Good morning, ladies and gents. We'll make a start. Welcome to CSL's Annual Research and Development Briefing. Our first speaker and host today is Doctor. Bill Mazzanoti, Executive Vice President and Head of Research and Development.
Before we start, be aware this presentation is being webcast, and please use the microphones during the question and answer session. Please note the forward disclaimer statement contained in your packs. And with that short introduction, I'll pass you over to Bill. Bill?
Good morning. Thanks, Mark, and welcome. I'm Bill Mezzanati. I took over as Head of R and D last year, and I'm running the R and D Day today. Before we start, I'd just like to acknowledge Andrew Cuthbertson, who's in the audience.
Andrew, for his leadership and support over the past few years when I've been here and also, of course, many years in running this day. And Andrew will be around all morning. And if you can pin him down, he's happy to answer questions for you. As Andrew likes to say and Mark likes to say, we do take your feedback seriously. And we try to organize the day based on what you've asked for since really the days for you, not for us.
So we will continue to strive to do that. We have a lot of good things happening in R and D and some of which we could talk about and some we can't just because we didn't have enough time. So please give Mark some feedback as we go along. A couple of things. First, the theme of this year for me is really progress.
R and D has made a lot of progress this year and a lot of good things are happening in R and D. AAGES 2, our trial cardiovascular outcome trial for CSL-one hundred and twelve is progressing well, recruiting well. We'll talk about it later. But it's continuing to make great progress. We have new IG programs and we continue to build on our IG franchise that we have to date.
We have a lot of new Phase 1 starts, which we'll get into, which of course is for the health of the future portfolio and pipeline. And we've fully implemented our TA model, which we'll come back to as well. Of course, R and D is a multi year process. And unfortunately, despite our best efforts, we can't really align all of our milestones with this R and D Day, but we will do the best we can. And of course, we are in control of many aspects of our programs, including the execution that some things like health authority interactions, when they happen, how they go are slightly out of our control as our recruitment of clinical trials somewhat out of our control too.
So the timelines we put forward are best estimates, but generally never perfect. We do pride ourselves in making wise investments. We take the investment of your money seriously and try to make sound judicious decisions with those investments and taking into account commercial liability, clinical need, etcetera. And we have both a rigorous stage gate process that continues to reevaluate our investments and a portfolio prioritization that takes a look at things and decides where are the best use of our dollars, our people, our time and our attention. And so what you see today reflects all of that happening at the same time.
So today joining me are Andrew Nash, our Head of Research and Diana Lancione, our Head of Clinical Pharmacology and Translational Medicine or Early Development, some people like to say. And Diana is in charge of Phase 1 and 2 development for our program. And it's very important that we have a tight link between research and early development as you move a portfolio for along. And I would like to be to complement the 2 of them and say we have a really great interaction and collaboration between the groups, which helps us to maximize our portfolio. We had very good feedback from you last year about our presentation on the flu business, which we hadn't done for a while.
And so, Russell Vassar, the Head of Securus R&D is here to give you another update today. And back always by popular demand is Bill Campbell, our Chief Commercial Officer. And we'll have 2 Q and A sessions and we'll invite all the panelists up for both parts of that. So this is a map of our global R and D footprint for Securus and for Barron. It changes a little bit, but not a lot in the last year.
Good news is we found last week that we had forgotten the circle for Sydney. And I was glad before I came up here that I put that circle up here. And it reflects a few things. 1, we put our R and D hubs in the parts of the geography that are important to our business. And second, of course, we have a strong hub in research for Behring here in Australia, in Melbourne, embedded into the Melbourne Medical Campus, which gives us, we believe, a great advantage in innovation and collaboration with really leading clinicians and scientists.
But that's only part of the hub. We also have clinical and regulatory hubs in North America and in Europe. And that's important, of course, because that's where the density of patients and some of the important health authorities sit and so that makes sense as well. But together we're interconnected, making sure that we leverage all the strengths and interest across the world and avoid duplication and unnecessary costs whenever we can. The same is true for Securus.
And for both of us, of course, we have an interaction with world concentrated again in our three regions of North America, Europe and Australia, where we leverage their expertise, which magnifies our own expertise and helps us to create as vibrant a portfolio as possible. You've seen the slide before, which is our commitment to R and D and envelope that we have said to you before. Not surprisingly, the spend is concentrated the spend is concentrated mostly in new product development and life cycle management, because of course, that's where you need to spend money on new clinical programs, new research programs in order to bring them to market. Market development, which we'll come back to in a couple of slides, of course, is primarily a regulatory safety and somewhat clinical affair taking advantage of data generally we've already generated around the world. So we have continued to spend.
We will likely spend a little more this year, but we'll stay within that 10% to 11% envelope. And the real reason for this spend, of course, is to create a portfolio going forward that assures growth for CSL in the decade to come.
I would say,
lastly, not only are we spending on projects, but of course, we're spending on highly qualified individuals that can run these programs. So experienced biopharmaceutical executives and scientists from around the world have been joining CSL, which is we really need because we have such an exciting and diverse portfolio that we're bringing forward. Of course, one of the places that R and D continues to commit to support and actively supports is our plasma business. We have over 250 scientists in plasma product development, whose job it is to enhance the growth of our plasma business. And they do that in 4 main ways.
1, in close cooperation with operations, The technical operations is designed to enhance processes and ensure our continued plasma supply that we have currently. 2nd, we have continual process improvement there to improve our processes always, constantly looking for ways to increase efficiency or yield, both of which are very important to the business. 3rd, we have patient focused devices and formulation, which help to enhance our products. And lastly, new products and new indications of which we'll talk to a few today, including Hemopexan and haptoglobin. Taken together, these create a lot of strategic support for an important part of our business.
This is our therapeutic area framework, which we've talked about before and now is fully built out across the 6 therapeutic areas, immunology and neurology, hematology and thrombosis, respiratory, cardiovascular and metabolism, transplant and of course, influenza vaccines. And built upon the platform strategically that help support the new opportunities we find. And cell and gene therapy, of course, is our newest platform, but has some similarities we believe in the way we approach it that will help us be successful there like we have with vaccines, plasma and recombinants. Taken together, this makes for an exciting unique portfolio and moves us closer to a fully integrated plasma based biotechnology organization. Importantly, these TAs are run by both R and D and commercial, so that our new opportunities are scientifically sound, clinically applicable and commercially viable.
Going forward, we'll report portfolio progress using this framework. Individual projects will still be reported individually. But importantly, commercial, the progress we make, we will still use the nomenclature such a specialty that you're used to in the past. This is a reference of the 2018 portfolio and where we start from for this year. This is a slide we love to show and we hope to continue to love to show, which is our key launches from the R and D portfolio.
This is over the last 7 years, which represents a lot of new exciting medicines that have added a lot of value to patients and of course to CSL. And in 2019, we continued with launches of CIDP for Hizentra and Privagen in Japan, a very important market for us. And very exciting, just recently, we heard from the FDA that we have been granted orphan exclusivity for CIDP for Hizentra in the U. S. And of course, Fusilvax Quadrivalent and Afluria Quadrivalent for younger age groups in Europe and Australia were also launched this year.
So again, some great progress. Other progress that doesn't often show up on our portfolio slides, but is important, is the work we do around the world in market development to bring our medicines to other parts of the world that need the medicine and of course, add value. And here's just a reflection of some of the work that's gone on by our regulatory group in diverse parts of the world, bringing products from both bearing and Securus to these markets. And this helps add, while it's not that visible, it's very important. It helps add to the balanced commercial productivity that Bill Campbell will speak about when he's up here.
So this is a slide on clinical progression in 2019. It's a bit of a misnomer because progression for us means something that's moved from one phase of development to another. So there's lots of progress going on that's not progression in our technical parlance. So things like CSL-one hundred and twelve is progressing well. Their transplant programs are progressing well.
Early research, we have a number of programs that have made really nice progress in Andrew Nash's organization. However, they don't show up on this slide because they haven't passed some technical stage gate or phase. But what you do see here are a few things. 1, you see on the left, a number of programs entering Phase 1, which is what we expected to happen and how we've been building the organization in anticipation. Two programs I want to highlight.
CSL-two hundred is our first gene and cell therapy and it's screening patients now for sickle cell disease, a devastating disease, genetic based disease of patients of primarily African descent. We have a second program aimed at patients with sickle cell, a slightly different approach, but using a plasma based approach, Hemaphexan and Diana will speak about them later. She'll also speak about new starts for immunoglobulin, Privagen and Hizentra in systemic sclerosis and Hizentra in dermatomyositis, both recruiting patients now. You also see again a number of pieces for Japan on the right. And that's important because Japan is a very sophisticated market that values innovation and often supports it through their policies.
