Apart from today's presenters from Sobi, we also have Dr. Dan Hart here with us that will give his perspective on hemophilia from a clinical perspective, and now I will hand over to Linda, who will go through some practicalities.
Yes, hi, I'm Linda Holmström, and I work with Corporate Communications and Investor Relations as well, together with Paula. Hopefully, we will not run into an emergency in here, but if we do, I need to inform you that we have emergency exits over here and over there, and may I also remind you to keep your mobile phones off? The presentations today will be recorded and will be available online tomorrow, sometime during the day, so therefore, if you would like to ask a question, we have colleagues that will be walking around with microphones, so please put the microphones close to your mouth so we can hear you loud and clear so everything will be recorded. Today's program will be divided into blocks.
We will have an introduction, and then we will move into the business areas: Hemophilia, R&D, and then we will have a section on the pipeline as well. After each of these three, there will be a short Q&A, but there will also be a longer Q&A by the end of today. So if you haven't asked your question during these first Q&As, I can assure you there will be time. So by that, I will hand over to Guido Oelkers, our CEO. Please welcome.
Thanks, Linda.
It's my pleasure to welcome you here. As you hear from Linda, you're in safe hands. There are a lot of exit doors. I hope you will not need them as a result of our bad presentation, but more excited to stay longer and ask curious questions. So I'm very excited to be here. We felt, when we thought about this Capital Market Day, that it was a good time maybe to share some ideas that go beyond the format that we have typically in the quarterly earnings reports and let you a little bit in what is behind our thinking in hemophilia and why we believe that we have a clear play to grow what is basically behind the growth in Gamifant and why we believe that this is a very material opportunity for the group.
Also basically clarify a little bit what is this Synagis because we felt that there is no prize in life to be misunderstood. So we basically figured that we should try to make an effort to explain a little bit more deeply and then allow you to judge how to see this. So basically, I mean, and I think this is when I talk about this rather simple strategy, it feels like a broken record, but still, just a reminder. Let's say when we started off September 17, we said, "What do you want to do?" And basically, those four pillars still are valid. So clearly, we want to drive penetration with hemophilia. And at that juncture, we basically said, "Want to take more advantage of Specialty Care." Today, we articulated really that Specialty Care has a much stronger therapeutic focus.
Obviously, took note of the fact that for many of rare disease products, more than 50% of the earning potential is related to the United States, so we clearly understood that if we wanted to become a serious player, we needed to make a step forward in the United States, and then we also felt our late-stage pipeline obviously could benefit from a couple of additions and quite gratified to report back on the progress here, so what we basically said then is what we actually are doing, and this is always like in life, basically statements are very easy, but if you really want to know what the strategy of the company is, you need to just look at what they are doing, and we hope to convince you that basically this is what we are doing.
So really fantastic here, first Capital Markets Day, and what we want to give you a sense of that the company is in very good shape and that we are bullish about the future. Sure enough, there's volatility, but this is what strengthens the focus and what gives us even more encouragement to do what we think is in the best interest of the company. When we basically think about us, we have obviously a new management team. We have just made a new addition in the United States because we felt, let's say, that we could benefit from somebody with a different lens helping us here. Basically, Amy Pott has just recently joined us from Shire and very excited about her being on board and driving this business to the next level.
She was running a $1.2 billion business at Shire and clearly has the right relevant experience in the United States. We have two and a half times the business that we had in 2016, and basically quite like it because somehow our earnings guidance seems to resemble what we had in top line in 2016, so a bit of change that happened to the company, and for us, it's basically about managing this change, managing the appropriateness of the organization to cater for this, but really happy that we are not only about aspiration, but that we basically can talk about what we have accomplished, but this not to be satisfied, but to encourage to take this business to the next level, and hemophilia patients obviously more than tripled in the same period of time, and now we have a very significant position, as you will see.
And we have historically been a little bit more ambiguous around shares. I mean, we have now, I think, a good enough understanding in detail, obviously, of the position, and we will share with you some shares on a patient basis, but also on a value basis as far as we understand. And this is not an accurate science, but we think it is sufficiently indicative for you to get a sense where we stand today. Obviously, I have done two significant deals, one being Gamifant, a license agreement with a view, let's say, that there could be a second step. And we have launched Gamifant emapalumab at the end of last year in the United States. And as you have seen from the Q1 results, it is off to a really good start. And we have then integrated the Synagis business.
I mentioned it at the earnings call that hasn't happened in my career, that basically we made an offer to 133 people and all 133 accepted. So this gives testament to the fact that the team that used to come from the MedImmune side is very close to the cultural environment that we represent. And obviously, with those acquisitions, we built significantly our U.S. presence. A year ago, we had 58 people. Today, we have 300. So quite a bit of change that has happened. And that's, I think, is quite a good evolution for the group that positions us well also for the next moves.
And then the strengthening of pipeline that came with the Synagis acquisition, we want to let you in a little bit into 8897 to the extent that we can talk about, granted that the readout of the phase II-B is expected by the end of the quarter. But we have some insights that we want to share with you and also share with you, obviously, more on BIVV001 to the extent that we can do this at this juncture. So basically, that's the team. Very happy, very proud to be part of this team that is making the change happening. Today, as Paula has pointed out, we cannot, as part of this format, let's say, let everybody present about his area or her area of responsibility.
So we picked a couple of them that basically we felt are relevant for the discussion that drives value, meaning hemophilia, meaning immunology, meaning R&D and medical, obviously, in this regard, and then providing a view on the overall financial standing that Henrik will take over. So quite a lot of new people. Very happy when you have Henrik, who many of you probably know, let's say, who was CFO of Recipharm before and Meda. And they got quite accustomed to do deals. We hope that, let's say, that Henrik is not going to lose the habit. And we hope that we can leverage on his strengths in this regard. Phil, who has wealth of experience in hemophilia previously from Pfizer, more than a decade. Norbert, a lot of experience from Roche and Aventis and Takeda and also from other rare disease companies.
We're very happy to have him looking at Specialty Care and immunology in particular. Armin, having been a treater himself and being with companies like Baxter and now Shire or Takeda, and now happy to have him here and obviously wealth of experience from a treater, but also from a medical management perspective. Milan, who joined us from Novo Nordisk and bringing a wealth of experience here from a development, but also from a research angle. Torbjörn, previously with Takeda, Nycomed. Very happy that he accepted the role and joined us a couple of months ago or half a year now ago. Christian, who used to be with AstraZeneca and a couple of other companies, happy that he joined us.
Sofiane is somebody who has done enormously well for us in the southern part in France, but we felt that we had to expand his role to the southern part of Europe. Amy I mentioned. Anne-Marie, who joined us from Biogen and basically upgraded our skill set on how to produce biologics, but in particular, obviously having an enormous insight on how to take charge of the supply chain and production of factor products. Paula recently joined us. It's fantastic that wealth of experience also with companies such as Meda and upgrading us in Fredrik, also previously Pfizer. So it gives you a flavor. Very broad experience in the team. Very blessed to be part of this. And as I said, we will only introduce a few in order to keep the time. So basically, when you look at it, this is our little journey.
We started at the end of 2016. I joined in May 2017, let's say, with 5.2, and then it was just basically about the so-called "realization," but I think we got stuck in and were able to increase the switch rate in the hemophilia business quite considerably, and that basically propelled growth, and we were very happy that we were driving growth at this pace. When you look at last year's compounded rate of over 30%. The guidance you have seen here, the uplift in the guidance obviously is driven by the Synagis acquisition to a large degree, but also with organic growth, and that we would like to explain to you.
So basically, really a phenomenal development for us and also now to see that earnings are becoming quite material and increasing the strategic degree of freedom of the company to make choices and embark on more development projects, but also invest into the core business at a significant rate and be very competitive in the areas where we play. So what we basically do is what we try to make sure is this company was always very strong in terms of intelligence, in terms of R&D related matters. And I think over the last years, what we have built up is quite a bit of savviness and assuredness in the commercial setting, which to be quite frank, we probably also need now as we go along to make sure that we assert ourselves in the territory.
But when you think about the company, really, we are a company that was built on partnerships and transactions, and here quite a couple of them mentioned, with obviously the latest ones being emapalumab and Synagis and with the takeover of Bioverativ by Sanofi. We're now happy to be a partner with Sanofi in hemophilia, but also for 8897, which is a follow-on compound to Synagis. So basically, when you think about it, and I will be a little bit more clear, we think, I think there's ample opportunity to grow this business. And when we started, we laid it out, we said, "We want to be a global leader in rare diseases." And we leave it up to you to basically say what constitutes a global leader.
We are now in the U.S. dollar, when you look at our guidance, give or take $1.4 on the exchange rate, maybe sometimes a little bit higher billion dollar company, so we are making great strides, but clearly, we have still a long way to go, and we want to build this business, and we feel encouraged by what we have achieved so far. So portfolio is very strong. This is what we believe and we don't want to slow down in terms of M&A and have strengthened our M&A function considerably over the last couple of weeks, actually, so when you look at it, we feel that we are in the right space.
Rare disease is still a space where a lot of growth is going to happen or has happened, but double-digit growth also about to happen in the forthcoming years when you believe many reports, and we can see this. This is an area high unmet medical needs, over 7,000 diseases still not adequately taken care of. So a lot of room for growth for a company like Sobi, and we clearly are totally focused on this space. When you look at basically the unmet medical need, even when you think about an area where you think, "Okay, Synagis has been around now for quite a while," but still, there is a lot of hospitalization ongoing.
There's a significant morbidity, and let's say, globally, very pronounced in the United States thanks to the availability of Synagis, much less, but still a couple of hundred babies who are not having access and who are affected by this disease significantly. So we are dealing not with marginal improvements very often, where we make a marginal improvement on convenience or improving a little bit the onset of action in a disease that is well controlled. We make very often a very significant impact, like we had, for instance, done in the tyrosinemia area, where many people now you have just met a patient 20 years old and being able to have a child of his own, which would be a couple of decades ago impossible without offering. So we quite gratified. I think we know our place.
We don't want to overemphasize this, but it's very gratifying to see that we make a significant difference to human health. This is what we expect: significant difference, for instance, in the HLH area. I think Norbert and Milan will share their thinking around this in much more detail. You get a bit of a taste of what kind of difference we affect. Also in the hemophilia area, I think Dan will show some photos and perspectives. It's not like this is an area that is completely well served. This is not a trivial disease. Clearly, it really makes sure that we will keep up our effort to try to do the best in patients' interest. This will be followed up by Armin and also by Phil.
So in summary, when you look at our portfolio, I mean, the way we look at it, and you look at our first quarter results, I mean, we see significant growth still in hemophilia. And when we look basically at the growth rates now with the long-acting Alprolix, I think it's important to note that we have not seen yet any slowdown of the absolute acquisition rate of patients. So there is a lot of speculation that you can have about what may happen or might not happen when new entrants are coming in. And that basically everybody has to decide this for her or himself. But what we see is that we keep going strong, and we feel encouraged to invest this area. We are obviously aware that over time, there will be a different growth momentum given the, let's say, the number of new options coming in.
But we are confident that we have really best-in-class products in our stable, and we are committed to them. We will share with you a little bit the theme, how we see the world, and how we believe that individualization, personalization, and intensification are important drivers that will speak in favor of our therapeutic option. We are totally committed on this pathway, and you will hear more content in a few moments. The other thing to note is obviously that when you see the results of BIVV001 that were published recently at ASH, you get a taste that we believe at least we have a big part of the future in our stable, particularly when you look at the trough level after one week.
We are convinced that BIVV001 has the potential to play a very important role in the future of hemophilia A treatment and compares actually quite favorably with what can be achieved also with new therapy. We are really bullish about the future, convinced that we have good products today. With Synagis, we want to also let you in a little bit that this is a growing product. We basically don't profess that this is a product with stellar growth rates over the next five years, but with strong growth rates, particularly when we do some touches to the business. We went through a very thorough exercise on how we can drive value in this category. Norbert will share with you a couple of those insights on how we think about Synagis and why we are so bullish that we are on the right pathway.
I will share with you just some thoughts on how to bring the Q1 into perspective and why we still believe that we have a growing product because I think it's important to get this right. And obviously, as we pointed out earlier, we wouldn't have done the Synagis transaction without 8897. And we believe that this is a very, very significant opportunity for Sobi, even though we were granted we will share only 50% of the earnings together with Sanofi Pasteur, but a much broader opportunity that goes beyond Synagis. Then we have a Gamifant, and you've seen the first quarter, only so much. This is really to a very, very large degree driven by true demand. So there's hardly any stocking in, and we hope to impress you with our Q2. And when you look at Kineret, this is a steady growth driver.
