell to cell occurs across the cell membrane. Unlikely that treatment would work, and the second piece is that's been studied with other RSV antibodies and has not shown to be efficacious for treatment. I think maybe John wants to speak a little bit about active immunization for older kids and the elderly.
Yeah, so we do.. We do, as we showed, have a live attenuated, actually intranasally delivered candidate for second season and beyond for the children. That's what they do in interactive immunity. They develop better immunologically. They should respond better to the vaccine. As we showed, there's data that's anecdotal at this point that the versions of the vaccine that we're working with that came from the NIH, look like they could be quite effective and safe in that population. That's the reason for how we're covering the pediatric population. In the elderly, it probably takes a different kind of vaccine approach than the ones that we're talking about for children. If you put a live attenuated vaccine into an older adult that has some pre-immunity, you'll probably neutralize that vaccine immediately, and it won't be effective. That's an important population to target.
We are working in that area as well. We hope ultimately to be able to have a comprehensive strategy for RSV disease across these populations with these several products or product candidates.
Thank you. Do we have a last question, maybe?
We can take a question from Peter Verdult at Citi. Pete? Pete, make sure you unmute your phone. Okay, let's try Luisa Hector at Berenberg. Luisa?
Hello. Thank you for taking the question. I just wondered whether you had approached the regulators about filing on the phase II-B data. Then maybe just to check, because obviously there are some maternal vaccine studies that are ramping up as well. Does that add an additional challenge in terms of your recruitment, or are there enough patients to go around? Do you think the antibody could yet be used in infants from mothers who had been vaccinated?
Jon H. and with the support of John S., do you want to take those questions?
Yeah, I think maybe I can start in reverse order. The question about, do we think that the antibody could be used in the infants that are delivered to mothers that have been vaccinated. We do not expect that the antibody would be interfered with by maternal vaccination. That, of course, would have to be established clinically. We are ahead. I think the burden will be on them to show that there's no interference there. The second question was about, have we considered approaching the regulators with the phase II-B data for licensure? We could do that. The study would support more than likely licensure. The safety database would likely not be sufficient. We'd have to do some additional safety analysis. The real problem is that this study was conducted in a very small subset of the infants.
The indication that we would likely receive would match that which was studied, which is infants that are between 29 and 35 weeks gestational age, thereby leaving out the majority of infants that need to be treated. There was one more part to that question, I think, Thomas.
Recruitment.
Recruitment challenges.
Recruitment.
So far, to date, we found that parents and providers are enthusiastic about volunteering for the phase III MELODY study. We don't foresee a problem there. Before COVID hit, at least we didn't anticipate issues for recruitment. We don't know what'll happen when the maternal vaccine comes into the clinical studies, we'll have to wait and see.
Mike, do you think?
It's important to remember there are no real options other than palliative for treatment. This is extremely common disease in this infant, young child population. Without an alternative, and the commonality of the disease and the severity of it makes it much easier to recruit under normal circumstances. We will see how we are going to do with COVID. Su, I am sorry. Go ahead.
Yeah. No, I think, previous experience with maternal immunization trials, it's actually very difficult to enroll pregnant women into those studies. Of course, we have the timing considerations that John highlighted as well. On the other hand, when you see the parent stories that were shown earlier, you know, people are very enthusiastic about enrolling for study with the monoclonal antibody approach. So I think, of course, it remains to be seen if we end up in the same sites or the same countries, but I would not anticipate recruitment challenges.
We do have the data from the successful efficacy study already, which does not exist, as Jon highlighted, and Su did as well, for the maternal.
Yeah. The other point to make there is that between the MELODY and MEDLEY studies that are ongoing, we have somewhere around 300 sites enrolled across both the northern and southern hemispheres, and I forget how many countries in total. We have broad representation, which allows us to kind of flip between countries and sites if we have recruitment problems on one site.
Of course.
Thank you. Next question. I realize there are many more questions. We'll get through all of them, no worries.
Thank you, Thomas. The next question is from Wimal Kapadia at Bernstein. Wimal?