And that's very important for us and for patients. And lastly, of course, through Afluria, Flucelvax, Fluad and the pre pandemic, we're doing very nicely in the, Securus arena as well. Haptoglobin was a project last year, we mentioned and said it was not. It had been sent back to research. Well, Andrew will talk about it today and talk about how we've moved that program forward in a new indication.
So we continue to recycle when we can. Sorry, the last thing I want to mention, so we had a great year in R and D, but not everything went perfectly. We have a few programs that we highlighted last year I need to mention. CSL-seven eighty 7, our nebulized IG for respiratory indications, meant to go into Phase 1, but because of some extra preclinical work, extra formulation work to make sure the respiratory formulation was right and some work optimizing our nebulizer that has not gone into Phase 1 this year, but we hope so next year. Unfortunately, that is the nature of inhalational development.
I have seen this before and experienced it before. CSL 964 for GVHD, we'll talk about it. It was meant to go directly into Phase III. However, after more clinical and regulatory evaluation, we decided to create an adaptive Phase IIIII design. And that will take a little longer, maybe up to 6 months longer, but we think gives it higher chance of success.
CSL-eight nineteen, C1 inhibitor for DGF was meant to enter the clinic this year. But through our portfolio prioritization process, we decided that our efforts were better used on the other transplant programs. And that the C1 inhibitor will be best used in both the AMR trial and the and for HAGAR to patients. And of course, we all have other products projects in our portfolio, which may be better for ischemia reperfusion injury. So we're going to take a pause and take a look at that just as we
did with
haptoglobin. And lastly, the Factor VIII from China that we mentioned before. We told you last year that reviewing the dossier, we thought there were some elements of it that weren't quite up to our standards. So we took a pause. We're continuing to do manufacturing and plasma product development work there.
And so we'll park it right now in Phase 2 of our pipeline, and we'll give you some updates when we've had some product development progress there as well. We do have partner programs that are important to our portfolio. I won't go in them within them today, but some of them we do ourselves for our partner. Some of them we out license when the partner can do a better job than us or when our strategic focus is not there. And some like those in Phase III, we let the partner run primarily, but we can take advantage of these data later on if valuable.
And so here's our new snapshot of our portfolio, balanced across therapeutic areas, representing all 6 therapeutic areas, representing our partners. The last thing I'll say about it, in a number of places, you'll see a number of approaches to the same disease. This is intentional for a couple of reasons. 1, it helps increase our probability of success. 2, the approaches are not absolutely overlapping, they're partly overlapping either in indication or approach or mechanism.
And therefore, if they're both successful, we can and may be able to figure out ways to use them together. But last, it also helps concentrate our knowledge and expertise and development work. So we're taking full advantage of all the work we're doing. So with that, thanks for your attention. I'll turn it now over to Andrew.
Andrew?
Thanks, Bill, and good morning to everyone. It's my pleasure today to talk to you about some of the things that have been going on in CSL Research over the last 12 months. Probably the most important role of research is to deliver new development opportunities to the organization. And to do that, we need to be able to recruit the best scientists. We need to be able to place them in really high quality laboratories, in precincts and environments, which really facilitate innovation.
So I will spend some time to start with talking to you about our capabilities and some of the new facilities that help out with that. I'm then going to talk about 3 projects in particular. And these projects have been selected not only because each of them meets an important unmet medical need, but also because they exemplify the way we deploy our technology platforms. So I'm going to talk about the use of haptoglobin purified from plasma to treat subarachnoid hemorrhage. I'm going to talk about a recombinant antibody that we're developing for inflammatory disease.
And I'm going to talk about a gene therapy product that we're developing for sickle cell disease, but also the next step of that process, which will be a move into immuno deficiencies. So in terms of facilities, I think when I spoke last year, we had almost completed the construction of our new facility at the Bio 21 Institute in Melbourne. That has now been completed and is occupied by our staff there. We have about 130, 140 scientists based there. I think most of you will be aware that the Parkville precinct is one of the world's premier medical research precincts.
And that certainly us access to great scientists, great clinicians and certainly the ability to do 1st class translational science. In a sense, we've reproduced that setting in Bern, where we've moved our research group from our manufacturing facility into the Swiss Institute For Translational and Entrepreneurial Medicine. This is a new facility located on the Bern University Hospital site. And again, it gives us great access to innovation and Gene therapy, as you know, we acquired Calimmune a number of years ago, Gene therapy, as you know, we acquired Calimmune a number of years ago now and we've made a really strong effort over the last couple of years to expand our both our expertise, our research expertise and also our capability in the areas of GMP, cell manufacturing. And so we have a new facility that we've built out in Pasadena that will enable us to push forward with our CSL-two hundred study, but also other studies into the future.
And one thing that's not shown there is the construction of our new R and D building in Marburg. So that just started probably a month or so ago now, and it's a really important development for the Marburg site. I think it will be critical in both our ability to attract scientists to that site and the quality of the work that will come out there. So a considerable investment in research and development facilities that I think will elevate the quality of what we're doing. Look, another point I just want to focus on for a minute is the way we access external innovation.
I think most of you who have been coming to this day for many years will realize that our internal innovation has been a really strong driver for new products coming onto the market. But to be competitive, we really have to be good at accessing external innovation and external ideas. And we've taken a very strategic approach to this. We have a really high quality group based within research whose focus is on external innovation, accessing that innovation to bring it into our pipeline. So we leverage our global research sites to access strategic partnerships with universities and MRIs.
We look at funding and collaboration initiatives. Here in Australia, we have a really good partnership with a venture capital group, brand and capital partners through the Biomedical Translation Fund. We have partnerships with biotech companies. I think Bill mentioned Mementia and Aslan. And of course, we attend all of the partnering conferences looking for new opportunities.
So a nice strategic approach where we target what we think are the highest quality institutes and universities to work with them to access innovation for our pipeline. So moving on to projects. The first project I want to talk about is the use of haptoglobin to treat Subarachnoid hemorrhage is a devastating acute neurological disease that results from the rupture of an aneurysm, which leads to bleeding into the subarachnoid space. One of the issues here is that if you survive the initial bleed, you're at a high risk of subsequently developing what are called delayed ischemic neurological deficits or DIND. The cause of this remains somewhat obscure, but there's really strong evidence now to suggest that it's the result of the lysis of the red cells that have gone into the subarachnoid space, the release of hemoglobin and the toxicity of that hemoglobin.
And I will talk a little bit more about that. It affects about 30,000 patients every year in the U. S. And it's associated with high mortality and morbidity. And there are really very limited treatments available at the moment.
So it's really an area of unmet need where we think we can do something about it using a plasma based protein haptoglobin. I mentioned the role of hemoglobin. Hemoglobin is thought to affect the development of the disease in a number of ways. Once it's released into the subarachnoid space, it can delocalize into the brain parenchyma, where it leads to the depletion of nitric oxide and vasoconstriction. And it also leads to the generation of free radicals, which cause tissue damage.
So there's strong evidence for a role for hemoglobin and that's really highlighted on the following slide, which gives you an example from one patient and from a cohort of patients. So on your left there, you can see that CSF, cerebrospinal fluid has been sampled from a patient that presented at the color to red and back again. And that redness is associated with the lysis of red cells in the CSF and the release of hemoglobin. You can see there that the accumulation of hemoglobin has been followed and that correlates with the start of delayed ischemic neurological deficit. And you can see at the highest point there, there's a treatment with a calcium channel blocker to relieve the vasoconstriction.
You have a cohort of 18 patients that have been divided into the groups that you have a cohort of 18 patients that have been divided into the groups that developed neurological deficit and those that didn't. And you can see that the ones that developed the neurological deficit clearly had much higher exposure to hemoglobin. So a lot of circumstantial evidence that one of the main drivers of ischemic neurological deficit following subarachnoid hemorrhage is hemoglobin. So this begs the question, what does the body normally do with free hemoglobin when it's released? And can we harness that mechanism to treat this particular disease?
So I think you've seen a slide similar to this previously when I've talked about this area. So when red cells lies, they release hemoglobin. That hemoglobin subsequently breaks down to heme and the heme subsequently releases iron. And each of those agents, hemoglobin, heme and iron can have a toxic effect. The body's mechanism for dealing with that is shown in the bottom line there, where transferrin can interact with iron, hemopexan reacts with very high affinity with heme and haptoglobin interacts with hemoglobin.