We had a bit of a moment of weakness in Q4 in the United States, but we have strong indications to have come out of this. This was a distributor change that this was not going the way we were hoping for, but now we seem to have figured it out again and are on a strong trajectory. So when you think about it, hemophilia, I just tee off a little bit to the main themes, not to take the sun away of the later presenters. The way we look at it, it's really for us, we want to bring patients into the situation that we can liberate their life, that they can live the lives they choose to, that with an intensification of personalization of therapy, they can have an active life.
So when you think of the 15-year-old child who wants to play soccer and who doesn't want to be a spectator because the trough level that it had is not sufficient to support this activity level, that this child can have the opportunity to have a normal life if she or he adjusts the injection schedule accordingly. And that's basically what we feel is a very important theme. So individualizing therapy, and we will show you the bleed rates that we achieve in this context. And we think that this is very, very important to patients. We don't believe that this is a panacea, but equally speaking, we don't believe that any other company has a panacea either, and that there is enough room. So what we do is we want to provide choice, and we are very obviously committed in the pursuit of this.
We basically believe that there's a lot of room for growth for us still in terms of penetration and in terms of internationalization. Yes, we have launched in a number of countries, but we have a lot of opportunity for us still to gain significant share. Products are good, and we believe that at least with BIVV001, we have a big chunk of the future. I think this is very important that we can interest the community to also stay connected with us from a research interest. When you think about the other arm of our business, immunology, in HLH, we clearly can see significant unmet medical need. It's a first-approved drug in primary HLH. I think important to note, while they are conventional treatment empirically used, they are not approved. We think that the market was waiting for an opportunity like this product.
Good start. I think you look at the Q1 results, we are very encouraged by it. And when you think about the opportunity related to the number of patients in primary, but also in secondary, and as we are now developing the product, and we will opening up the product also into stem cell, let's say, therapy. And then you get a sense that the opportunity for Gamifant is much, much broader. And we are very encouraged. But for us, it is about delivery. So we wanted to share with you insights, but we are not here yet to tell how you have to change your forecast. That's for you to assess. Anyway, encouraging start with Synagis.
Product is growing in market at 2%, and I will share with you a simple diagram that just should give you a sense how we see the product tracking. And with a growing scientific interest in IL-1, we also see a very sustainable growth momentum with Kineret. And there is utility of Kineret in numerous indications. We haven't yet, let's say, concluded on how to do the development plans, but we are working on this and would like to update you shortly. So maybe very briefly, because this was a question that was debated quite heavily, how to think about now Synagis. And I just wanted to share this with you. When we basically made the announcement on the transaction, what we said is midpoint 17, midpoint 18. So you had a full season. The product was tracking at $269 million, $269 million.
We know, and this is basically when you apply for half of the season, 2% growth, organic growth, and that's what we have seen, let's say, and this is around $4 million. Then there's a delta because the sales that were recorded were $287 million. That delta was under the stewardship of AstraZeneca. So I really cannot comment, and I don't want to comment on this. The only thing I know is when I looked at the inventory levels at the wholesalers, let's say, basically how they evolved, I had a $17 million deduction of inventory in Q1 at the wholesaler levels because they share with us their inventories. Yeah. That basically gives you a sense, and I know because we have missed out on $26 million of sales in the first 23 days that we didn't consolidate because we closed the transaction on the 24th.
AstraZeneca recorded $26 million of sales. Now, let's say, because we don't want to make forward-looking statements on the product basis, now what you have to look at this, and if you think about Synagis, you do the deduction, you come up, obviously, let's say that's the status of the product as we see it. And then you have to believe or not, that's for you to decide after you hear the presentation on Synagis, that we can keep growing the product at a certain organic rate and that our ability to unlock value, and Norbert will talk about this, in the different leakage points of the product, that this is at least as good as basically some of the structural inefficiencies that we would have to accept. And there's a minor increase of Medicaid, but it's minor, let's say, that we have seen in Q1.
And that basically potentially some of the inefficiencies that we may have to encounter in the supply chain, being smaller than AstraZeneca. We are convinced that we have a growing product, but when you think about the lens, then your lens, I think, it gives you a little bit of perspective on how we see the product. So when you basically adjust a like for like, then basically you do the deduction and you get a taste. But we know that the product right now, first quarter, this is what we commented on, has been growing organically or in market, what we can track at 2.2%. Yeah. So this is, let's say, we just wanted to provide you some data points. We are not in a situation now where we wanted to give you a forecast for Synagis.
The dilemma of Synagis is obviously that you have this very strong skewed sales development towards particularly the last quarter of the year, and obviously in the first quarter because of the seasonal effect. That basically makes it obviously difficult to judge. It's a bit like, okay, when are you showing us that you really deliver? The unfortunate truth is I can show you when we tell you what the Q4 results are. So that's the reason why what we can do today is provide you, I think, with a good takeaway where the product sits. So we think that the product will perform well under our stewardship. The other thing we were continuously looking at is we look at bolt-ons. That's anyway part of our daily practice and hopefully can show something. We are looking at selectively a geographic place.
But for us, the primary angle would be to make some bolder moves where we can, let's say, make a significant and material difference to the company because we just believe that this company is in such a unique position to be one of the leaders in rare disease, and it would feel like a huge missed opportunity not to go after this. And with regard to a couple of the key messages, we think we are in the right segment. We believe we have a very competitive portfolio. We will try to let you in a little bit why we are so passionate about personalization and individualization and why we believe that there is a significant opportunity for us to grow in this area for patients who really believe that it's important to them to grow.
Gamifant will talk to you about, will tell you a little bit more about the opportunity. Synagis, we let you in into what is our thought process on value creation. And then basically, Kineret give you an update and obviously an update on the main pipeline assets and quite gratified to tell you also that 003 is up for a good start. Yeah. So this gives you a little bit of a blend. So basically, I have the pleasure today to give you the more aggregated view. And now you get also when you have the tough questions, please refer them to my colleagues. They are well prepared. And let's say, but on this note, I like to hand over to Henrik because I understand when you talk to investors and analysts, they like to talk about the real stuff, about the numbers. So Henrik will lead you through.
Thank you.
Thank you, Guido, and hello, everybody. As a surprise, I will take you through some financials of Sobi, give an overview about that. I'm starting with, okay, there you go. I'm going to start with the revenue line. This is revenue by quarter since Q1 2017, both in total and by business area. As you can see, we are on a fantastic growth track. We have an average growth of 11%, and this is not by year, this is by quarter. It's, of course, driven by the success in hemophilia, where we have a development from SEK 700 million per quarter up to SEK 1.7 billion right now.
But it's also in Q1, we experienced a step change in the balance of our business, where we add, when we for the first time get a significant impact from the new products in immunology, the addition of Synagis and the successful launch of Gamifant. When it comes to the remaining Specialty Care business, it has a stable development despite the fact that we have now started to see some impact from generic competition of Orfadin. If you look at revenue in terms of regions, we, of course, have a very strong development coming from Europe, driven by hemophilia, but also other products. And here, of course, Gamifant is still to come. We haven't yet launched Gamifant in Europe.
So we have been, to some extent, quite a European company up until Q1 2019, when we got a real foothold in the U.S., making the U.S. for the quarter 1/3 of our sales. This means that we have a much more balanced geographical presence going forward. So we have now commercial infrastructure, not only in Europe, but also in the U.S. for further growth opportunities. Then if we move further down the P&L, we come to gross profit. And as you can see, we are on a very strong gross margin trend from the low 70s, now up to 76%, adding very highly profitable products in Q1. This is, of course, the result of a favorable product mix, but it's not only the product mix.
The fact that we sell more of our profitable products, more of our own products, and relatively less from products where we share margins with other people. It's not only this. It's not a passive ride. It's also the result of quite successful work in the management of COGS, where we've been able to take advantage of the increased volumes, where we've been able to, in particular cases, carry out tech transfers and as a result, get lower COGS. And then, of course, also efficiencies and improvements in our own manufacturing of ReFacto. So this is an ongoing positive trend for the company. What about OpEx? There seem to be some increases in OpEx lately. Well, we are in the process of transforming the company. We have, in addition to our previous business, taken on the whole development of emapalumab.
We are in the launch phase of Gamifant in the U.S., and Europe is still to come, and we've taken over the whole Synagis business. At the same time, we've competed very successfully in hemophilia, which is a very highly competitive area, so despite the efforts, we still have a very strong profitability in the company. We have EBITDA margins in the 40s. If we look at the OpEx and the impact from the new business, the new immunology products, well, the tall bars are sales and the short ones are costs. We can see that for a very long period, we had a very stable OpEx base of about SEK 700 million per quarter. It's only when we take on the new products, starting with the development activities of emapalumab, going through the launch and the takeover of the Synagis business, where there is an uptake of expenses.
We are, of course, taking advantage of our opportunities in this field, but we are keeping very high margins. So that's basically the operating part, some flesh to the operating part of our P&L, but there is one more item or one more factor which has an influence on the operating part of Sobi's business, and that's the currency exposure. We are a SEK company. We report in Swedish crowns. However, only 5% of our revenues are in SEK, which is otherwise dominated by, in particular, euro, but also more and more U.S. dollars. On the COGS side, it is slightly different with more larger share, 19% SEK out of the COGS space, because after all, we have a factory in Sweden. But on the OpEx side, SEK is actually the largest currency in our P&L. That is, of course, because of the magnitude of our activities in Sweden.
This means that if we make a simple sensitivity analysis, we use more or less the guidance, the midpoint of our guidance for 2019, and we have a 10% change in the Swedish crown compared to all other currencies. That would give an impact on revenue of about 9%. And more or less rounded numbers, SEK 1.3 billion on the 2019 basis. In EBITDA, the impact is as much as SEK 700 million because of the mix of revenues and costs. And that's actually 13% about on a rounded 2019 number. Yes, there is currency fluctuations which have an impact on our P&L. Further down the P&L, tax. What about taxes, Sobi? Well, we have a fairly stable position with 22%-23% effective tax rate in the company.
We are very dependent on the Swedish tax rates because of the magnitude of our activities and the magnitude of assets residing in Sweden. This is also why we saw a reduction of the ETR in Q1, which was influenced then by the reduction in the Swedish tax rates. Now, we move, I shouldn't say move, but we establish ourselves more and more outside of Sweden, the U.S., Switzerland. However, we do not see a short-term major impact on our tax rate going forward, and maybe I should also add that paid tax is expected to be lower than the effective tax rate. A few words about cash flow in the company. We have a very stable cash generation. We have a cash conversion over EBITDA of about 50%-60% on a rolling basis. We expect that to continue. We don't expect that to be any less.
However, because of the seasonality of Synagis, we now will see also a seasonality in our cash flows, and that means that we will expect an expansion of working capital in Q4 in particular for the RSV season, but we will also see a reduction in working capital and improved cash flow in Q2 when the season is over, so a continued very strong cash flow is the backbone of our company, and that leads me into financing and leverage of the company. We now have debt in the company. We had net cash for quite some time, but now we have a net debt of about SEK 5.6 billion. To the left is our debt portfolio. We have plenty of undrawn facilities currently, about SEK 4 billion, and we have a very balanced maturity structure on these facilities.
The SEK 5.6 billion of net debt corresponds to a pro forma leverage of about one, which is really not a lot of debt for a company like us with strong cash flows, and this strong cash flows obviously makes the debt decrease rapidly, almost as we speak. This creates, of course, a considerable debt capacity for further M&A, and of course, it's going to be the M&A which will drive the funding because without considerable M&A, we don't need to borrow any money with these cash flows. But of course, that is part of the strategy that it would happen, and we are very comfortable to lever up to levels of about 3-4 times EBITDA. In summary, as you've understood, we are building new pillars of growth.
We made important steps into immunology, and that will lead to continuous, strong, and also very balanced growth across therapeutic areas and geographies as we move forward. We have a very strong ongoing trading gross margin. We maintain a very strong overall profitability in the company despite the focused investments that we have in our growth areas. And as you've seen, we have a low leverage and continued strong cash generation. This creates a lot of headroom for M&A. So in conclusion, we feel that we are financially very well equipped to take Sobi into a very exciting future. Thank you.