Oh, great. Thank you very much for taking my question. Just coming back to, you mentioned the premium pediatric pricing structure. I guess I just wanted to hear any feedback you've had from governments and purchasers from such a strategy, given that's the complete opposite of what we saw with Synagis, which was priced much more like a drug. Tied to that, can we really expect to see penetration rates similar to other essential pediatric vaccines of greater than 90%, assuming that price point?
How far can nirsevimab actually go in these high-income countries? How much of an opportunity is it in lower-income countries? Should we be thinking similar volume/value mix across countries as other vaccine markets? Just a final clarification question from an earlier comment. You suggested PCV and HPV as a good benchmark. Should we be thinking similar price per dose, or should we be comparing against the full dosing schedule for those indications? Thank you.
Thank you, Wimal. Clearly, for a full course of those comparisons, as examples of what are premium price vaccines. Here it turns out that nirsevimab is so great that you need only one shot to get prevention. The idea is to get prevention. We're comparing it for the full course, of course. To your questions, of course, it's still early and we are just publishing phase II-B results to have in-depth discussions about pricing with anybody. These are still early indications. I do believe when you look at the impact of the disease, and we've had some mention of that before in the presentation from Su, that there is a significant burden of disease. Again, you can think of very, very significantly higher in terms of number of hospitalization, for example, than rotavirus, and that gives you an idea.
You see very high vaccination rate against rotavirus. Remember, this is the number one cause of hospitalization for infants in the U.S. You've seen before the rates of hospitalization for this disease, especially in the zero to 11 months years of age. We do believe there is a very important burden of disease. We do believe that not all procedures will be equal, and this one shot monoclonal antibody that is precisely giving you the protection at the time you need it with immediate onset, is the right way to tackle this problem. Therefore, we do expect a significantly high vaccination coverage rate or immunization rate, if you wish, especially in high-income markets. To have an idea, if you think about just Japan, EU5, and the U.S., we're talking about 8 million newborns per year. We do believe there is significant potential there.
Great. I think there was a comment earlier. This is considered as a holy grail, as Thomas highlighted, this has been long anticipated and much needed. When we've been interacting with some of the stakeholders, like the ACIP equivalents in these countries, they've been extremely enthusiastic, wanting to know the data, really highlighting they know their own data. They have a huge amount of respect for the burden that this RSV causes in the very young infant population, and are very, very much looking forward to seeing the data coming from our development.
And of course, this anticipation of the value is in line with the very nice phase II-B results that you have seen. Again, the huge impact on hospitalization, on infection is very important. This recognition, we believe, is also established by the fact that we have the Breakthrough Designation from FDA or the Prime status at EMA level.
Thank you so much.
Thank you. Next question.
The next question is from Peter Verdult at Citi. Pete?
Second time lucky. Can you hear me?
I can hear you.
All right, good. Just two, there's been so many. Just a clarification and an invitation. Just to confirm, is the antibody hitting the F protein in the pre- or post-fusion conformation? Then when we look at some of the competing approaches out there, you've got companies like Bavarian Nordic, doing a multiple protein approach, you have GSK talking up their RSV vaccine candidate. Any observations or compare and contrasts you'd be willing to share with the audience? I'll be interested to hear. Thank you.
Jon H., do you want to take this one, pre-fusion or not?
Yeah, that's the easiest question so far, Tom. I'm glad to take it. The antibody nirsevimab is specific for pre-fusion F.
The second part of the question was, if I understood correctly, Pete, about the comparison with the other approaches from the competition, correct?
Yeah. Any observations you're willing to share? I realize you probably don't want to say much, but anything you're willing to share?
For me, I don't know who is projecting the slides. If we go back to slide 20. I take that occasion, sorry. As mentioned before, we are very excited today because RSV has been, for a long time, the next big target in vaccines. We do believe that those results that have been published today in The New England Journal of Medicine are pivotal and critical because it's going to be a huge change in the way we prevent this disease. We have no way to do it except for the 1.6% or 2% instance that were in the indication of palivizumab. Here, we have now a way to do it for everyone, and I think that's the very important part. Of course, if I were you, I would look at recent news and say, okay, yes, it's the next best target in vaccines.