So we feel that there's an opportunity to use haptoglobin and hemoPEXAN in fact to treat chronic and acute hemolytic diseases. So we can use hapoglobin to remove hemoglobin from the circulation and where necessary, we can use hemopexin to remove heme. In many of these conditions, whether they're acute or chronic, it's very clear from analysis that's been done that both haptoglobin and hemopexan are very significantly depleted. So the stores of those molecules are used up, which makes this a replacement or an augmentation therapy. So that's what we're attempting to do here is to restore the body's levels of haptoglobin and hemopexan.
And as I'm talking about haptoglobin for the treatment of subarachnoid hemorrhage, We are also, of course, developing hematopexin for a chronic hemolytic disease, which is sickle cell disease. And Diana is going to talk a little bit about that in the next slide or in the next presentation. So we've been working in this area, funded with by the Swiss government using an inner Swiss grant and partnered with the University Hospital of Zurich. And all of this data has just been published in a fantastic publication that was published in the Journal of Clinical Investigation in the middle of November. So the data is all available in much more detailed form that I'm going to show here, but I'll just pick out some of the highlights for you.
So using CSL heptoglobin purified from plasma, we worked with our colleagues at the University Hospital Zurich, to develop a shape model to study subarachnoid hemorrhage. And on the left there, you can see we have both an in vivo model where we administer hemoglobin into the sheep brain and look at the effect that that hemoglobin has. And also, we have an ex vivo model where we take a sheep brain artery and we're able to measure constriction and dilation of that artery ex vivo. And we've generated some beautiful data from that, which supports the role of haptoglobin in the treatment of this disease. So on the right there, you can see some data from the ex vivo model where we're measuring constriction or contraction of the vessel and relaxation of that artery.
And you can see that if you expose that vessel to hemoglobin, you lose the ability of the artery to dilate. And that's shown by the red line that runs across the top. If you expose the control vessel to a nitric oxide donor, then you get a nice relaxation of the vessel, sorry, and that is prevented by the hemoglobin. If ahead of adding the hemoglobin, you combine it with haptoglobin, you completely prevent the effect of the hemoglobin in terms of its ability to stop the relaxation of the vessel. So CSF from sheep that's been treated with hemoglobin causes constriction of the vessel and haptoglobin protects against that.
You can see that, that translates directly into the human setting as well, where we've taken CSF from patients that have had subarachnoid hemorrhage. And that CSF in this ex vivo model prevents the relaxation of those vessels when they're exposed to a nitric oxide donor. So some really nice ex vivo data that a, hemoglobin causes vasoconstriction and, b, that in the presence of haptoglobin, that vasoconstriction is ameliorated. That same effect was we could map vessels that were constricting in response to hemoglobin. And we were able to show very clearly that when we mixed the hemoglobin with the haptoglobin, the vasoconstriction was reversed.
So what is the mechanism that allows this to occur? And really, what is happening is that the combination of haptoglobin with hemoglobin prevents the hemoglobin from delocalizing into the brain parenchyma into the brain tissue. So here we've infused a fluorescently labeled hemoglobin and you can see on the bottom left there, the hemoglobin diffusing into the brain parenchyma. If the hemoglobin is already mixed with haptoglobin, you can see in the middle there that it does not diffuse into the brain parenchyma. So it's a size exclusion effect, the large complex of hemoglobin and haptoglobin cannot diffuse into the brain parenchyma.
And you can see some close-up analysis there of the right. So the mechanism here is that red cell lies, red cells lies, the hemoglobin is released and instead of normally as it would delocalizing into the brain parenchyma in combination with haptoglobin, unable to do that. So to summarize this program, for hemoglobin, we know that the concentration of hemoglobin in CSF correlates with neurological deficit. We know that it rapidly penetrates from the CSF into the brain parenchyma. And we know care of analysis, both in our model but also in patients, that penetration of hemoglobin into the parenchyma induces vaso spasms.
And in our model, it induced vasospasm in 100% of the animals. We know that haptoglobin blocks tissue penetration of cell free hemoglobin and I showed that on the low slide. It prevents hemoglobin induced vasospasms ex vivo and it prevents hemoglobin induced segmental vasospasm in vivo. So some really very exciting data for the use of plasma derived haptoglobin as a treatment for neurological deficit resulting from subarachnoid hemorrhage. And we're making some nice progress with this project and we're hoping that it will enter development in the second half of next year.
Moving on, the next project I want to talk about is not a plasma protein, but a recombinant therapeutic antibody. And we've developed a number of these at CSL over the years that have moved through into clinical studies. And this one, CSL-three eleven, has been developed for the treatment of inflammatory disease and in particular, airways inflammation, for example, asthma or nasal polyposis. The really interesting and unique thing about CSL-three eleven is that it targets multiple cytokines. So I'm sure many of you will be aware that the inflammatory response, whether it's in airways or in joints or in other tissues, is mediated by a series of growth factors or cytokines.
And there are many therapeutics out there which particular target particular cytokines in order to treat that inflammation. We know in airway inflammation that myeloid cells play a particular role. And if we think about the production and activation of myeloid cells, we know that GM CSF, IL-three and IL-five play a role in the production of those cell types from the marrow. And then beyond the marrow, they play a role in the activation and the lifespan of those cells in the tissues. And in particular, in this pathological setting, we know that they contribute to the accumulation of these myeloid cell populations and their activation within lung tissue in the context of asthma.
And you can see on the right there what happens when this occurs, you get inflammation of the vessel, you get mucus secretion, you get hyper responsiveness of smooth muscle as well. So 3 cytokines that we know are important to the development of inflammatory disease and airway inflammation in particular. Now the unique thing about these 3 cytokines is that they share a common receptor. So while each of them has an individual alpha chain receptor, they all make use of the same beta common receptor. And that gives us an opportunity to target all 3 of them with a single agent.
So what we've done over the last number of years within research is develop an antibody called CSL-three eleven, which targets that beta common receptor to block the activity of all three cytokines very potently. And you can see that that data has been published not too long ago in the journal shown on the right hand side there. We've shown through a whole series of in vitro experiments that 311 is a potent inhibitor of each of those cytokines and more importantly, a potent inhibitor of the effect of those cytokines on a whole range of inflammatory cells that contribute to asthma. We've also developed a really nice in vivo model to follow this. In vivo models, mouse models, non human primate models of asthma are not great and they don't translate very well.
But one model of airways inflammation that we know does translate well is a model of nasal polyposis. And this the biology of this is very closely related to asthma. So we know a lot of patients with asthma have nasal polyposis and the reverse is true as well. So the mechanisms underlying both diseases are very similar. So a drug that impacts nasal polyposis
will have
a very high chance of impacting in asthma. So this is the model that we've developed to be able to test 311 in nasal polyposis. We sample nasal polyps from patients. You can see one there. And we transplant those nasal polyps into immune deficient mice and then we treat those mice with CSL-three eleven.
And again, this data has just been published recently in allergy, and you can look at the data in more detail if you like. But just to give you a sample of the data that we see, we can follow the growth of the polyps, we can follow the cellular composition of the polyps and we can follow, for example, mucus production within the polyps. And you can see on the left hand side there that 311 is a potent inhibitor of the growth of the polyps. But really interesting, if you look on the right hand side there, you can see that it has a potent effect on the production of mucus by mucus producing cells. So that's a really interesting observation.
And when we look at this in really great detail looking at the RNA transcriptome, we can see that 311 has an effect not on a number of other pathways that are connected with disease. So beyond influencing the activity of IL-three and IL-five and GM CSF, we can see down regulation of the IL-thirteen and IL-four pathway as well, which is associated with the efficacy that's been seen with Dupixent. So both our in vitro data and this really important in vivo data give us a really, I guess, strong hope that 3 11 will be effective in the treatment of this airways inflammation. So in summary, CSL-three eleven is a potent antagonist of the 3 cytokines that we've been talking about in vitro. It inhibits the activity of multiple cell types involved in inflammation.
We've developed a really nice in vivo model of disease and 311 has a potent effect in that model. And we've completed toxicology and have moved into clinical studies. And Diana is going to pick up on that in her presentation coming up to just give you some more information on that. The final thing I want to talk to you about today is our efforts in gene therapy. And just a little bit of background at the start in terms of in vivo versus ex vivo gene therapy and to distinguish what we're doing at CSL compared to what a number of others are doing.