I would like to introduce Phil Wood, Head of Hemophilia, and Armin Reininger, Head of Medical and Scientific Affairs.
Thank you. Good afternoon, everybody.
Good afternoon.
Thank you for joining the session with my colleague, Armin.
Thank you, Phil.
We thought we'd start off by just talking a little bit about what actually is hemophilia.
Get this to go. Which way do we go? That way. Hemophilia is a chronic disease. There are around 400,000 people on a global scale who suffer hemophilia, but around only 100,000 to 125,000 are actually treated. It's a condition that's lifelong. As soon as somebody is born, it's a genetic condition, so people suffer throughout their lives. They suffer significant physical and psychosocial disability as a consequence of the disease.
Thank you very much, Phil. If you look a little bit more in detail, and I will not bother you with a physiology lecture here, but if you look at all of us, we do have in our blood clotting factors. If we cut our finger, the bleed will stop within a few minutes.
That same system, a very refined system that has evolved over hundreds of millions of years, is also present in hemophilia patients. But if you look at the clotting factors, they work like a cascade. They circulate in the bloodstream as inactive proteins, enzymes, and once they become activated, they will activate at the step below. And in the usual way, it works like this. There is an injury to the vessel wall, the clotting cascade is activated, and it goes all the way through until a plug seals the leak. That plug is fibrin. If you think of the same thing in hemophilia patients, they have the same system, but you see here a gap, and that is the missing clotting factor, either clotting Factor VIII or IX. And if you do the same thing, that missing clotting factor makes the bleed continue endlessly.
This is why in hemophilia patients, there is a risk that those patients literally could even die from a very small injury that none of us would even notice big time, but for hemophilia patients, that could even become life-threatening. Let me translate that very simplistic approach here of how the mode of action is into some clinical aspects. What you see here is, on one hand, the acute hemophilia bleed, and on the other hand, you see from that bleed the more long-term effect and outcome of it. We all know, and Dan surely can tell you later on also some more aspects if you have questions from his daily practice, what we know is that this can become a very crippling disease.
So on the right-hand side, or for you on the left-hand side, you see an acute bleed into a knee, a joint bleed, hemarthrosis, and that bleed in all of us would resolve easily. In hemophilia patients, one or two of those bleeds could literally already lead to what you see on the right-hand side. So it's a very different mode of action in those patients, and it seems that they have peculiarities that we do not still fully understand. The bleed can also be not only in the joint, where in most cases the bleed happens, it can be into the muscle, it can be into the soft tissue, or it could even be into the brain, and there it becomes very quickly very life-threatening. So translate that into the long-term effects.
You see two knees in this case that have experienced maybe only a few of those acute bleeds on the other side, and they then literally damage the joint to the degree that it becomes arthropathy, literally a damaged joint through the way of inflammation, arthritis. Then the muscles, because the joint doesn't have its full range of motion, the muscles contract, which is what you see here. Then the result is chronic pain. The muscles become atrophic. They are not used enough, so they become less and less and weaker. Then there is a compression on the structures built into that, which is nerves, blood vessels, and then there's even neurological damage or impairment. So even the nerves can get impairment from that. All of that can come from very few bleeds.
Then you ask yourself, well, isn't that already resolved in our modern world where we have the means of prophylaxis?
We certainly think so, but we wanted to dig into this a little bit more. Talking to patients, listening to their stories, we decided that it was worth investing in a true deep ethnographic study, which we carried out last year, talking to more than 50 people with hemophilia and their carers and their whole families, talking to treaters, in all, over 500 hours of interviews and following these people through their daily lives, living with them in their homes and work and school. What we found actually was really interesting because superficially, people say they're fine. They say their children are fine. They live a normal life. It's fine. He has his treatment. He goes to school. I take my treatment. I go to work.
It sounds great. It sounds normal. But actually, when you really dig into it, what happens, if that'll change, is day by day, people change their lives to reflect their treatment. They change their lives to reflect their fear of bleeding because they fear that their treatment will not give them the cover that they need to be able to live their lives in a normal way. They have days when they feel well. They have days when they feel worried, and that has a long-term consequence as well. It means they make trade-offs about what they do on a day-to-day basis. It means they trade off activity versus non-activity versus playing football or standing on the sidelines, holding their child and feeding them or giving them to their partner to look after the child. It has significant consequences for today.
It also has significant consequences for tomorrow because people make those trade-offs worrying about tomorrow, worrying about where their lives will go based on the current standard of care.
What we found with this ethnographic research is something that was really not known in the community. There is a huge discrepancy between what the physicians think and perceive as the reality and the perceived reality of the patient. You see this here in this graph. Just let me run you a little bit through the curves here. Oops, sorry. That was the wrong one. What you see here is the factor level. If a hemophilia patient and we all have levels between 50%-150%, that is the normal range of clotting Factor VIII or clotting Factor IX.
So if we think in this case, clotting Factor VIII, if this is the level that the patient has after he injects himself with the factor, then the physician knows there is a window of opportunity and the patient can do a lot of activities. He's covered. He's protected. With more and more time after the injection, the product is cleared from the organism, literally leaves the organism. It's degraded. And then there is a zone where there is a much higher risk for bleeds occurring. So the patient would not have bleeds when he is at the level of 50% or above, but the more he goes to the 1% level or even below, he will have bleeds with quite some certainty. So the physician knows these days how to interpret. The patient has a very different view on this.
The patient thinks, "On the day when I'm injecting, I can have activities. I'm safe. I feel good." The next day already, the patient is worrying it may not be enough, and in a way, it's like you fill the tank of your car. When you have filled it, you drive. Already the next day, and you have only driven 100 km, and you could even go 500 km, you feel already worried, "Is it enough?" Because you don't know. You don't know your levels to that extent. With a new means to show it, it's easier. But if you don't know, you're really worried, and this is what the patients feel here.
We've taken a long, hard look at the therapy area and revisited our vision of how we see hemophilia and how we see life as a patient, a person with hemophilia.
I'd just like to show you a short film.
How do you recognize a challenge? The answer is you don't, unless it's yours. Each and every one of us is born into this world under different circumstances with different dreams, skills, and possibilities. Yes, we are indeed different. One person's road bump is another person's mountain. And often, we turn a blind eye to our extraordinary abilities and instead let our challenges define who we are. But what happens when you let your dreams and drive dictate what is possible? What happens when you not only recognize your rare strength, but release it? Your life is yours. Yours to explore, yours to live, yours to liberate.
So this is our new vision for how we see the world of hemophilia. And our goal is to liberate life for people with hemophilia and enable them to live beyond their hemophilia.
Thank you very much, Phil. With that vision and approach, we do really put up higher expectations for protection beyond bleeds, and I think what Dan really showed to you and explained to you, this is very much the foundation of what we have. Because why should a hemophilia patient bleed at all if the possibility is there? Isn't there something that they can do so that they really can free their lives to something never possible before? In the end, there shouldn't be any safety compromises. This is clearly the case that we are pushing very hard for, particularly with our product. Safety should not be at all in the debate. No compromises there at all, and then there are two aspects to the long-term protection. The one is from the bleeds, and you have heard that there is always a possibility.
It doesn't stop at the 3% or 5% level. Even when you go to higher levels, there's always a possibility for bleeds. When you're not trained to treat them, then as a patient, they may have that bleed. But then there is something that Dan also alluded to. There are bleeds that are not so obvious that can also happen in the long term. There is now, I think, more and more data accumulating that shows that if there is an undetected subclinical bleed, that that bleed over the course of eight years, 10 years, or even a little bit longer can lead up in 20%-25% of patients to joint damage. And the question is, so obviously, the levels that have been the target for treatment have not been enough to prevent that. So that is something that we also would like to see is tackled.
Taking all of that together as one means there should be no real burdens of hemophilia any longer for those patients, literally liberate their lives. If you then think about the clotting factor, the piece that is missing, as I showed you in the initial sketch, the one piece that is missing of that cascade, the products that we have and that's the factor in all different variabilities, short-acting and long-acting, that replacement provides the possibility to literally manage all clinical solutions. It's not that you have for a certain area or a certain way one treatment, but when it becomes a little bit more complicated, you need another treatment, another drug, like Dan alluded to, that they or do we allow our patients to have factor in addition to another product at home because we know it may happen.
I think it's a very straightforward approach if you have one product and that product covers everything. It covers everything literally from the acute bleed control, and it can be readily achieved. So when there is a bleed, you inject minutes later, you have the levels that you require. Then there's the long-term prophylaxis that can prevent the bleeds, but also the joint damage that goes along with it and also the subclinical bleed. Then there's always something that is the surgical procedure. In my practice at the clinic at the University Clinic in Munich, we have patients that had one with double knee replacement. But you do not do that replacement at levels that we just discussed that may be 5% or 10% or 20%. You need the full protection that we all have at the 100% level. Only then you can do that.
These are levels that cannot even be achieved with new technologies because they don't even target for that. So now we present you a product portfolio, if you will, with Hemophilia A and B products that we have that can cover all this. So I think that should be a piece that be at least part of the discussions. And we hear it from the clinicians all the time that they also like to have that positive approach here. If you think about the benefits of the extended half-life, if you contrast them to the short-acting half-life, and maybe just a short word, half-life stems from the point of injection, at the start of the dosing, you have your 100% of whatever concentration in the blood.
After a certain point of time, a few hours, Dan alluded to it, could be nine hours, 12 hours, even 25 hours, you have 50% of that initial dose reached. Then another half-life, again, you have half of that and so on. That means short half-life within very few days, two days maybe, the patient has no longer the factor in his system. In some other cases, extreme, after one week on EHL, on extended half-life product, you have still good protection level. On the standard half-life, you see that there is a requirement for frequent injections, sometimes wished for, but most cases, particularly in the young ones, that is not what the parents want to do, to inject their little kids every other day. Delayed start of prophylaxis that's coming out of that, then suboptimal adherence to the therapy because it's very cumbersome.
The veins are hard to find. A lot of things happen from that. And then breakthrough bleeds and subclinical bleeds as a consequence and joint disease as a more long-term consequence. On the other hand, if you go to the extended half-life factors, you do have a higher protection for longer with the same dosing frequency and same dose concentration. You have thereby improved bleed prevention. You can optimize the number of weekly injections. You have more room to wiggle and to optimize. And the consumption is also some aspect that can be optimized if under pressure. All of that supports health-related quality of life by increased protection against the bleeds. The treatment burden is reduced, and the adherence can therefore also be improved. How do we at Sobi, with our Fc fusion proteins, have that approach, I would say, almost optimized to the degree for that factor replacement?
Fc is the constant fragment of an immunoglobulin that the immune system uses. That Fc part is attached to either the clotting Factor VIII or the clotting Factor IX, and I show you here the clotting factor or Fc approach, but just from that Fc technology, there are certain benefits that come from it. One is it's a natural component, and thereby the metabolization, the clearance from the system also uses a natural pathway, then the genetic engineering of that happens in a human cell line, not any animal cell lines or other, and then it's a well-established technology to extend the half-life.
On the right-hand side, and this is for you to learn maybe if you want to look deeper into that, just to give you a very short overview, the Fc, the neonatal Fc receptor shown here, this is where on the inner lining, cell lining of every blood vessel, there are these and many other cells, these receptors, then the Fc portion binds to it. And through some internal processing, they are released again into the bloodstream. If they would not bind to that Fc receptor, that neonatal Fc receptor, they would just be degraded down to small pieces and then reused in the organism. So that re-entry into the bloodstream is one of the mechanisms that the Fc fusion really allows in a very natural way that the extension of the half-life is happening.
In the end, that results in best-in-class extended half-life products for factor VIII and for factor IX with our products Elocta and Alprolix. They do have very well-established safety and efficacy profiles, and particularly in the real-world setting, not just in the clinical program, but the real-world setting shows that that is continuing after the products came into the clinic from thousands of patients and for quite some years now. They are replacing the missing factor. And this is, again, I would say, a very strong opinion in the field still that when you have a missing factor to replace what is missing, it's the most natural approach and most straightforward approach of therapy, and particularly for hemophilia treatment. In many countries, they have become already standard of care because that is seen this is the level of what we really want to use to make the best treatment.