Yes, it's coming soon, but there are many players down the road. You've heard about all the phase I, phase II, phase III candidates that have been announced. You have Merck, you have Pfizer, you have GSK, you have J&J, and probably some others. I'd like to highlight one thing, is that not all approaches are the same. We do believe this slide that you have here in front of your eyes is very important to mention that. We do believe that the benefits of nirsevimab that you see in the middle is unprecedented when you compare to the other approaches. Maternal immunization, which a few of our competitors are pursuing for the same indication, protecting the early infants, is very different. Maternal immunization is not new in terms of procedure. You know very well that we know maternal immunization extremely well because we do it.
We have pertussis vaccines, we have influenza vaccines that are both, in various countries, recommended for maternal immunizations. But even the highest rates in those countries for maternal immunization are actually low rates and nowhere comparable to classical VCRs that you get into injecting into a young infant. When you want to be tackling the burden of disease of RSV, I think it's very important to look at how you do it best, and then you look at these numbers and see the ways the impact can have is very different from one approach to the other. You multiply that by the fact that it's a seasonal disease, and therefore, if you think about it, you would not give a flu shot to your parent in the month of April, if you're in the northern hemisphere season. So, same thing here.
You don't control when pregnancies will happen during the year. Really, I think that the impact you can seriously get into maternal immunization for this disease is highly questionable. nirsevimab is able to, with a proven now, phase II-B demonstrated efficacy, to really tackle this disease in a way that no other can do.
Thank you.
Next question.
We will end the Q&A with Simon Baker at Redburn. Simon?
Thank you. Thank you very much for squeezing me in. Two questions. Firstly, I wonder if you could share any of the health economic data that you have. As you say, the prevalence and cost of hospitalization in this setting is pretty high. I would have thought at the price point that you're talking about, the health economics are overwhelmingly favorable for the product. Any details you could share there would be much appreciated. Then secondly, do you perceive any logistical challenges in the real-world setting with folding the nirsevimab passive immunization into existing vaccination strategies, which are typically at quite well-defined time points, whereas this won't be because of the seasonality of the disease? Associated with that, can you give us a reminder of the typical time from approval to inclusion in vaccination schedules in the major markets? Thanks a lot.
Thank you, Simon. Su, do you want to take those first about the implementation in the real-world setting and how do you see it and maybe some elements about [S] economics?
Right. I think it depends, of course, on which countries we're speaking to. Countries generally have very good access to infants throughout the year, right? There are time points for vaccination in the first six months of life. There are also well-baby visits. Of course, there's a timing aspect with respect to the season, but given the numerous time points that a mother and the child will be accessing their physician or healthcare provider, I believe that as long as the programmatic aspects are well explained to the providers and the public health system is rolling it out, then there should be a lot of clarity in terms of how and when to deliver the dose of nirsevimab. I think, from a real-world standpoint, there are enough time points for access to address this issue.
Thank you very much. Any other question or was this the last one?
It was the last one, Thomas.
Just to conclude, maybe a few words. First of all, thank you very much to everybody for attending. We do believe, again, as I said at the introduction, that this publication is really a landmark in making sure that now we have a way to tackle RSV disease for all infants and not just a few selected part of the newborn population. I think it's a huge paradigm shift, it's going to be able to do it in one single injection that can be given at the time it's most required. Again, if you look at it from a programmatic perspective, logistic perspective, efficacy perspective, safety perspective, this is a very promising asset, we're highly excited by it. You probably understood that today. That's first point.
Second point, I would encourage you to discuss about RSV or bronchiolitis with whomever you're encountering around the room in every single setting during the vacations. You're going to see that it's highly frequent disease into the all newborn population. My daughter, now turning 15, has been immunized when she was just turning three months of age for three nights in the hospital here in [inaudible]. I don't wish it to anybody, as you've seen in the video. This is a real problem. It's been the Holy Grail of vaccination, has been discussed for many decades, now we are touching from our finger points the way we're going to be able to tackle this disease. Very exciting news. We do believe it's a great asset.
There are still, as mentioned by the team, two more pivotal studies to come that are running, and the results are expecting to come soon. It gives us also a bit more time to keep explaining the importance of nirsevimab and the burden of disease of RSV to make sure that as soon as we are licensed, we are in a position to make sure that as many kids as possible, all newborns, all population, are protected against this severe disease. Thank you very much. We're looking forward to further exchanges with all of you about RSV disease and nirsevimab in particular. Thank you.