So really, at this stage, there's 2 types of gene therapy that are being pursued, direct delivery and cell based delivery. So direct delivery primarily uses adeno associated viruses. The missing gene is incorporated into the adeno associated virus and that virus is delivered with the hope that it will localize into the tissue of interest and express the missing protein. There are a number of problems associated with this. One of the most important is that people have pre existing immunity to AAV, and so a large number of patients can't be treated.
And after the first dose, all patients will develop immunity so that they can't be retreated. That's a big issue with AAV. Another important issue is at this stage, the dose response has been very, very difficult to predict. The approach that we've taken with cell based delivery using lentivirus avoids a number of those issues. So you don't have to worry about preexisting immunity and there's a much better opportunity to control the dose response effect.
It does have its own issues though, which I will touch on in a minute. But in this setting, we harvest stem cells from the patients. We use a lentivirus that contains our gene of interest to deliver that gene into those stem cells. We then expand those stem cells and we deliver those back into the patient. One of the issues at the moment is those patients have to be treated with a myeloablative agent to create space within the marrow for those stem cells repopulate.
And that can cause a lot of difficulties for the patients. So if you can develop an approach that limits the extent of the myeloablation that's required, I think you've got a big technical advantage. So we as I said earlier, we acquired Calimmune about 2 years ago now. And 2 years on, I think the acquisition has gone very well. The company has been integrated into CSL R and D, and we're recruiting for our first clinical study.
What we got when we acquired Calimmune was expertise in know how, but some really important proprietary technology as well. So one was the ability to manufacture lentivirus using this Tegrity system, but perhaps the most important was a Select Plus system, which uses a short hairpin RNA to really give the transduced cells a selective advantage over existing cells within the body. So the ability to reduce the level of myeloablation that's required. So what we're hoping here is that with the use of Select Plus, we can have a vastly reduced level of myeloablation and potentially change this from an inpatient to an outpatient setting. We have this Select Plus technology incorporated into the clinical program that's just about to start and that's CSL200 for the treatment of sickle cell disease.
Again, Diana will talk more about this, but sickle cell disease is a result of abnormal beta globin With the lentivirus, we're looking to replace that abnormal beta globin with gamma globin, which is fetal hemoglobin. You can see the construct there on the right. And we're hopeful that we'll be able to restore normal hemoglobin function. Now, so what are we beyond sickle cell disease, what are we thinking about? And one of the areas that's obvious for a company like CSL with a strong tradition of working in primary immune deficiency is what are the primary immune deficiencies that we can treat with gene therapy and cure.
And one of those is, which got Aldrich's syndrome or WAS. This is a rare immune deficiency caused by a mutation in the WAS gene that codes for the WAS protein. The WAS protein is exclusively expressed in a range of blood cells, contributes to organization of the cytoskeleton and as a result to signal transduction of the migration of immune cells. So people with a deficiency in WAS protein have recurrent infections, microthrombocytopenia or eczema, a range of other autoimmune disorders and are currently treated with IVIG. The only cure for them at the moment is a stem cell transplant.
So we've developed with our new colleagues at Calimmune, a lentivirus vector that incorporates the wash gene. We've been careful about selecting the promoter. We're using Select Plus to give us a selection advantage and decrease myeloablation. And we're moving that program forward in preclinical studies at the moment. So we think that's a really exciting piece of progress for us and extending on what we acquired from Calamute.
I think the interesting thing here is that while gene therapy might be used for some primary immune deficiencies, those rare ones where we understand the molecular basis, it's true to say that the vast majority of immune deficiency patients will continue to be treated with intravenous immunoglobulin because we don't understand the molecular basis of the disease. And in that context, I'd just like to comment briefly on the use of IVIg and return to a slide that I presented last year, just highlighting that point. But also I know that many of you are interested in some of the newer molecules that are coming through that provide opportunities potentially to work in patients where we traditionally have used IVIg. So on the left there, you can see what I've just been talking about where we use Ig therapy to treat patients with immune deficiency to protect against pathogen or infection. And really, IVIG therapy is the only thing that's going to work there.
IG Multimers and FcRn binding antibodies won't work in that space. Efficacy there requires the complexity and the repertoire of the IVIg. You can see IG has a number of other functions, though, across the top, some, but not all of which, are reproduced by the other agents which are being developed. So we're developing CSL-seven thirty in collaboration with our colleagues at Momenta. That's a trimer or a Moltima, and that can impact on Fc gamma expression, can modulate immune cell function, it can probably lead to the reduction in pathogenic IG and it can compound scavenge complement.
FcRn binding agents prevent the recycling and long half life of antibodies. So their mechanism of action is primarily limited to a reduction in pathogenic autoantibodies. So while they will target autoimmune diseases, where it's very clear that autoimmune antibodies are the primary mediators of disease, it's at this stage difficult to understand how they will work in autoimmune disease with a much more complex basis. So to summarize then, in CSL Research, we've been expanding our capacity and capability across our global research sites. We have some fantastic facilities.
We have continued to invest in external innovation to make sure we're competitive and have new ideas to feed through to the clinical group. We're leveraging all of our technology platforms, gene therapy, plasma and recombinant. We're innovating in all of our areas of business strength. We have our 5 therapeutic areas plus flu, and we've got research projects in all of those areas. And all of them are focused on meeting really important areas of unmet medical need.
So I think our focus is on creating sustainable portfolio of early stage opportunities, including gene therapy projects now and I think that's moving along very nicely. So with that, I thank you for your attention. I will hand over to my colleague, Diana Lancione, who's going to give you the first part of the clinical development presentation.
Thank you, Andrew. I have about 20 or 25 minutes with you to give you a bit of a whirlwind tour of a number of diseases where CSL is now progressing different drug candidates. And I hope that this will leave you with the impression that we have, which is that we're very well poised with this exciting and broad pipeline to fuel CSL's growth in the future and to serve different patient communities in addition to some of the patient communities that we already serve. And I'll head right off into showing you a list of what those conditions are. Taken together, one of the reasons it's so exciting is that all of our therapeutic areas are being positioned for future growth for these diverse programs.
And as a portfolio, they also leverage all three of our product development platforms, plasma protein purification, recombinant technology and cell and gene therapy. So let's start off with our hematology and thrombosis program therapeutic area, which is interesting because just in this TA alone, we'll have the opportunity to look at programs leveraging all three of those production platforms. As Andrew mentioned, one of our targets is sickle cell anemia. This is a genetic mutation derived disease where there's a missense mutation of the beta globin gene that leads to a dysfunction in the hemoglobin that is so predominant in red blood cells. And the red blood cells in contrast to normal red blood cells are more fragile, more prone to sickling inside the blood vessels that can lead to a variety of different complications.
The red cells can lice, release toxic contents into the bloodstream and cause a variety of different downstream inflammatory cascades, thrombotic phenomena and vasospasm. Over a long term that can deprive end organs of oxygen they need and lead to a variety of organ dysfunction that taken together shorten the lifespan of sickle cell patients. And it's remarkable that even with all of our modern medicine today that sickle cell patients still only enjoy an average life expectancy of 40 to 60 years, pointing out the major unmet medical need that still exists for these patients. In addition to those chronic complications, patients often have chronic smoldering degrees of pain. And sometimes for a variety of reasons that pain can escalate to an unmanageable level, forcing patients to disrupt their school or work programs and go to the hospital where they can get IV antibiotics and other measures for supportive care.
We call those acute episodes vaso occlusive crisis. They're very disruptive to sickle cell patients. So they have a variety of acute and chronic complications in the disease and that's why it's a major effort for CSL to try to bring new therapies to this space. As I mentioned, we're trying multiple approaches. So the full spectrum of sickle cell anemia is diverse.
You've already heard about at the top our long term goal to provide long term disease management to sickle cell patients through our CSL-two hundred program. This would introduce a healthier version of the globin gene to patients and prevent some of the sickling that causes all of the complications. It's exciting to be in Phase 1 with that program and really represents a major step forward for us with that product development platform. In addition, we have a plasma derived protein, hemopexan or CSL-eight eighty nine, which targets the acute vaso occlusive crisis. And I want to tell you a little bit more about that leveraging off of Andrew's comments earlier.
In the setting of sickle cell anemia, we have those fragile red blood cells that are coursing through the vessels and they really chronically lice and release these toxic elements of cell free hemoglobin, which rapidly converts to cell free heme. Now red cell lysis in and of itself is not abnormal. There's a limited lifespan even for normal red cells. And you and I have that turnover and uptake of hemoglobin and heme happening on a regular basis. Thankfully, in the normal setting, you have molecules like hemopexan to scavenge up that cell free heme, deliver it safely to deliver and as illustrated in the lower right hand panel, help its facilitation and clearance from the body.