They are suitable, and you've heard it now several times, suitable for people with hemophilia across all age groups, across all clinical settings. By the way, the authorities do require from or have required from the ones who had those factors clearly the clinical program to show safety and efficacy, not just in the pediatric setting, but even in the adult setting, at least up to now. So there has been quite some substantially more data on these patients for those products. I really feel strongly about it because I had those patients. If you want to have someone who has to go through surgery, you need to be able to protect them. There is not a compromise that you can allow because surgery sometimes is very demanding.
And there have been other reports out that may show that other approaches with new technologies may really have quite some risk for those patients. And then the last one is create the possibilities to lead that life that you saw in the film, create a full and active life possibility, and no more worries about suboptimal protection and effectiveness of the treatment. And with that, I hand over to Phil.
So how does all this fantastic science and theory translate into actual adoption in the countries, in the markets, in the treatment centers? And we see Elocta really gaining momentum now. We see individualized therapy, intensification, and personalization really driving momentum. You'll have seen, I'm sure, our year-end results last year.
We were looking at just around full-year revenue for Elocta of just under SEK 3.3 billion, with a quarter one at just under SEK 1 billion for this year as well. So significant growth that we see there. We see reimbursement continuing throughout the region. We see continual depth and continual breadth in usage of Elocta. And it's a similar picture for Alprolix as well. We see continued impressive performance for Alprolix as the depth grows and we continue to expand in our countries as well. With a full year, 2018, of just under SEK 1 billion again, and a quarter one of just under SEK 350 million as well. So significant growth. And we expect to see that continue because when we look at our patient share, our patient share is well ahead of our cash market share.
And the way that this therapy area works is it's an accumulation of patients over time because it's lifelong therapy and people don't tend to transition to different therapies often. So our exit market share for 2018 will help to drive if we annualize that, that will create a significant increase in our share just as it stands right now. So we expect to see continued growth through the period. And what does the future bring? Well, we've heard a lot about where we are with standardized therapies, with extended half-life therapies, with alternative therapies, and the non-factor replacements. And what we see and what we believe is that even if there's compression in the overall use and the patient share in the total numbers by introduction of different therapies, that actually the category will continue to grow in itself through increased prophylaxis and increased conversion from on-demand to prophylaxis.
And what we also see and believe is that personalization, individualization, and intensification of therapy that fits so well the value proposition that our products can deliver will help us to increase our share as well. So we see the future very positive and very productive for our products in times going ahead.
So if you again think about the life cycle of, and Dan had a picture that showed the individuals, this is more what are the different challenges at those different stages. The newborn, they want to be safe, protected, no safety issues at all. Then you do want to have a very well-known safety profile and effectiveness profile. Then with more moving, the toddler, and then into the more physical activity of the adolescent or child, there comes more challenges to the clotting system.
If you then move on into some maybe trauma or other related things, you want to really have a fast bleed resolution. But at the same time, you do want to have 20-year-old ones that have not had subclinical bleeds and then end up with joint damage in their ankles and knees and that goes all the way to the full protection during surgery and all the way up to old age, maybe even joint replacements that may be needed and it may not just be due to their disease. So if you think about all of that, what is the basis for Elocta, and particularly in this case, I want to focus on Elocta, what is the basis why we are so convinced that there is so much advantage and yes, you're right.
A pharmacokinetic profile curve only shows one aspect, but I also will show you a few clinical aspects where that translates into the clinical outcome. And I think only that combination is really meaningful. But on the other hand, and I think Dan showed it nicely with the example of Bangladesh, if you do have a lab that can measure whatever, but is not really your factor level or factor level equivalent, then you may not really know where you end up. Then you're guessing and not so much basing your decisions on facts coming from the clinic. So let me run you through that quickly. So you have here in a logarithmic scale, the mean factor VIII activity, which is what determines what the factor does.
And once you have injected, and these are two examples, a short-acting and Elocta factor VIII product, this is the time, and this is how that whole product in the bloodstream after one injection gets cleared from the organism. This is happening in all of us, but we constantly reproduce the factors. And if you have to inject it, this is the usual course. Only extending that, only in quotation marks, that half-life through the Fc attachment brings at every level a much longer time where that one level goes already down while it is reached with the extended half-life at a much later stage or time. And that means with the same dose injection, you can go much longer, and you are still, and this is what is usually called area under the curve.
If you think of it in terms of shaded area under this curve here or under the other curve, this also is in a way an index number for protection. And the benefits are listed here. So you have one-third less quick clearance from the system. You have a much higher area under the curve translated into protection. You have a 1.5-fold longer half-life as well as more time until the more risky bleed levels are reached. If you now look at this and look at this in particular in that comparison throughout a week from Monday to Monday, same dosing, three times 30 units per kg body weight. The blue line shows what an EHL, Elocta, could do. And the black line shows you where the other one is going. And I think that clearly shows you also where much more protection is done here.
Higher levels, and you see here the levels even after the two days of 10%, 10%, and even after the long weekend, it's still in the 3%- 5% range. That is much more protection with it, and now I come to the clinical translation. If you look at our clinical program, the aspects here that you see, let me start with the other side here, not the prophylaxis. Although you may have thought from Dan's presentation that is already completely spread across Europe, at least, or Western world, there still is quite a substantial number of patients who have decided that they only treat themselves once they have had a bleed, which is called on-demand treatment. If you look at the mean or the median, you see it's around 20, but the range is from 15- 30.
Those patients at the upper end have bled 30 times in a year. And you think, "Well, that's not a small number for bleeds." The overall number is shown here. Then spontaneous numbers, 15, joint bleeds, 13, and spontaneous joint bleeds. Without any trauma causing the joint bleed, still in the range of nine. You think, that is again something that will for sure cause damages to the joint, will for sure have a major impact on the life of that patient. Now look what came out of our program with individualized prophylaxis. At all these dimensions, we're very close or at zero. I think that is something that is for us the standard that everyone else has to beat. We're not talking inhibitor patients now. This is non-inhibitor patients, and that is the benchmark.
That benchmark continues if you look into the long-term outcome of this because coming from our A-LONG program into the ASPIRE study, and you see here year one to four, we have had an improvement of the joint score, so the patients that had already joint damage and the scoring, the higher the scoring Dan showed it, the higher the scoring, the more they have had problems with their joints. The more the number goes down, the better the joint is, but what we have found, very surprising and never shown before with hemophilia treatment, that a damaged joint literally can improve when you score it, and this has happened and has been shown only with Elocta, and the last one, or the one before last, is the same goes now for the quality of life. Again, the same principle, minus numbers show improvement. This is the starting point.
And in all three dimensions of physical health, sports, leisure, and feeling, they have improved to the starting point. So not only there are facts and measurable aspects, but also the patients do feel it. So in the end, we feel that the Elocta represents an innovative treatment option that has demonstrated efficacy and very well-established safety profile for people with hemophilia. It's the first and only one that uses the Fc technology, as I said, natural recycling pathway, and it may even convey into other immunomodulatory aspects that we're still exploring with some studies. It has a very good long-term joint protection. We have built confidence over quite some years and quite many patients, overall eight years of clinical experience and four years of real world. And it's across all clinical settings, all age ranges.
And not to be forgotten, you can measure it easily with a very well-established, for years, very well-established test in all those clinics and practices.
So with that. Thank you. So I guess just to kind of summarize this, really. So we believe we have every opportunity to continue to grow. We believe that our value proposition is very strong. That in the future, because of all the reasons we've discussed, the outline of the treatment therapies as they stand today and tomorrow, replacement factors will remain the standard of care because of their applicability across such a wide range of applications and patient types.
We believe that there will be an evolution of the standard of care as well, that people will continue to shift from on-demand to prophylaxis, and there will be a continual need to raise the standard of care and raise the factor level for people so that they can be activated to live their lives. And ultimately, everybody who is somebody who has hemophilia is an individual. They're all different. They're physiologically different. They're emotionally different. They're physically different. And they have different needs and different expectations of life. And our goal is to enable them to liberate their lives, to live beyond their hemophilia, and to provide the treatments that enable them to do that. And we very much believe that our therapies will do that today and for the future as well. That's it.
End of that. Thank you.
Thank you.
We will have time for some questions before the coffee break. So yes.
Thank you. So you talked about growth in the prophy market from on-demand. So can you talk about looking at hemophilia A, what percent of current treatment, not just yours in general in Europe, what percent is coming from prophy versus on-demand today versus compared to about five years ago?
So I mean, that's a really good question. The evolution of prophy to on-demand now versus five years because the data is, I'm sure you know, is very hard to come by. Generally speaking, around 2/3 of the use of factor VIII is to treat people with prophylaxis. So the actual number of people is less than half who are treated with prophylaxis currently. And as you'll see from Dan's slide too, consumption continues to grow not just in the U.K., but across the board.
And that's as people are converted through from on-demand to prophylaxis. And even on prophylaxis, their consumption continues to rise as they have personalized treatment that enables them to reach those higher levels that generally correlate with activity, which also generally correlate historically with when people get bleeds. Thank you.
Yes, Peter.
It's Peter from Handelsbanken. Thank you for taking my question. Just one pass more for Henrik. Would you consider monetizing your royalty income stream from Sanofi? Thank you. Just a question.
You're on.
I think I'm on, yeah. It is not on top of our agenda. We have other means of accessing money, which have higher priority at the moment.
Okay. Christopher.
Thanks. So with the Liberate campaign, what you're really talking about is changing the standard of care. And I'm just wondering, to what extent do you need to back that up with trials?
And maybe we can get your take on that, but also Daniel's take, please.
That would be the usual approach. It has to be a trial or you don't have facts. But I think trial is always a question. Are you approaching something where you need a trial to validate a certain kind of approach? But in the end, it is also about, I mean, and when you say trial, I also think real-world phase four trials. And yes, I do believe the more you have that and not just do something and spread out news, the more you will come to that end. And this is why we also do quite a few trials in the phase four setting, continuing the experiences that we have. So we have a few lined up, yes. And particularly on the inhibitor immunomodulatory aspect, there are two running.
We also have phase IV trials that literally show the joint protection as well as other aspects that we really feed into that whole approach. We want to back that up with facts and not just talk about it. Absolutely.
We will initiate a program that gathers beyond the clinical data as well that looks right through the patient experience to correlate that with the activity with their treatment paradigm.
Is the PROPEL study from Shire something that would be kind of thing you would do? Sorry. Is the PROPEL study from Shire the kind of thing that you might do as well?
Since I have worked in that company that started that PROPEL study idea at that time, just to continue what we have thought up years ago is not the Sobi approach.
The Sobi approach is to be creative and come up with really good and new ideas and not just repeat what even us working back then have done, and definitely not just to copy what other competitors are doing. We will hopefully be able to surprise you with more creative ideas than just copying.
Okay. Thank you very much, Phil and Armin and Dan. We will now take a 15-minute coffee break, and we'll start at 3:00 P.M. again with immunology. Thank you. Welcome back, everyone. That was a very comprehensive session about hemophilia. And there were many questions. And for those of you that didn't get to ask your question, as I said in the beginning, there will be a Q&A by the end of today as well. So no worries about that. So now we're moving from hemophilia to immunology.
And by that, I want to hand over to our Head of Specialty Care and Immunology, Norbert Oppitz.
Yeah. Thank you very much. Good afternoon, everybody. Thanks for making it back from the coffee break. So I will now try to explain to you in the next 20, 25, 30 minutes what we are doing in immunology, why we believe this is important, and why this will be really a driver for our future. If you look at immunology as a scientific discipline, it covers many therapeutic areas. It is one of those areas where I believe right now a lot of breakthroughs are made. Immunological processes, inflammatory processes in the human body are linked to more and more human diseases, to more and more pathologies. So this is something that is vibrating with science. This is something that is vibrating with innovation.
And a company like Sobi, focusing on rare diseases with a high degree of medicalization and with our capability to clinically differentiate products, we want to be there. We have to be there. It obviously does also not hurt that this is not only science-driven. It is also financially very, very attractive. It is fast-growing. It will be beyond 100 billion by a general estimation in about three-to-four years from now. And it is at the heart of what we do. We have, obviously, with Kineret, a very important product. We will look into that in a while. And we have two new products. Guido hinted already to them, emapalumab and Synagis. And they really provide us with an excellent platform in the area of immunology.
So if we look at the growth of a market, let's say not expressed by number of products or clinical studies or patients, but simply monetary growth, we are talking here about a consolidated growth of 8%, a CAGR of 8%. This makes it one of the most dynamic and one of the most interesting therapeutic areas. And we can see that the projections in the future are really optimistic. This is driven by science, and we will take our molecules and our capabilities to where science leads us. Right now, we are there with three strong assets. We have Synagis. I will start with Synagis in my presentation right now. We have Gamifant, and we have Kineret. Now, when we looked at Guido's explanation of Synagis, this got a little bit technical.
We were talking about how sales developed, how units were shifted, how distribution changed, modified sales, etc., etc. And this is important. This helps us with some understanding of numbers. But these numbers are just a picture of a movie. And I would like to explain to you a little bit what is this all about. Why would I expect you to believe that Sobi takes on Synagis and will be more successful than the predecessor? What is Synagis about? What is now RSV? So Synagis is a product that is an immunoprophylaxis. It is directed to RSV, potential RSV patients, because obviously, the idea of a prophylaxis is to avoid the infection. And this is basically directed at preterm babies. But this is just where the current reimbursement sits.
I mean, from a medical point of view, many, many non-preterm babies, children, also children with heart diseases, lung diseases, but also elderly patients can acquire the virus and can get this infection. And what sounds so innocent, like just a viral infection, is causing 57,000 hospitalizations every year in the U.S. It is the single largest reason of infant hospitalization. These babies come to the hospital, or these infants come to the hospital very sick. They normally, to a large percentage, go into intensive care units. It's a very tough treatment. We come to that. On a global basis, it is one of the leading causes of death, especially in countries that do not have the capabilities, first of all, to prevent, but then also to successfully treat. So it is a very, very important, a very dramatic diagnosis.
It really merits to have the maximum of protection to these children, to these babies that a society can afford. It usually ends up with a typical respiratory infection very dramatically. It goes down, as you can see here, into bronchiolitis, pneumonia. This very often then ends up with very invasive mechanical ventilation to keep them breathing. There has been a study published at the end of last month that has observed the development of hospitalizations and outcomes of the seasons of 2014-2015 and 2015-2016. It was conducted in 64 hospitals in the U.S. of A. It was 1,378 babies who were hospitalized in these clinics over these two seasons. 45% of them made it to ICU, to intensive care treatment. Nearly 20% had received mechanical ventilation assistance, which is very invasive. Two of them passed away. Synagis is a protection. It is not a new product.
It is proven. It was approved in 1998. It has actually protected 3 million babies from this fate to acquire this virus and the disease. It is eligible currently for treatment limited to premature babies or children with heart or lung disease. This is something we come back to because I believe a society can do better, and we can do better. And atypically, it is not one shot. It is also absolutely not a vaccine. It's an immunoprophylaxis. It requires five injections. And these injections can actually be far away from one another because this is a seasonal phenomenon of a virus. It starts usually in fall, and it ends then in autumn. So it might very well be that a preterm baby is protected at the end of one season and then has to continue with the protection in the first months of the following season.
So it is not always linear. It is complicated. But this is a fantastic and a proven product, and this is a proven prevention of a very dramatic disease. We did not only acquire a product. Fortunately, and Guido hinted to it, we acquired the team who drove it. And these are people that fit very much into our culture. At Sobi, we are focused on patients. You cannot not focus on patients if you're working in rare diseases. You're always close. The individuals who are driving this product really have very little patients close at heart. Right from the meetings when we were still in diligence and listening, it was absolutely fascinating to hear them refer to their babies, their patients. They are doing the maximum.
When Sobi offered the choice, when we offered them the choice to go with us and come with us and join the team, as Guido said, I mean, 135 out of 135 accepted. Obviously, that says a lot that I like very much about Sobi, but this says also a lot about the people who joined. We got the right people. We've done a very fast integration. There have been the usual work streams managed very well. The U.S. team did fantastic. There have been transition agreements all about handing over with customers, with distribution, etc. All on track, all ticked, a seamless integration. On the back office side, and this is one of the differences why I believe that we will do better than the previous owners, we have put in 35 people who will basically now support the sales force.
We have put more resources and more input to this product again because, obviously, for us at Sobi, this is 100%. This is now the topic, whereas the former owners had it a little bit as a product at the end of a life cycle and did not care so much. But I think that our capabilities and our desire to drive this and the professionality of those 135 individuals who joined us will really make a huge difference. And this difference is very important. What is happening today? Where are we today with Synagis in the U.S.? If we look at this, we have about 63,000 patients who qualify to be in label. So this is the total number of adequate either preterm babies or babies with a precondition in heart or lung that would be reimbursed and should be treated and protected with Synagis.
There is, however, a funnel, and there are different steps the patients have to come by in order to be successfully treated. And at the end of the day, where we are today out of these 63,000, actually 18,000 patients receive the complete and adequate treatment, all five cycles, all done, full protection. We believe that we have to work on to focus on the following topics. Number one, there are still physicians out there, unbelievably, but it's the truth. They're not familiar with the guidelines. There's not yet the full consciousness about RSV that we believe should be there. So that means there is a certain lack of information that has to be filled.
And then again, there's also on the side of caregivers in general, there's a little bit still of lack of information that we need to complete, that we need to provide, that we need to carry out to them. Then, on the other side, to get them, now some get the prescription. Now we need to go to the first dose. We have access challenges. Payers are obviously not always happy in following up. There are obstacles. It's sometimes difficult to fill in the forms, etc., etc. And again, it's not a one-shot treatment. This is more of a process. So there are some administrative and technical hurdles, and they sometimes lead to a certain attrition. The payer approval process is sometimes very cumbersome.
And sometimes, although a physician understands the treatment and wants it employed because he understands very well the benefit it brings, the physician's office is a little bit overwhelmed and cannot adequately take the patients by the hand and lead them through the corresponding administrative processes. And then later on, the phenomena I described, especially those subsequent doses that do not come immediately, but after kind of a break or a summer break, sometimes are not really followed up, are not given. So basically, all these three different elements lead to 18,000 fully adequately treated patients, where that should be much closer to this number. We have roughly 45,000 patients who do not make it to full treatment. Now, we are focusing exactly on these three points. So what are we going to do now in our first year at Sobi with Synagis?
First of all, the first element of the funnel, we have really to make sure that all stakeholders are educated on the need for protection, and that means basically here talking to physicians, caregivers to hospitals, but also try to help with the administrative processes, so here we will directly attack the first element, the first curve of attrition where we lose patients. The second element is obviously here. We need recent data, and again, this data is hot. The study was published, I think, 30th of April. It's the Sentinel study. You can find it on the World Wide Web. We have now really data about the number of hospitalizations, the impact of hospitalizations, the burden to the patient, the burden ultimately also to the payer, the burden to society. This is an underestimated and not very well understood problem.
And we need now to work and to make sure that it gets the advocacy that it deserves. And last but not least, it's not only now about physicians and payers, but we really need also to engage external stakeholders. And that again means we have to utilize key KOLs, key opinion leaders, professional trained physicians to make sure that we help a broader group of stakeholders to understand what this means, why it is important, and what we can do about it. And this ultimately should lead to having the key audiences aligned to shape the thinking process to help everybody to identify, to understand this need for treatments. And this will drive Synagis. Now we come to the other very exciting new kid on the block, Gamifant. Gamifant has been launched literally in the last days of the last year.
It addresses a very important and highly unmet medical need. We are talking about HLH, hemophagocytic lymphohistiocytosis. HLH is good enough. It's a complicated word. It's an even more complicated disease. Or actually, this is a syndrome. HLH, as innocent as the three-letter sound, is something that wreaks absolute havoc on the lives of patients and families. There are patient advocacy groups in the U.S. I had the opportunity to talk to a mother who lost her two children to this disease and who started together with her husband a patient advocacy group, which is absolutely admirable.
And the moment when I understood what HLH means was when she said, explaining her way through the hospitals and physicians to the specialist centers, that at one moment she realized when all they were afraid of was that her child has cancer, they realized at the moment that cancer actually turned out to be the less worse option. And this was the moment when I heard these words from the mouth of the mother where I started really to click and to understand the disease. HLH is a killer. There are two forms of it. And Milan will go a little bit deeper into the scientific side. What I would like you to take away here is it is something that starts very innocent with a fever, with many of the symptoms children have. There are two different types of HLH.
Both of them develop very rapidly into life-threatening conditions. We have a primary and a secondary HLH. I come to that in a moment. We expect roughly to have 200 patients per year in the U.S. in the year of primary HLH and a much larger group of about 4,000+ 4,200+ patients in secondary HLH. What's the difference? Primary HLH has an underlying genetic condition within the patient. So it is a patient that is preconditioned will most likely develop it. It has to be confirmed by genetic tests. These tests take quite a while. So once a patient is received and treated, treatment must be initiated very, very quick. Most of the patients, when they are presented, do not have the time to wait for a three or whatever week outcome of a genetic test.
The good news for the first group is primary HLH, ultimately, if the treatment is successful, the patient can be treated out of a current dramatic condition and stabilized. They can get a stem cell transplant, which, if it is successful and it goes well, is curative. But it is a long way to there, and it is a very, very long way to treat these children back to a form where they would be eligible because, again, this is a very dramatic disease. This can be suspected even without genetic confirmation if there's a family history, an affected sibling, or if there are other cases around the family where children died unexpectedly. It's a little bit finding out, good old Sherlock Holmes research. But many times, this is how actually these patients are diagnosed. Should not be underestimated. Ultimate confirmation, genetic testing.
Obviously, these patients are more frequently infants or children. This is where a form of HLH, primary HLH, where we have received as the first and only drug market authorization in the U.S., where we have launched emapalumab under the brand of Gamifant. This is now available in the U.S. market since December of last year. There's another type of HLH, secondary HLH. It is not less dramatic, but it has a different origin. It is acquired. It can be acquired because of underlying malignancy conditions of autoimmune conditions or if several infections. Basically, there's a variety of causes. These patients, more often than not, are then not children. They are adults. It comes later in life. Obviously, they would not potentially benefit from a post, let's say, treatment stem cell transplant.
Here, the goal is again to treat the patient out of a situation and to get the patient stable again to diagnose and to treat the underlying disease. So we have now the disease. We have a product. What are we going to do with it? It is ultra early days. It has a couple of weeks literally in the market. We had a very promising patient uptake. Actually, we managed, and some people did some miracles. It was literally over Christmas that we got a product to the first patient into the US right after approval. This turned out to be very fortunate for the patient to receive treatment because it was really a very good start. There's a lot of questions. There are patients coming on. There's a lot of inquiries from physicians. We are at congresses. This is something that definitely will shape the treatment of HLH.
It is, however, not only the classical rollout of a new drug. What we have to do here is we have to execute on the launch, and that's not only talking about emapalumab. It is talking about the role of interferon gamma in HLH. Why should it be treated? It's the entire concept. Again, it is ultra medicalized. It's very scientific, and it is really a fantastic opportunity to save human life. Beyond the U.S., we prepare to launch in Europe, so we expect a market authorization at the end of this year, 2019. We are working very heavily with large groups of getting there again in primary HLH, then we think about geographic expansion, Middle East, Japan, and then some Canada and Switzerland because there are certain, let's say, fast-track opportunities to accelerate a little bit for orphan disease drug, and this is obviously ultra-rare disease.
So we are working on several fronts to do justice. And the most important thing we will see in the next slide why. We also now are going to expand the label. And that means we go into secondary HLH groups, both pediatric and adult. And some things that turned out in clinical studies, and Milan will talk to that also, give us very good reasons to believe that it might be a good idea to look at the potential use of emapalumab and at the potential interferon gamma suppression in patients who have a risk of graft failure. So again, all this is obviously designed to, first of all, do justice to this currently small today group of patients in the U.S. But then again, as we roll out the clinical studies, one is ongoing.
The other is right now submitted to FDA and should also be online, absolutely sure this year. We are now progressively scientifically working our way into this patients group, make sure that this will be available as soon as possible to secondary HLH patients, and then basically repeat this over with geographies. Again, there's a lot of science behind this, and studies will unlock the opportunities. So this is really early days, but a fantastic future. Really, I have to say I'm proud to be part of this because in our industry, we do not have so often the opportunity to really touch something with our own hands that so dramatically transforms human life. From there now to our little bit more older product, Kineret, anakinra. This is a fantastic story. Kineret actually was originally developed in RA, and it's basically an IL-1 inhibition.