However, in sickle cell patients, there's such a more rapid turnover and lysis of red cells that hemopexan levels become depleted. And patients don't have the capacities of a normal patient to clear that toxic heme. As a result, the heme is available to interact with a variety of receptors inside the vasculature and initiate those toxic inflammatory and thrombotic cascades, leading to all of the downstream complications that I mentioned, particularly some of those associated with the acute vaso occlusive crisis. So our premise in this program is that by supplementing plasma derived hemopexan in the setting of vaso occlusive crisis that we could limit the severity and duration of the event and get patients more quickly back to their homeschool and work routines. We're excited to be in Phase 1 with that program and look forward to telling you more about it as it progresses.
The 3rd program that I'm going to talk about in the hematology and thrombosis area is a recombinant protein, garidazumab, our CSL-three 12, our anti Factor 12A inhibitor. This is a really unique mechanism of action and I'm going to speak about it again at the end of the presentation. But it has a position in interacting with a number of different cellular pathways that position it for indications in the antithrombotic space and hereditary angioedema and even other areas. I'll start with the role that it might play in managing thrombosis. There are 2 clotting cascades in the body, one that's initiated by tissue injury, but another that's initiated blood is exposed to a foreign surface.
And we call that contact mediated thrombosis. CSL-three twelve is in a position to mitigate the activation of contact mediated thrombosis. And what really differentiates this from any other anticoagulant approach is that it has the potential to limit thrombosis without adding bleeding risk. This really positions it for a trial of its potential to stop the clots that sometimes form when the blood is exposed to a foreign surface. 1 of those clinical situations is demonstrated on the right hand side of the slide, when patients have central indwelling catheters.
Patients sometimes receive these catheters to get long term therapies of different types, perhaps antibiotics or chemotherapy. The problem is those catheters are subject being a foreign surface to activating the contact mediated thrombotic cascade, forming clots and then causing all manner of complications in patients leading to infection sometimes or removal of the catheter and interference with delivery of the much needed therapy. We believe this is an ideal setting in which to test the potential of Factor 12 to disrupt that thrombosis. And if we can prove it there, we believe there are multiple other clinical applications for this mechanism. Moving on to the respiratory franchise.
Andrew told you about CSL-three eleven, our anti beta common program. And I really want to emphasize that this is a very broad mechanism of action. Andrew outlined for you the potential of it to impact the common pathway of IL-three, IL-five and GM CSF and to impact a very broad range of cells in the human immune system. So it can really address inflammation in a very broad and systematic way. One of the most exciting potential applications of this is in severe asthma.
This remains a major unmet medical need despite the approval of various biologics, because those biologics really only serve a portion of the severe asthma population. They're targeting only some of the cells and pathways that CSL-three eleven can with a single agent. So it's poised to potentially deliver benefit to the entire spectrum of severe asthma, which is not something that any biologic to date has been able to do. We're really excited to begin this program and we're in Phase 1 now. Our plan is to start in mild asthmatics to progress and get our safety and pharmacology worked out and then to demonstrate the proof of concept in severe asthma.
But again, because of the broad potential of this mechanism, we may be in the position of being able to study multiple inflammatory conditions at the same time. Moving on to the cardiovascular metabolism area. While Bill Mezzanati in the second session will cover CSL-one hundred and twelve, I want to tell you about something earlier in the portfolio, and that is CSL-three forty six. This is a monoclonal that binds vascular endothelial growth factor B and prevents it from interacting with its receptor, which is expressed on endothelial cells and in a soluble form. And it's a very unique mechanism of action.
Our preclinical data tells us that it has impact on adipose tissue and on end organs and ultimately prevents the accumulation of toxic fat that contribute to end organ dysfunction. In particular, we've been able to demonstrate a strong database of its protective effects in diabetic nephropathy. And so working with international experts in that disease, we've designed a robust proof of concept program that we'll be initiating within the next few months to demonstrate the potential of 346 in protecting diabetic patients from the progression of kidney disease. This is a very major unmet medical need. I think most of you know that diabetes is unfortunately continues to increase significantly in prevalence.
This data shows a U. S. Point of view, but a similar phenomenon is happening in high, middle and low income countries with rapidly escalating rates of diabetes and with it escalating rates of complications including diabetic kidney disease. Despite all available therapies for diabetes and various protective therapies for the kidneys, we still see rising incidence of this disease. We see no agent that is really arresting or reversing the disease process.
And so it remains a major unmet medical need for patients. We're excited to demonstrate the potential of 346 in this condition and we'll tell you more about that study as it reads out. Now I'm going to enter several programs that are in our immunology TA. And taken together, they represent a diverse set of mechanisms. One targets a particular cell type of the immune system, another targets 3 different severe systemic autoimmune conditions.
And I'll finish out with coming back to the hereditary angioedema space where CSL has been serving patients for a long time, and we continue to strive to bring new benefits to those patients. We'll begin with CSL-three twenty four, which is our G CSF receptor antagonist program. This is a monoclonal antibody that blocks the effects of G CSF, which is a major pathway managing neutrophils, the most abundant white blood cell type of the body. And neutrophils are critical to human health. They participate in many important functions of the body, including fighting infection.
Unfortunately, neutrophil is also featured as a pathogenic cell when it becomes dysregulated and accumulates in different tissues causing destruction, inflammation and general immune dysregulation. And so it represents a unique target for us to go after when neutrophil is a prominent feature of the disease process. It's a 1st in class mechanism as far as we know, and so we're excited to test the potential of it. We've decided after completing a healthy volunteer study to focus on a group of conditions at first called the neutrophilic dermatoses. And these are skin conditions where one of the hallmark features is a sterile accumulation of neutrophils in the skin That's without infection or auto antibodies causing it.
And what you see here in the picture is a picture of a patient with one of these conditions called hidradenitis suppurativa. It shows the armpit of a patient that unfortunately has experienced significant scarring and disfigurement from ongoing neutrophil driven inflammation. This unfortunate disease impacts patients, and it's growing in prevalence, has very limited treatment options available to it and really significantly impacts patients' quality of life as it brings pain, disfigurement, discharge to the armpits, to the groin, to the buttocks and is really a source of major need for new therapy. We hope to show safety, efficacy and get early signals of response in this patient population with the ongoing study. And like the other molecules I mentioned, once proving the concept here, there are opportunities to bring this benefit to other diseases as well.
I'm now going to introduce 3 different systemic autoimmune conditions where CSL is targeting various therapies. The first is systemic lupus erythematosus. This is a disease driven by auto antibodies, which trigger various inflammatory cascades, including interferon and other inflammatory molecules in the body. It's very diverse in its presentation. It typically hits women of childbearing age and some women are not very heavily impacted, perhaps with some mild skin or joint findings.
Unfortunately, some other patients have much more severe and multi organ involvement, sometimes with extensive damage to the lungs, heart and kidneys. And it's those patients with significant end organ involvement that even experience a mortality impact from this. As you can see, only 90% of patients survive over 10 years. It remains a major unmet medical need for patients who are experiencing these kinds of complications. I mentioned interferons as one of the driving molecules and pathways for this disease.
We know that to be true from preclinical work and it's recently been validated in the clinic by other agents. And so a reasonable target to reduce interferons is to try to eliminate the major producer of interferons in the body, that's plasmacytoid dendritic cells or PDCs. Well, we have a molecule in CSL-three sixty two, our anti IL-three receptor alpha molecule that actually binds to those PDCs and then attracts natural killer cells to destroy the cells. So it blocks and takes down PDCs. It also does the same with basophils, which may play a role in the disease as well and that it may propagate the auto antibodies that are part of the disease cascade.
The fact that it's covering not only, interference, but this number of cell types behind that differentiates CSL-three sixty two from other interferon targeting therapies in lupus. And so we are in this stage now where we're designing a Phase I program in lupus patients and pending regulatory review are going to be excited to get underway soon. The next disease I want to cover is systemic sclerosis, again, an autoantibody driven disease with diverse manifestations. The hallmark features are in the skin, where a great preponderance of patients have thickening and fibrosis of the skin leading to various skin based complications, But equally or even more impactful to the patient's quality of life and life expectancy are the involvement of end organs like lungs, heart, kidneys, GI tract. And this is a very, very serious condition where progressive fibrosis of these organs leads to greater and greater degrees of dysfunction.