It has a fantastic growth story, both in Europe and the U.S. It is here sitting in several indications in our CAPS and Still's in Europe and in our NOMID in the U.S. However, this is one of the products that clearly underlines the dynamic of where science is leading us. Because these indications here are more or less already saturated, but if we look into the development of what physicians, scientists, clinicians find out about the benefits and the potential of Kineret, it is absolutely mind-boggling. As we stand here today, there are more than 1,300 publications about Kineret, and they come in really in an astonishing rate, and I give you some examples about the areas we cover. We are talking about roughly 140 different indications where Kineret has been actively investigated, put into clinical trials by clinicians, not initiated by Sobi.
This is something absolutely fantastic, and it clearly tells us there's so much more to do here. With this build-up, there are some indications. If you think about where we started with RA, it does not immediately jump to mind. There are now investigator studies in IRP, idiopathic recurrent pericarditis, which is basically the sac where the human heart sits in is getting inflamed. It is a very painful and critical condition. Right now, ultimately with several different treatment schemes, many times the patient ends up with this actually being removed. It is very dramatic. It seems that Kineret is going to work. We are currently looking at this. I'm sorry, we are currently looking at this and try to find out how we can now find out if we can put this to use or not. There's other clinical data, PDAC, pancreatic ductal adenocarcinoma.
This is a metastatic cancer with an absolutely poor prognosis. This is one of the things no patient on the planet wants to hear from his physician because when these patients are diagnosed, usually they are thinking more about months than anything else, for sure not in years. There have been investigator outside studies not driven by Sobi that have shown that this has really moved the overall survival against standard of therapy. And again, we are looking at this right now, and we are in dialogue with these physicians, and we try to find out if we can now look at this from another point of view and maybe deepen that or partner it. And again, another, we all heard about CAR T treatment, the T-cell therapies.
This is an oncologic treatment developed by other companies, basically modifying T-cells and bringing them, after having them programmed against specific tumor surfaces, back into the human body. It's a fantastic idea. It works also well. It comes with a disadvantage. It leads to, in some patients, to very huge, it's like a super inflammatory reaction. And this obviously is not good for the patient. Many times it gets into neurotoxicity. And as a result, the patients then have to interrupt the treatment and cannot complete the treatment. And it seems from what we've learned and we're currently also investigators looking at this that Kineret can mitigate to a certain extent these episodes, and maybe Kineret could be helpful if we have a closer look in getting this treatment to be successful without having the patients being forced to abandon.
So even for a product like Kineret that has a long term and a very successful history, this is not the end of the road. Again, there's a lot of science. There's a lot of clinical knowledge. We will look at this. We will take that. We are now not yet actively pursuing this, but these are the directions we are looking at right now. And I can tell you Kineret has not yet seen the end of the road, quite the opposite. I'm sure that we will be also surprised by the therapeutic contributions this drug can make. Again, it's very good to have it. It gives us a lot of good connections of knowledge, of capabilities in inflammation.
So it somehow closes the circle why Sobi should be there, why inflammation is important, what we bring to all this, but also what, thank God, many physicians, many clinicians are willing to share with us. So basically, what I want you to take away today is we believe that inflammation is a key therapeutic area for Sobi's future. We believe that with Synagis, we can really get a lot more out of this product and do it more justice than the former owners have been able to. We do believe that with Gamifant, we have a transformation for the treatment of HLH patients. And we do believe that even with the comparably older Kineret, we have a brilliant future. That was my last slide. Thank you very much.
So we have some time for questions to Norbert. Yes, Richard.
Yeah, I've got a question on Synagis. If you read the guideline change when the patient population that was eligible was restricted, one of the reasons for that was the relatively modest real-world efficacy, which when you look at the clinical trials, there was a, I think, 50% reduction in hospitalizations. But can you talk about what you can do to address that perception and potentially change guidelines, whether it be with Synagis or with the follow-on product? And would that 8897 potentially have improved efficacy to address that concern of the guideline within the guidelines?
Yeah, I think that's a very good question because this is the very heart of it. There is always the conflict about what is prevention. Do I really need prevention? What do I prevent? And this is something that goes through all pharmaceutical treatments. Right now, especially in the U.S., we have a very lively debate on vaccines, for example. This is not a vaccine, but it is a similar approach. It's prevention. So what we do actually and what we are doing actively by getting out this study and the data, we are compiling hard data showing real-world, real-life patient numbers. Because these, it's just in the 46 hospitals, these 1,378 patients, they were avoidable. And to have 45% of them in ICU and to have them on a mechanical ventilation, which is a very tough intubation, it comes at a huge cost.
It is not only the human burden. It is also not good for the system. It's not good for the health system. So the question is here, what can we avoid to happen and what does it mean? What is the overall benefit? And this is what we are working on. It is the data. I mean, the efficacy and tolerability of the product have been proven. It's three million patients talking to it. But the question is here, what is a society or a payer willing to accept? So what we have to do here, we have to put a second debate on top of a pure clinical debate, which is pharmacoeconomics, which is why would I, as a society, be interested in protecting these children for a variety of reasons.
Then there is something else that we also have learned a lot about as a company now with Gamifant. There is the power of patient advocacy groups. There is a very strong culture in the U.S. for this kind of causes where I believe we can get additional share of voice and we will get better access ultimately to the deciding Gremium who say yes or no in or out. And yes, we will actively try and pursue to systematically enlarge eligible patients. We want to get the largest group possible protected. But even so, under today's label, you have seen that basically from the 63,000 eligible, we somehow end up with 18,000. So if we just close our eyes and look at this funnel, we have to realize not half of today's eligible patients are really treated through.
So even this is a potential that has never been realized. And this is also what we are working on. So there are several streams of activity, and there are several strategies basically all going to the same goal: increase the number of protected patients, make sure that they are protected the right way, see them through the complete treatment cycle. And this will be good for the patients. It will be good for the society, and it will be good for Synagis.
Maybe not just to add one thing here, that we will submit to the relevant authorities where basically now we do the inverse logic and say, "What has happened after you have changed the guidelines?" And how many more patients have been hospitalized? And those data we were going to make available for the authorities to have another look at and basically reassess the effectiveness. And I think this is what we're currently doing. So it's a bit premature to provide you with data, but at the right point, we will obviously make those data available.
Okay. And then another question on Gamifant. The dosing is obviously weight-based, and it's currently priced on the per gram basis, which is obviously a limitation to off-label use in the adult setting because it gets very expensive. So can you talk about how you expect to manage that from a pricing perspective? Is it just potentially to cap the overall cost per patient, or what would be the strategy there?
First of all, also I think this is very important. The pricing that we have is the pricing for what the patient group product has been developed into. That's predominantly infants, primary HLH. We have no interest as a company. We do not want to promote off-label use. This is just something that is hitting us because the drug has received a lot of interest. We are currently working in clinical studies. We are also having different kinds of compassionate use and maybe expanded use. But then again, we are very clearly sticking to our label. Patients who are not primary or secondary, they can either enter into clinical studies if they are eligible or otherwise. As a company, we do not have a role here.
Having said that, yes, of course, we are also observing this, and we also did the math, and we are right now actively working on several scenarios and strategies to find out how to mitigate that. I cannot yet tell you what the final model is looking like, but we are looking at this very actively, and until we have indication, we will also have an answer, so this is definitely in the works.
Yeah, so basically, what we will very likely work is that we just say this is a treatment for, let's say, per patient, irregardless, but as Norbert said, we are not encouraging off-label use, but this is a very debilitating disease in any case, and we'll have to figure out the right formula, and this is what we're currently doing.
Thank you.
Yes. Sorry.
Another question on Gamifant, if I may. When do we expect to see data from the ongoing trials in the pediatric and adult settings? And when do you expect to see meaningful sales from secondary HLH?
I mean, the trial is yet submitted for a secondary HLH. So I mean, this will take us at least about two years until we have it completely through. And I mean, we have basically shown here the timelines. I mean, we have obviously right now the focus on primary. And then once the trial gets through, this population will also get broader. But we will also, in the meantime, expand primary HLH beyond the U.S. So you will see a high frequency of movements that will enlarge the opportunity for the product. It's the combination not only of different indications, but also of geographies. And so I believe it will not really be a big bang. What you will see is a comparably steady growth that then jumps from time to time.
But I think we will have. It depends how you define meaningful, but I'm very, very sure that we will see quite meaningful sales, so.
Okay. Thank you, Norbert. I think we need to move on now. And if you have more questions, you will be able to ask them by the end of today. So that will.
Thank you very much.
Thank you. We will then move on to our pipeline. Let me introduce you to our Head of R&D and CMO, Milan Zdravkovic. Welcome.
Thank you very much, Linda. It's great to be here today. My name is Milan Zdravkovic. As Linda said, I'm head of R&D and Chief Medical Officer at Sobi. So what I will be discussing today is the R&D pipeline. And what I in particular will be focusing on is hemophilia BIVV001. I will say some words about immunology, emapalumab, MEDI 8897. And then I'll end up talking about specialty care and 003. Now, this slide illustrates our R&D pipeline and the significant value that we have achieved to build into the pipeline in the past 12 months.
In particular, I would like to highlight the very encouraging data with BIVV001 that was recently released, the licensing agreement with emapalumab and Novimmune, and the subsequent approval of emapalumab for primary HLH in the U.S., the agreement with Synagis, and the acquisition of Synagis from AstraZeneca with the subsequent participation in 50% of the U.S. rights for 8897, and then finally the entrance of 003 into humans. Now, if we start with BIVV001. So this slide gives a perspective on the half-life conundrum within factor VIII therapy in hemophilia A. So on the one hand, von Willebrand factor protects the factor VIII molecule against too rapid degradation. On the other hand, once factor VIII is bound to von Willebrand factor, the von Willebrand factor mediated clearance becomes a dominant factor determining the half-life. And it's in this light that you should see the molecular format of BIVV001.
It has basically been designed to overcome this von Willebrand factor mediated half-life ceiling. On this slide, I'm illustrating the molecular format of BIVV001. It's based on the similarity to the Elocta molecule. Then two natural repeat amino acid sequences have been added, the so-called XTEN moieties to further prolong the half-life. And in addition, parts of the von Willebrand factor have been covalently added to the molecule. The pharmacological activity has been retained. Upon thrombin activation, what happens is that these moieties get cleaved off, and essentially we are left with a molecule that is similar to Elocta. The first clinical data were recently reported. Here I'm sharing data at what I would call the clinically relevant dose of 65 units per kg in the first two patients treated IV single dose with BIVV001, and then in comparison to recombinant human factor VIII.
I think the first thing you can appreciate is that the half-life is to the tune of around two days now. So the molecular format has indeed been able to prolong the half-life. And when you look at the low level after approximately one week, you see a trough level to the tune of around 18%. I think this is extraordinarily remarkable, and I think it lends very well into the discussion with Dan and Armin and Phil around how can we do more for patients and how can we help them liberate life. I think there are three things that are important when you view this profile, looking from when dosing was initiated on the left-hand side and moving towards the seven-day point. So patients have the normal range for factor VIII activity is between 50% and 150%.
During the first three days following the single dose, these patients with hemophilia A are in the normal range. Up to around five days, we see a factor VIII activity of around 40%, which is just on the cusp of the upper level of mild hemophilia. Basically, throughout the first five days, these patients essentially are similar to the phenotype of mild hemophilia. For the final two days, assuming a dosing interval of once weekly, these patients would come well within the range of mild hemophilia. We think that BIVV001 has a tremendous potential. We think it has a tremendous potential to add protection to patients. We think it has a tremendous potential also to allow patients to live a normal life. If we move on to emapalumab or Gamifant, as Norbert alluded to, emapalumab is approved for primary HLH in the U.S.
We received the approval in the U.S. late last year. A few words about the disease. So HLH, or hemophagocytic lymphohistiocytosis, is a disease characterized by a hyperinflammatory state where interferon gamma is one of the fundamental culprits. This hyperactivation of the immune system leads essentially to the immune cells targeting the body's own cells. So patients experience fever. Patients experience low white blood cell counts. They experience low thrombocytes. They experience low red blood cell counts. There's increased spleen and liver size. There is a very significant CNS component to this disease. There's a rash. And unless treated, this disease is associated with very significant morbidity and mortality. Now, around more than 25 years ago, actually out of Karolinska Hospital and Jan-Inge Henter's group, the first data started to emerge supporting a role of increased cytokine levels being pathogenic for the disease.