And with that impact, unfortunately, this is the most life threatening autoimmune condition. And so represents a major unmet medical need, not just to address some of the symptoms, but to really modify the disease. And so we hope to leverage the strength of our IG franchise in this condition. IG has the potential to be the 1st truly disease modifying agent in this condition. And we're starting with the IMPRESS study, which is our trial of PIVAGEN in systemic sclerosis that will give us an opportunity to assess safety, efficacy and the appropriate dosing in patients who will be trialed against placebo, but then everyone will be able to get Privogen in an open label extension.
And because we're eager to test the IG hypothesis, we also want to try to offer patients the convenience of ISENTRA and subcutaneous dosing. We have a trial called the SURPASS trial, where we'll be testing Hizentra and really making sure that despite the sometimes extensive skin involvement in this condition that we can safely deliver IG through the subcutaneous route of administration and again assess the safety, pharmacokinetics and efficacy. Taken together, we have a couple of different opportunities to serve systemic sclerosis patients with our IG franchise. And given the unmet medical need, we're really pleased to be able to begin those programs. We're actually already dosing in the SURPASS trial and should imminently dose in the IMPRESS trial.
The last autoantibody systemic disease I'll be covering is dermatomyositis. This is not an early phase program. It's a Phase 3 program for a condition that's rare, serious, it's life threatening. It also has a mortality impact unfortunately in the 5 year range, as you can see on the slide. It shares some features with the other conditions in that its hallmark features do show up on the skin, as you can see in the pictures, but it also has extensive involvement of muscles impacting both skeletal muscles, smooth muscle in the GI tract and has diverse impacts on heart, lung, even association with cancer.
And this also affects females disproportionately and remains a major unmet medical need. There is a lot of data to suggest the role a therapeutic role for IG in this space. And so we have initiated after consulting with regulators of Phase 3 RECLAIM study that will demonstrate the potential efficacy of Hizentra in dermatomyositis over a treatment period of many weeks that allow us to assess the impact on multiple measures of this disease. And we're very pleased to be enrolling patients in the U. S.
And Japan in the study, well underway to progress the trial as we hoped. Finally, I want to come back to hereditary angioedema. Obviously, this is a disease and patient population that CSL has served for a long time with BARONER and then transforming the space with HEYGARDA, providing them a highly efficacious prophylactic option. We are testing garidazimab of anti Factor 12 antibody I mentioned earlier for its impact on attack rate in hereditary angioedema, because Factor 12 in addition to blocking the contact activated thrombosis I mentioned is also upstream of the pathway that produces bradykinin and which is the central pathogenic mechanism of HAE. In this study, we were able to test 3 different dose regimens and a subcutaneous route of administration on an every 4 week schedule and versus placebo.
We're still interrogating the data from the study. We're very pleased that we were able to complete it in 1 year period of time. So we don't have all the data yet, but we have seen the top line results. And I'm very excited to tell you that it shows compelling evidence of safety and efficacy across all three doses. We absolutely believe this forms the basis of a new potential therapeutic option for HAE patients.
We'll be working as rapidly as we can to get that data to present to you in an appropriate international forum and to work with regulators to progress the program as quickly as possible on these on the basis of these strong results. So very excited to see the further potential of this agent in HAE. I hope I've given you a sense that our pipeline is on the move. We're entering a number of new disease areas with product candidates that stem from plasma, from recombinant technology and from cell and gene therapy. And they're taken together, they position us well for growth in all of our therapeutic areas and to serve more patients in the future than we do today.
Bill will continue later on to tell you more about CSL-one hundred and twenty two and our transplant franchise. But for now, I'm concluding and I will introduce Bill Campbell to the next session.
Thank you very much, Diana. Good morning to all of you in the room this morning, as well as a big good morning to those of you participating online. I'm thrilled to be back in Sydney once again. I love each and every trip to Australia. And it's great to be back sharing the podium with my friends and colleagues in research and development.
What I thought I would do this morning is start with a fairly high level review on the commercial side of the business, give you some interesting facts and figures that will put the business, I think, in context. And then from there, I'll drill down through our IG franchise and provide a bit more color. So on this first slide, I thought I would highlight the commercial team broadly. For those of you that don't know, we're about 1800 professionals across the globe. The team works out of 35 affiliate offices now and we conduct business in more than 100 countries.
On the bearings side of the house, the team generated $7,200,000,000 in revenue last year, and I'll come back to that in a bit more detail. The team and the revenue was arrayed across 4 regions, and I think we've talked about that in the past that we break the world into North America, Europe, typical Asia Pacific alignment and then what we call intercontinental, which is Latin America, Russia and the Middle East. And then as you heard from Doctor. Mazzonati and Doctor. Lancione, we are now operating across 5 therapeutic areas, mostly on the commercial development side.
But I'm going to talk as you heard much more in the traditional way that you heard about the business. So the team delivered, I think, another outstanding year in fiscal 'nineteen. We grew the revenue 11% on a global basis. We're quite proud of that on the bearings side of the business. But not only did we grow the business globally at 11%, we grew once again in a really strong manner across all four of our regions.
And that ranged between 9% 17%. And I take a minute just to highlight that because the regional growth is an area we've been working on over the last 4 or 5 years to really ensure a broad base of growth contribution, not only by product and by therapeutic area, but to ensure that all four regions and all major markets are contributing to growth. We are still executing to, as we call our plan on new products. I'll remind you that we had 5 new launches in the 24 month period that ended March of 2018. So in many, many ways, while these products are still are already contributing to growth in the business, in many ways, they're still very much early in their life cycle.
And I'll spend a little bit of time talking about that. Important to, I know all of you, our IG business, we grew substantially last year. I'll provide a bit more color on that, but for sure outpaced the market both in volume and in share. We opened 4 new affiliates last year between Colombia, Dubai, Saudi and Korea. We think that this is important to continue to expand our footprint to prepare for the future and again continuing to diversify our business.
As you know, I think we spoke a bit about this last year. We acquired our GSP license in China. We're well on our way down that path. We think that this is a really important step for us to take more full control of our business. And we think that there's some synergy and significant growth opportunities in China.
And as we've already spoken about, we spent a lot of time last year really organizing the team around these 5 therapeutic areas. We delivered, I think, strong demand across the product portfolio last year. I'll speak at a high level now and then provide a bit more depth in a couple of minutes. But in terms of the IG business, we continue to see really strong underlying market growth. Market growth that really is at the high end of what we would call the historic growth range, and we think that that will continue for some time.
We've taken a very disciplined growth to our expansion in any new market that we go into. We plan on being there for the duration and we take that quite serious. Our growth was driven importantly by volume. It wasn't price, although there was some price appreciation across the portfolio. Importantly, we also had a very nice growth in terms of Hizentra, so a beautiful mix improvement.
In terms of the coagulation side, we've now achieved market leadership in key markets like the U. S, Germany and Japan. And I'll talk about those in a bit more detail in the second part of my presentation. We are in the early days and you'll hear me say that because I preach it to my team on a very regular basis. We're still in early days with the launch of our new products.
That includes Idelviana and Astella as well. And we have many, many more markets we need to launch in. We are quite excited about a possible label expansion, moving the dosing interval out to 21 days in the not too distant future. In terms of our specialty portfolio, this is an area that we continue to be impressed with. We had significant growth with both Kcentra and Hey Garda.
And I'll talk a bit more about that again in the second part of my talk. And then lastly is albumin. We don't spend a lot of time generally at this meeting talking about it, but it's obviously a critical business for us. We are disciplined in our approach in China, and I think that discipline has paid big dividends. We are the market leader there and remain so.
Much more important though or equally as important to that growth in China is the volume growth that we experienced in every region with albumin last year. And so it's an area that we're spending a bit more time on and had really nice growth with the albumin portfolio as well. Okay. Let me move into the immunoglobulin market now, and I think I've got 7 or 8 slides, and we'll drill down a bit deeper here. This is a market that continues to grow rather substantially.
We saw volume growth of about 8% again last year, and we think that that will continue. We've talked about the growth drivers really on the left side of this slide. Sorry about the look of this slide. I think it didn't translate well for some reason on the right. But importantly, we've talked about the growth drivers on the left.
We continue to see increasing awareness in diagnosis, certainly growth in the PID and CIDP area, and in an area that we've talked a bit about last year and we continue to see rather rapid growth is in the area of secondary immune deficiency. That's largely driven by the CAR T therapies that are out there. These drugs are providing really frankly amazing results in B cell lymphomas, really driving a great result for patients. And we think that that will continue. We continue to, as you saw from Doctor.
Lancone's presentation, we continue to look for new indications and we think we are on the cusp of some of those and that will drive additional usage. As you're all well aware, there were some market tightness last year in the space. We think that will continue. I personally think that, that will last for a bit longer. Having said that, let's turn a little bit to the CSL portfolio now.
This is an area that's of vital importance to us for sure. We grew the business on a revenue basis 16% last year. And I would just remind you that we exited CareMune from the business and despite that grew on the revenue side 16%. We have really strong growth on the volume side for both Privagen and Hizentra in the low 20% range, respectively. We have developed market leading products.
As you'll see, we have the number one product in the IV sector with Privagen and we have the number one product in the subcutaneous space with Hycentra. We did grow substantial on the volume side, and I'm going to share with you in a minute a couple of slides that will speak to the share growth that we saw. Again, I come back to this point of balanced growth across all regions. We think that that's really important to our business. More importantly, it's really important to the patients that need these vital products.
Each of our 4 regions grew last year rather substantially. We don't move the majority of our product into a single market or a single region. We really try this try for this balanced growth. We do have a portfolio approach in CIDP now, as you know, with both Privagen and Hycentra, and we think that that will serve us well. We're certainly hearing very great things about the addition of Hycentra in this space, and I'll share some detail with you in a minute.
And lastly, this is an area where CSL has been involved for the last 40 years. We have a really strong history of innovation. And just before I conclude this part of my presentation in a few minutes, I want to share a little bit of look into that history. Let's talk for a minute about Privagen, and I'll set up our performance slide with this one. Privagen is the number one product in the world.
We're now approved in 87 markets. We're quite proud of that. This is a product that's been on the market now for more than 12 years and has a really broad basket of indications. So how did we do? I think this slide will give you some perspective on how we finished the fiscal year in 2019.
The way to look at this slide is the y axis is share of the IV market only with patients in 7 markets. So this is the U. S, the 5 key markets in Europe and Japan. And I think what you see over the last three quarters is rather strong growth. We added 4 share points across the end of the fiscal year.
I think there's a number of reasons behind the growth. I think 1st and foremost, we continue to execute to our strategy and we spend a lot of time with each of the markets and each of the region heads to really think about and execute to the playbook that we've put in place. It's certainly owing to the performance of new products like Privagen in the CIDP space in the U. S. And Japan, and certainly reflects a bit of our historical investment in plasma collection and manufacturing throughput.
So really excited about the growth in share with Privagen. Moving to Hycentra a minute. This is really one of the flagship products that we have. It's a really vital product and it's a product that we spend a lot of time with. It's the product that innovated in the subcutaneous space.
It's a product that's now coming up on a decade of use. It has more than 6,000,000 exposures worldwide. This is a product that has been, is today and will continue to be the market leader in this growing space. So how did we do this slide? I think will give you some perspective.
It's set up the same with the 7 major markets and on the y axis, the share of the subcutaneous volume and then time along the x axis. And you see again 4 share point gain over the last three quarters of the year. So we're very proud of this effort. Again, I think we are in the early days with respect to our launch in CIDP, but without a doubt, we're seeing some uptake with Hycentra here as well as uptake in conversion in the primary immune deficiency market as well. So we are in the early days of CIDP, but I wanted to take a minute and just talk about that.
And I think as we've said to you, as I've said to you over the last couple of years, there's a number of unmet needs in CIDP, and we think Hycentra addresses those in a really substantial way. I won't spend a lot of time with the slide, but I do want to remind you that we are less than 2 years into our launch in the U. S. And in Europe with this product, less than a year into the launch in Japan. Interest remains really high on these products.
Awareness is growing daily. The CIDP space is a new area in the U. S. As you'll recall, we didn't have the PIVAGEN labeled indication there. So we're still creating awareness there.
Having said that, we've grown both Pravagen and Hizentra share, and I'll share a little bit of information with you in the next slide. And then importantly, as you heard from Doctor. Mezzanati, we just recently obtained exclusivity for Hizentra in the CIDP that exclusivity for 7 years going back to, I think it was March of 2018. So really exciting asset for us. And you see Hizentra shown on this slide in red and some rather dramatic growth across the CIDP space.
So again, y axis now is the same 7 markets, the 5 largest in Europe, U. S. And Japan. And you see over the last 18 months rather dramatic growth. This slide is not just Hizentra.
It is both Privagen and Hizentra. And so you can see we've grown from really the low 20% share in these 7 markets to now approaching 30%. And this data is as of the second quarter of 'nineteen. So I'm really honestly proud of the team. I'm proud of the execution that they put against this early days, still lots of work to be done.
We don't take this for granted. We spend a lot of time to really grow this business, and I think it's beginning to show. So I thought I would leave you with this section of my presentation on market leadership the IG space. As I mentioned, we've been at this for about 4 decades now. I won't go through all of the first that are on this slide, but if you take a moment to look at them at your leisure, I think there's a lot for us to be proud of in terms of bringing the first IVIG to market, the first SCIG to market, the first 20% concentration, the first and only CIDP indication in the SCIG marketplace, etcetera, etcetera.
So I take a minute just to highlight this to say that this is our area of incredible focus, both on the research side, but certainly on the commercial side of the house. And so we're quite proud of this. And I think this heritage will lend itself to further growth as we go forward. So with that, I think what I'd like to do is turn the floor back over to Doctor. Mezzanati, who will now host our first Q and A, and I'll invite the other speakers back up.
Bill?
Thank you. Thanks, Bill, and thanks to all the presenters so far. And now we're just as we're assembling up here, I'll just remind you, if you have questions, please use the mic because we do have people online listening. And so with that, we're all set. And we'll take the first question, which you're raising hand, okay?
Hi. Dave Stanton from Jefferies. Just a very quick one from me for Bill Campbell, please. So you're saying you got orphan exclusivity that's been granted for Hizentra CIDP recently. Are you and then you said it's from March 2018.
Are you saying that it's backdated for 7 years from March 2018, please?
That is correct.
Yes. Yes.
Sorry, it's Andrew Goodsall from MST Marquis. Just a question for Diana around 312, which I guess is now called girdasimab.
Geradasimab.
Geradasimab. Just wondering the extent to which you can talk about how that compares with the other monoclonal antibody that's in the market already, just in terms of attack reduction in PROFIN?
Well, we want to provide you specific answers to those questions, which we can't do today. We are still getting the data, but I can tell you that the top line, we feel this is very competitive and look forward to being more specific in the future. I'm sorry, I can't be more specific today.
And just the follow-up is just target commercial date or the date that you expect to be in market?
I'm sorry, could you repeat that?
The target commercial date, Commercialization?
So the commercialization date will depend on the Phase III program, which we haven't agreed with the agency yet. So we're a little bit away from being able to give you that date.
Okay. Thank you.
Okay. In the back there.
David Lowe from JPMorgan. Just with the new indications that you're targeting with immunoglobulin, I'm not going to try and pronounce them, but SSC and DM, just if you could talk about current treatments at the moment and particularly wondering whether these patients are already being treated with immunoglobulin?
So there are 2 different conditions with 2 different treatment paradigms. One of the reasons we can go into a Phase 3 study in the immune with immune globulin for dermatomyositis is there is some literature around the performance of IG in dermatomyositis. Ours is the first program looking at the subcutaneous administration of IG, which we think will be an important element of the optimal treatment program for dermatomyositis. And so this will be part of why we think this is such a high value add to that space. It will be the first definitive evidence of IG in that space and providing subcutaneous route as well.
For systemic sclerosis, there really are very few limited treatments. There was a recent agent that was approved for the some of the lung aspects, the lung fibrotic elements of systemic sclerosis, but no agent that's really truly disease modifying. And that's why we're excited about the potential of IG in this space.
And if I could just have a follow-up for Bill. Bill, you mentioned the market tightness and you mentioned that you expected it to continue on. I was wondering if you could talk to that and what do you think is causing it and when you think it might continue for a little longer, what are you thinking?
So I think historically, we would say the market broadly is growing in that 6% to 8% range. And I think what we've seen now and if you go back and really dissect the last several years, the growth in the marketplace has been really at the top end of that range. And I think our projections in many ways continue to show that. So I think that's part of it. I think that the underlying demand is maybe a bit higher than what we've seen historically.
Secondly, I think that there's been a lot of movement in the little bit of loss momentum there. And I think thirdly, there's been a number of new markets that have come on and not only for us, but others as well and really being a fairly sizable opportunity and that's taking some additional IG. So I think for a lot of those reasons, I think that there's a number of companies that perhaps haven't invested as much in plasma collection. I think as you know, it's been one of the areas that we've been strongly focused on over the last 4 or 5 years. And we think that that is a dividend that will help us.