Here I'm showing data with interferon gamma in patients with primary HLH that have active disease in comparison to patients that did not have active disease. You can clearly appreciate that in this patient population of primary HLH patients, there is an increase in interferon gamma levels. More recently, part of the molecular mechanism behind the pathogenesis of primary HLH has been elucidated. Essentially, during normal immune system surveillance of infected cells, the infected cell will start expressing certain proteins that will be detected by the immune cells. The immune cells will be activated. This includes interferon gamma, macrophage activation. The cell will be killed. The cell will be lysed and engulfed, and the immune activation will cease. When the infected cell is cleared, the immune activation stops. In primary HLH, what happens is that this negative feedback loop doesn't work.
So essentially, because the immune cell cannot kill the infected cell, there is a constitutive synthesis of interferon gamma and activation of the immune system. And this is what causes the symptoms of the disease. Now, emapalumab is a human antibody against interferon gamma. Interferon gamma binds to the interferon gamma receptor. And when it binds to the two forms of the receptor, there's a dimerization and downstream signaling starts. Emapalumab binds both to the soluble and the bound form of interferon gamma and thereby actually prevents the activities of interferon gamma. This slide shows data from the pivotal phase III trial that led to the approval of emapalumab for primary HLH in the U.S. So based on criteria that were essentially modeled based on the HLH disease criteria, following treatment with emapalumab, approximately two-thirds of patients responded to emapalumab treatment.
Now, not only that, but in the majority of patients, these patients had actually failed conventional therapy, and here we also saw quite dramatic effects of emapalumab to the tune of around 63% of patients responding. This actually also translated into improved survival, so when we look at the full population of patients, approximately 70% of the patients survived for a period of 12 months. If we then look at the subgroup of patients that had to undergo hematopoietic stem cell transplantation, which is curative for primary HLH, what we saw was in that subgroup, around 90% of patients survived. We think these data are quite remarkable. This also lends merit to the hypothesis that both Guido and Norbert suggested that potentially interferon gamma has a permissive effect, that somehow interferon gamma protects the graft from being rejected, and this is something we want to study in more detail.
I have some slides where I will discuss this. As we have discussed previously, in 2019, we will continue investments into clinical studies with emapalumab. We will complete the study in secondary HLH in patients with SLE developing macrophage activation syndrome, in particular in patients failing steroid therapy. We will initiate a study in adult patients with secondary HLH, both malignancy and non-malignancy induced. Finally, we are working on a phase II study to see if we can come closer to the effects of interferon gamma blockade in patients undergoing hematopoietic stem cell transplantation to see whether there is a beneficial effect of emapalumab in that setting. The first study I want to discuss in a bit more detail is the secondary HLH study in children with SLE developing macrophage activation syndrome. The study is well underway. The first six patients have been enrolled.
We plan to enroll a total of six patients. I think to the question that was just asked, we plan to share scientific data from this study during 2019 at a coming scientific meeting from the first six patients. On the right-hand side, you can see some of the supportive evidence that actually led Novimmune originally to initiate this study, showing that there is an interferon gamma signature that is increased in patients that have macrophage activation syndrome. If we move on to the next study, which is in adult patients with secondary HLH, both malignancy and non-malignancy induced, then there is observational data that supports an interferon gamma signature both in adult patients with malignancy, but just as well also in adult patients that do not have malignancy, and we plan to initiate this study during this year. We initially plan to enroll 10 patients in each cohort.
Based on that, we will adaptively decide how many patients we would need. The final study I want to discuss is the preemptive treatment study in patients undergoing hematopoietic stem cell transplantation and the role of interferon gamma. On this slide, I'm showing you increased interferon gamma levels in patients that have graft failure in comparison to a control group. There are two important messages on this slide. First message is that it seems like an increase in interferon gamma or the interferon gamma signature can be used diagnostically to find patients that actually have graft failure. The second point I want to make with this slide is that this also suggests that blocking the interferon gamma secretion could have an effect on actually preventing graft failure from occurring. This study is something that we want to initiate and where we are currently in the planning phase.
If I then move on to immunology and 8897. 8897 is a human antibody. It targets the fusion protein of the RSV virus. There is both in vitro evidence and also preclinical evidence that 8897 has an increased potency in comparison to palivizumab or Synagis. In addition to that, the Fc end of the molecule has been modified utilizing the Fc neonatal receptor recycling mechanism and thereby prolonging the half-life of the molecule. I'll share some of the data from clinical studies supporting that this molecule may be given once during an RSV season in contrast to Synagis that has to be given once every month. In the U.S., it has received fast-track designation and breakthrough designation. Very recently, the top-line results from the phase II- B study were released showing that the study met its primary endpoint.
Detailed data from this study will be released in appropriate scientific fora. The phase III program will target a wider population audience than Synagis. So the idea is to target both healthy full-term and late preterm infants with this molecular format. This slide illustrates some of the data that supports an increased potency of 8897 in comparison to palivizumab. So RSV isolates both A and B forms were achieved, and they were analyzed in vitro. And this showed that the potency of palivizumab was, oh, sorry, of 8897 was approximately 50-fold greater than palivizumab. This slide illustrates the data I suggested that palivizumab or 8897 may achieve sufficient plasma concentrations to only have to be given once during the RSV season. These data are from healthy preterm infants.
What you can appreciate is that, for instance, at the 50-milligram dose IM, sufficiently high plasma concentrations are achieved to at least achieve a 90th percentile efficacy throughout a period that would cover the RSV season. The final program I want to discuss with you is SOBI003. This is an internal program. It targets a lysosomal storage disorder. The genetic defect is a defect in the sulfamidase enzyme. This enzyme is responsible for metabolizing certain glucose residues on proteins. What happens when this enzyme is defective is essentially that the lysosome starts storing increased levels of heparan sulfate and others of these glucose structures. The clinical phenotype of these patients is, in particular, associated with significant debilitating disease and, in particular, cognitive impairment. There is currently no treatment available, and around half of the patients may not live beyond their 20th birthday.
So SOBI003 is a recombinant human enzyme. It has been modified in some of the glycan structures with the so-called modified platform, essentially prolonging the half-life. And the idea is that this may render the molecule more susceptible to pass the blood-brain barrier. We have quite encouraging preclinical data showing also improvements in behavioral disturbances in rodents that develop the disease. We have received orphan drug designation in Europe and the U.S., and we have also received fast-track designation in the U.S. The first-in-man study is currently ongoing, and the second cohort has recently been initiated. And with that, I would like to thank you for your attention. And I think we are open for questions or.
Yes, we have time for questions.
Yes, absolutely. No, I don't think.
So I just want to ask you about the timeline for the Gamifant as well as the follow-on Synagis.
So, follow-on Synagis, when do you expect to start the phase III? And Gamifant in the secondary HLH patients and juvenile, is that phaseII study registration or study?
So around 8897, the expectation is that phase III would start in 2019. When it comes to Gamifant and the indication expansion, so the secondary HLH study, the so-called 06 study in MAS, is a pilot phase II study. And once we have now received the data, we want to meet with the FDA, and then we want to discuss what would it take to actually enable an approval, what additional data would be required.
Any additional questions?
Yeah.
Yeah, so on MEDI 8897, is there any reason that you are aware of at the moment that it would not work in preterm infants or, let's say, work less effectively? And I mean the extremely preterm infants.
The phase II-B study met its primary endpoint, and I think that's encouraging. So, no.
Yes, we have a question there?
A question about your RSV molecule and emapalumab molecules and allogeneic bone marrow transplantation, both children and adults. Given the impact of the seasonality of viruses to these guys having transplant for a wide variety of indications, but primarily hematologic malignancy,
is that a space that is amenable to these molecules? Is that something you've considered?
It is not something that we have thought much about, but I think it's a good point. I think it's a very good point.
Because once RSV hits, if you're transplanting in RSV season, it's just a gamble, actually.
Yeah, it's a very good point.
Do you delay the transplant? Do you not? And when it hits, it's devastating.
It's a very good point. Thank you.
I'm just curious on Kineret as well. In Norbert's presentation, you had the PDAC investigator data. It was not now part of the pipeline presentation. What would you need, let's say, from some of the investigator-initiated trials, for instance, to get Kineret in PDAC or other indications?
Yeah, it's a very good question. So the way we're doing it right now is we're aligning some of the, I think what I would say, most important potential indications with Kineret from an unmet medical need perspective, which also one way or the other translates into what could a business opportunity be. And then based on that, we will take a decision on which we may move forward with. At this point in time, you can say it is the pipeline of the pipeline.
Okay, thank you very much, Milan.
And then I would like to introduce Guido Oelkers again for concluding remarks. Thank you.
Yeah, thanks, Paula, and thanks, Milan. I mean, basically, I have the, let's say, honor to wrap it up. I hope you find this day useful. And the thing is, like the question you just mentioned, what it shows is probably Sobi is not short of opportunity. It is more a question now on how to synchronize it, that we meet those who basically like the profile that Henrik has shown, the cash profile, with those who like to see, obviously, us progressing into future growth areas and how to basically manage this. And that's the reason why Milan was basically making the comment that he has made. But it's clear that there is a number of opportunities that we would like to go after.
And we wanted just to make sure that you get a sense that we are really at an interesting point of time of our company development. So what we wanted to leave you behind, and nobody, clearly not me, has a crystal ball. But what we wanted to do is we feel that over the last two years, in particular, we have made substantial progress. We have worked on pipeline. We have worked on our U.S. presence. We have built out the second leg with immunology. And we have basically realized the promise to a certain degree in hemophilia, whilst we have not, we're not believing that we have maxed out. And I hope that the hemophilia discussion gave you a little bit of a sense, let's say, that it is not like a black-and-white situation. There is space for quite a number of players.
And we feel with the balance of our offering, we are actually well-positioned to take advantage of the growth in hemophilia that is taking place. There is an intrinsic growth on the patient basis of close to 5%. So from my perspective, I see really ample opportunity to build the company. And further, it brings us to the next level. We have now, I think, two super exciting products in our pipeline with BIVV001 and also with 8897, where we actually participate now in a market environment that, for the size of Sobi, is extremely material. I mean, you think about the data of BIVV001, and you basically look at where we were at the end of the seven days, and you compare this. And maybe you want to ask Dan what he thinks the trough level of some of the new therapies are.
Anyway, if you compare this with some of those notions, you get the sense that the area that you cover during this one week is extremely material, and it is clearly a product that seems to be ready for the market and that fits very well into what we call individualization and personalization of therapy, so we think that we are relevant today, particularly when you intensify the treatment and personalize it, but we will be relevant also tomorrow with BIVV001. With MEDI8897, I hope you get a sense. Yes, it's a perfect, I mean, if you just look at it purely financially, it's a perfect hedge for the lifecycle of Synagis. And yes, there will be at one stage, if the product meets expectations, there will be cannibalization.
But frankly, we will consider this as a happy problem should the product really live up to the expectations and basically confirm the expectations in a phase 3 environment. So for us, when you think it through, I mean, we still believe opportunity for growth in hemophilia. With Synagis, I think you got a taste when you had this funnel from 63k to 18k who get full treatment. We think there is something to gain. And for us, as a company, Synagis is our second largest product. This is not priority whatever, 75. This is, for us, second largest product.
You can expect us, with the team that we have got that is very enthusiastic about doing the right thing for patients, to work on basically the attrition, but to create the right level of awareness and the right degree of focus to build this up. Are we promising that this is an exponential growth product? No. But we clearly are convinced that we have a substantial opportunity when you just look at the mechanics of doing the right thing. We will not be shy to provide the evidence that has been gathered by AstraZeneca to basically give regulators a choice, maybe to rethink whether actually the guideline change a couple of years ago was in the best interest of patients. That's for others to judge. We will just make this data available. That's on this side.
And then you basically come to Gamifant, where basically you have seen obviously the majority of the patient population is in secondary HLH. And basically just you have two angles that basically will drive over time the product growth very materially for the company. It is obviously moving into these indications from primary into secondary for children and into secondary for adults. And then obviously we want to get into those with graft failure. So expand from there. So you have an indication development over time that will be documented with the studies. And then there's the geographic angle. And what maybe might have looked like a small addition, but the countries, like the second wave countries that we brought on the way with Switzerland, Canada, with Japan, let's say this represents 60% of the patient potential of the United States. Because there is a high prevalence in Japan.
So it's very material what we brought on the way. And then obviously we are working on the U.S. in November. So there's the geographic dimension. And basically to the question that was earlier asked, how do we think about now, let's say, basically the permutation of the product into other indications? I mean, we have limitations, to be honest, to what we provide, to what we can promote. So for us, it's very difficult, to be honest, to give you here a solid answer. What we will do is we have obviously compassionate use programs. We will try to beef up our clinical trials in adults. And then there will be obviously clinical decisions with physicians where we will have to deal with this in a very responsible way, how the product is made available. And that's basically then more like a case-to-case decision.
But what you see is that with emapalumab, we are hitting a space with a huge unmet medical need. And we are currently also rethinking how we deal with this because there is a high demand. And we can see this. And you have seen some of the sales data. So basically, when you look at it strategically, we don't actually, it's quite actually gratifying when you think about strategy being a deliberate and an emergent element. So far, we have no reason to change our course of direction. We feel absolutely encouraged to continue further working on United States, further working on the immunology part, further diversifying there, thinking of reaping the benefits in BIVV001. We're obviously committed to hemophilia. And we want to be recognized as a player today, tomorrow, and tomorrow after.
Basically, when you think about the guidance, I mean, as you know us, let's say we are probably not those guys who want to delight by big, let's say, promises, but more by what we deliver. We don't want to change this. So hence, we are sticking to our guidance for now. But we see we are very encouraged by the first quarter. And obviously building now a couple of these concepts. So when you think through, also for your assessment on the hemophilia side, the question is, how is this going to play out? This will be, in the end, your judgment. We have provided you with some ideas, how we think about it, and brought this into perspective. But we think that the opportunity for us to expand in that field is larger than maybe the pressure that we get from new therapies.
And that's the reason why we are still optimistic. So I think this gives you a little bit of a wrapper. So you see us absolutely bullish, let's say, as we go into the future. And obviously, we will look further for M&A, given the fact that we have that capacity that we can unload on the company. So we are looking for something that basically further allows us to make the next step change and bring the company forward. On this note, I think we'd like to thank you for your interest. And maybe we open the floor for questions. And my colleagues and I will be obviously ready to answer any. Yeah. Thank you.
Thank you very much. A couple of questions. The first one to your hemophilia strategy of driving penetration. You've previously stated that Europe is different from the U.S.
One good example we just heard about today is that of costs, which is definitely something that differentiates Europe from the U.S. So is your strategy in hemophilia to expand into markets where, let's say, the competition will have more difficulty in entering due to cost and where you can play on the tender cards, which also suggests that you would invest more in expanding into other countries or new countries within your territory? So that's the first question. And then the second relating to your M&A and strategy, how do you view that? I mean, with synergies, you changed the narrative to now having an immunology platform. And when we typically think about a platform, it's something that is scalable. You add more drugs onto a scalable platform.
And when you bought Synagis, as far as I can recall, you talked about the potential for, let's say, trimming on the personnel side. Now we are learning that you are actually adding to the personnel side to sort of drive sales. How do you view, let's say, new acquisitions? Are they to, let's say, leverage what you have? Or could you consider all of a sudden we have a fourth leg to Sobi? Just some high-level thoughts on that one. Thank you.
Yeah. Thanks. So maybe I start with the hemophilia side. I mean, the European markets are obviously invariably more complex and not as homogeneous as the U.S. environment. So what you basically we adapt to those environments as they come. So we are competing in tender markets.
And we are quite gratified that in various tender markets, there is not only a recognition of price, but there is also a recognition of what the product can do actually for the patient. And sometimes, not always, we get at least some recognition of the improvement that we bring to patients. And then we adapt our pricing accordingly. So we are basically our main objective is to do the right thing for patients. And we will expand. I mean, in a geographic angle, we have not really made any great strides in the Central Eastern European piece part. And there we are currently in a launch phase, really on a very modest level. But we just started this year really to get our foot on the ground.
And we have very significant growth opportunities in wide parts of Europe still, like even in Germany and many in big parts there. We are not at the level that we can be satisfied. And also in the Benelux area, we are not satisfied. In Spain even, so we have seen some good growth. So there is a lot of opportunity still for us to take what we would consider fair share. And we will step up the activity. And for us, obviously, the hemophilia piece, when you think about it, this is not a priority. This is the priority. So you can imagine that the temperature level and the focus is pretty high. And when you get a sense of this liberating life, this is not just a marketing campaign that we all want to do to make people feel good.
This will be now supported by clinical evidence and with a very comprehensive program. We will unveil quite a few new elements during the course of this year. Because we are thinking that we really want to provide patients with a choice that you have at least a choice not to forget about your disease, but to actively manage it. This is what we will stand for. This is basically our approach there. We will. With these prices, there will be price pressure, obviously. It's clear to what degree. So far, we have been able to manage this and offset this quite well, obviously with the unit growth, but there will be this. We think that the opportunity for us, also with the geographic expansion and with the penetration, is still quite substantial. We believe that this is a good offering.
Now, basically, with regard to your second part of the question, M&A, I mean, obviously, we added now the Synagis organization, so the leverage that you will get is, and this is what we're currently looking at, is to what degree could Synagis in a second phase of the launch of Gamifant help us to create awareness at a pediatrician level? Because this is where we are extremely well penetrated, because one of the key issues, obviously, is that HLH as a syndrome is not very well understood, and we have many patient cases where the patient actually doesn't know for two years or the family that the patient has actually HLH, so you get misdiagnosed a lot, and then the question is, could we use this team in this funnel, essentially, to make sure that patients get quicker diagnosed? This is currently what we are doing.
This is one of the chief tasks that we are currently undertaking with the new leadership in North America. So there will be some synergy, but it is not yet. But fundamentally, when you think about what we got, the 135 FTEs, that these 135 is a beautiful platform for building out a pediatric element. So while it's a linkage to our existing business, we still have to articulate in a much more clearer way. And we will do this once we have concluded. I think it is a beautiful opportunity for us to build portfolio on this pediatric angle. And there, you can expect us to think further. And when you think about portfolio, I think we have now two legs, immunology and hemophilia, that gives us a significant opportunity to build out. Because as Norbert has pointed out, I mean, immunology alone is enormously broad.
And there, you can expect us to explain further to you in the coming months how we see our focus on immunology evolving. Do we need another leg? I think for me personally, at this juncture, it's probably early. We will, at one stage, always reassess what opportunities the foothold in Specialty Care give us. Because Specialty Care, we left it, and I mentioned it at some meetings. We purposely called it Specialty Care more as a working title. Now we broke out immunology. It potentially could give us an opportunity to do something else at one stage. But we are extremely excited about what we can do in immunology and in hemophilia that maybe at one stage we also take broader into a realm maybe of hematology. So this is something we are currently thinking about. So as far as possible, we want to stick to anything.
Eric, you have it.
Thank you. Just to follow up on the M&A agenda that you have, could you elaborate a little bit on your priorities in terms of pipeline and long-term growth versus short-term opportunities? And also on that question, if you look historically, it seems like your deals have been more adding sort of on-market products or very limited development risk pipeline projects. Would you consider taking more biological risk in future deals, i.e., going adding some phase I, phase II assets?
Yeah. I think absolutely. I mean, when you see the company evolution, 2016, SEK 5 billion, 2019 forecast, depending on which range you take, let's say, give and take a SEK 13 billion. So a bit of an evolution, obviously, earnings followed suit. Let's say so that basically enables us to think broader. I think for now, we still will look from the right, meaning to the left.
Humbly, I would like a little bit to disagree with you that actually when you look at the Synagis deal with 8897, and let's say, and also the emapalumab now with the development project in late stage, actually we have done, considering the scale of the company, actually quite a lot. Yeah. And maybe it's always in the eyes of the beholder. And don't feel for a second that we are satisfied with this. So we will do more. But I think at this juncture, we still start from the right, working our way to the left. But we will soon start looking also at phase II assets and assume a larger risk. But at this juncture, when we talk particularly to our investor base, we get the sense that investors like to manage the risk profile of the company and make sure they like to see growth.
So we want to make sure that the company continues having a very strong growth trajectory. And that's what we're currently cementing. But as we go along and become larger, we will also be willing to assume more risk.
As final, secondary to that, in hemophilia, I note that many of your competitors have either partnered or invested directly in gene therapy. Is that totally out of the question for you? Or would you consider some type of deal there for the long term?
I think it's not out of the question. It's more a question of opportunity. And the thing what we are currently thinking through, and there we are connecting very close with academia, is the risk-reward ratio. And let's say, are these formats that are closer to market the formats of tomorrow? Or are they?
And because there are quite a number of question marks, and does this risk profile fit to basically our profile as a group right now? And personally, I think we still have more grounds to cover with Gamifant, which has a very different risk profile and a very substantial upside profile. But we will continuously look at this, obviously, because this is an emerging area. There's a big promise. Intuitively, when we debated it, let's say, we say, is hemophilia now the area where gene therapy is the most intuitive one to make a big splash? Not sure. I mean, the unmet medical need is maybe less pronounced than in other areas. But it is definitely something we will look into those areas and we'll see when is the right angle, when do we hit the right risk-reward profile so that it fits to our company.
I have two questions. So earlier, you showed a slide on the products contributing to near-term and medium-term growth. So what's the time horizon for midterm for you? Next to three to five?
Three to five.
Okay. And then in terms of another question on M&A, so you talked about three different areas. One is late stage on-market products and then geographic expansion that you have been doing. But the third one was a transformational M&A. So question, there are two questions. One, is your next move in M&A be transformational deal? And what kind of transformational deal? How does it look like from your perspective? What constitutes a transformational for you?
A transformational deal, in my books, would be a deal that basically really stretches our capability in terms of financial capacity that basically is a very significant scale in terms of acquisition beyond what we have committed in the Synagis deal. And there we would basically look at different angles to the deal. What basically is how do we create? Do we change the scale of the company? Do we change the profile of our pipeline? Do we do anything on platform? Though that basically is something that we will look at as a three-dimensional perspective. The dilemma of these things is they're only real once you have done them. So in the meantime, we will continue trying to do well on our pipe, let's say, and find one or the other asset that we fit into our core portfolio late stage.
And there we have one or the other deal. But we will look at doing during the course of the year into other areas. But the dilemma is when you look at those deals, they are not so many in rare diseases. Then secondly, they are well looked at, well thought of. And then they are also at a reasonable price tag. So we will have to have a little bit of our thinking caps on, let's say, on how we make sure that we are not perceived to overpay. I think this is always a huge concern. And B, that it does enough to the company so that we can see also some synergies, let's say, substantial synergies that drive us, whether it's on the cost side or in the so I'm afraid it's a bit vague.
But I'm also afraid because I'm aware these deals are only real once you sign them. And let's say until then, you can have a lot of philosophy, but we think a little bit larger. Because again, our objective is to build a leader in rare disease and fill the space that basically is there for us after some leaders were consolidated away. So we want to grow into the next scale, and that will need a significant effort. And so far, we feel that we had the right hunches when we did deals, and we don't want to change this habit.
So now you're expanding in the U.S., kind of like getting the Elocta and Alprolix rights back from Sanofi. Would that be kind of your consideration for the future?
I think at this juncture, let's say we are happy to have Sanofi as a partner.
And they obviously have a formidable resource base. And we have an open dialogue with them. And let's say, but I don't see signaling from their side that they would be interested to give up this position given that they have just set up this rare blood disorder business unit under Sanofi Genzyme. So I think I'm not sure that this is. I don't want to speculate, really. But it's an interesting thought. Previously, people thought the other way, let's say, and let's say around. But for us, we have the realities. We are quite happy in this partnership. So I don't want to spur any rumors.
Thank you.
Thank you.
Just one follow-up question. Thank you. Would you be comfortable in giving, let's say, long-term financial targets in order to mitigate the negative impact that the Hemlibra overhang has on the share? Thank you.
Yeah.
I mean, we debated this, yeah, because as you can see, you don't see us here extremely depressed or sorry after over 90% earnings growth in Q1, but share price didn't react, let's say, as maybe the one or the other was hoping for. I don't think that basically I mean, we debated it, and basically our conclusion is we don't want to make promises we will deliver. Judge us by what we do. Don't judge us for what we tell you, and let's say, and we hope that we can show you good growth in Q2 and during the course of this year, and then basically, let's say the audience, I hope we'll conclude anyway, what is a right level for us. And I think this is a better promise than getting ahead of ourselves and making big promises here. We just deliver.
And let's say this is our focus now as a team. And trust us, we are really laser-focused on the subject and hope to delight. Yeah.
Thank you very much, Guido. Thank you. Thank you all for joining us today.
Thank you.