Thanks.
Hi. It's Leanne Harrison here from Bank of America. I've got a question for Bill Campbell around what you mentioned around the level of growth in provision and HiCentra in the low 20s. Is that sustainable? Or what's the biggest challenge you have to maintaining that level of growth?
And can we expect that to go higher for 2020?
So I think I wouldn't sit here today and project that that's our growth rate going out over the next several years. I think we were able to grow quite strongly in the last few years. And I think what will continue will be growth for both of those products. The key is for us to continue to stay up with plasma collection and importantly manufacturing throughput for those products. I think expanded indications like what we have now with CIDP will allow us to continue a bit of growth on that footprint.
Having exclusivity in CIDP for Hizentra, we think gives us a position of strength. So there's a number of things like that. And I would also then say the new indications that you heard from Diana as well. And while I don't want to over index on this, I really do believe in many ways our global print and the growth that we've had regionally is a really strong benefit to us that we haven't entered markets and then pulled out of. We have found ways to be, I think, very productive and had significant growth rate across all these markets.
And I think that diversification will only serve us well in
the future. We'll take next question in the room and then we'll go on the phone.
Chris Cooper, Goldman Sachs. Just for Bill Campbell, first of all, you mentioned you were well down that path with the new GSP license in China. Can you confirm you are now going direct in that market? And can you just give us some sense of what the how that's going so far?
So we're well down the path. We have continued to expand our footprint with people and locations there. We've set up all of our back office systems that we need to take on the billing and distribution of our product sales as is we didn't have to do that in the past. So I think we've talked a bit of a bit about a first an impact this year as we ramp up the GSP that will light significantly impact us in the first half. And as we move to the back half, we'll start to see some normalization of our growth there.
And just a quick one for Diana on 3, 4, 6, the VEGF B. Any other applications you're looking at beyond kidney disease at this stage? And just Part B as well, can you just give us some sense of how you're thinking about trial design? You mentioned proof of concept.
So our focus of our program is on the kidney. Right now, that's really where we have the strongest evidence. And we've worked, as I mentioned, with a variety of experts in the clinical trials of diabetic nephropathy to work on endpoints that are predictive of end stage renal disease and rate of progression of disease. So we'll be starting those programs soon. We'll be looking at urinary albumin to creatinine ratio as one of the predictive markers that's been most proven in trials for DKD.
I'll hold your question for a moment and just check if there's a question online. Let's just
Thank you. There are currently no questions from the phone participants.
Okay. Thank you.
Sir? Steve Wain from Evans and Partners. Just a question on the orphan drug status. How will that work for you just in terms of allocating resources given the tightness that currently exists? And is there really any advantage for having that status given the restrictions on supply?
Well, I think the advantage really serves us well as we are the only voice with a subcutaneous product. There's a the majority of CIDP, as you likely know, is being used with IVIG. And so we think that this is a fantastic option. And rather than splitting that up with others that can come into the market, ultimately, we are the sole voice and the sole winner in that space for some number of years.
And we hope across the spectrum of time with some efforts in R and D and yield improvement, we'll be able to
help supply it even better.
And just one last one for me, just on the girdasimab. In a perfect world, if that was to progress and subsequently launch with good results, does that create some obsolescence of your existing prophylaxis treatment?
We don't think so. We think that there's going to be diverse patient types in the HAE environment. Some will prioritize a longer dosing interval. Others will prioritize the highest possible attack rate reduction. And so we foresee the role for multiple therapies for HIE patients in the future.
Thanks. Saul Huttleston, UBS. Just a couple of questions. First one, just with haptoglobin, I wonder if you can give us any insights into what the yield might be from plasma at the moment and what dosing might look like for subarachnoid hemorrhage?
I can't give any specific details, but we have done an analysis which indicates to us that supply won't be an issue should we get to that point. And in terms of dosing, it's really a one:one ratio with the amount of hemoglobin that's released. It's a dose that we can deal with and it might vary from patient to patient.
We're still in pretty early stages of the product development with that. So we'll have some more information over time, I think.
Sure. And just one more CSL-three eleven. So targeting asthma initially, but, Don, you mentioned potential multiple inflammatory conditions could be targeted. What would some of those could some of those be?
Well, I think I mentioned severe asthma. Andrew Nash highlighted the potential in nasal polyposis. There may be other respiratory conditions like COPD even. So there's a variety of them. We'll be exploring those in preclinical studies and with consulting with experts.
And any potential for other conditions like rheumatoid arthritis or inflammatory bowel disease?
We're not contemplating those at the moment. But again, this is a very broad mechanism of action. We have a robust program looking at potential new indications, and our focus right now is on the respiratory tract.
It's John Deakin. John Deakinbel, Good morning. Just a question to elaborate a little bit on the gene therapy program that you have. I'm just trying to understand, obviously, most of the nearer term competitors who are close to filing are using the AFE approach.
What are
the kind of time frames for you to understand whether you can be successful in the lentivirus approach, kind of a no go time frame going forward to overcome the limitations you mentioned about that the Myelo ablation approach?
So most of the programs one of the major differentiators is if the issue lies with the circulating blood cell populations, then that's relatively easily addressed care of the lentivirus approach where you're treating the blood progenitors and then they mature into the different blood cell populations. With AAV, you're targeting different organs where the production of the protein normally occurs. So for example, in the liver or in the brain or in other tissues. So there's a little bit of crossover, but not too much crossover, I would say, in terms of indications. For the myeloablation, there are a range of strategies that are being pursued.
There are nontoxic molecules that are being developed for myeloablation. We're certainly keeping an eye on that space. But ultimately, we feel that with a process like Select Plus, whether you're reducing toxic myeloablation or combining it with nontoxic myeloablation, it will still be an effective part of the process. So it will still give the cells that we can select a benefit and an advantage.
Maybe just a follow-up from Bill on the commercial aspect of the gene therapies. I think one of the competitors has filed the hemophilia A product in Europe. My understanding is there's still no agreement from the funders about how the payment these products is going to take place. Can you just give us your thoughts generally on that? And in the future, hopefully, you'll have the same issue.
Yes. No, I think you're broadly right. I think not only in Europe, but I think even in the U. S, payers are struggling with how are we going to pay for these really remarkable breakthrough products. I think the model that you're seeing being discussed by companies like Bluebird in particular, I think are probably a valuable model, Really looking at setting this up over a multi year payment scheme, assuming the product continues to deliver to the efficacy promise.
So I think it's an area that's I think there's a lot of us looking at how to tackle it. We're having discussions with payers across the globe. And I think many, many are in that same ballpark. And I think, if you go back and you look at the discussions, in particular, I think Bluebird is probably the most advanced. I think that that's a reasonable approach.
And I think we're seeing a lot of payers sort of align to that as well.
In the back?
Good morning. Sean Larmen from Morgan Stanley. On CSL-three twelve, I wonder if 2 parts of the question. First part, could you help us understand the commercial opportunity on thrombosis against HAE? And the second part, just the decision to go the HAE target as opposed to thrombosis first?
Well, I'll let Bill Campbell comment on the commercial opportunities. But look, HAE is a patient community we're passionate about. We know this community. We know the needs that they have. And so that was a very high priority for us to continue to try to serve that patient population.
One of the reasons it got out ahead at first. I suppose the other aspect that we can say about contact thrombosis is that we're still working with experts to understand exactly how to optimize the value proposition. We know that there's a lot of thrombotic and bleeding complications for patients who are exposed to foreign surfaces through medical devices and procedures. And so it's a space that we know less about and we're learning more about and one of the reasons why we want to do it right and why it's a little bit behind the HAE program.
And I'm
not sure I'd add a whole lot more on the commercial side. These are earlier stage assets. I think is some miles to go. And I think the clinical benefit will have to continue to mature a bit. Clearly, as Diana said, the HIE space is one that we've been in for many, many, many, many years.
It's really important to us. We've been quite successful with products like Barinert and more recently with Hey Garda. It's an area that is still expanding for us. And I'll talk maybe just mention that we've been a bit supply limited with Hey Garda, as you know, and wanting to ensure that every patient that received this product continued to receive it, never went without. We're quite proud that we were able to manage that with a product that had extremely rapid uptake with new volume of supply coming on now.
We're looking forward to new launches, continued growth. And I think products like 312 will just continue to fall into that vein.
And I would just add, we don't stand patent. And I think that's what you see in a number of therapy areas. Where we have a therapy, it doesn't mean we're satisfied and we stop. And we continue to look at ways to even improve therapy. And we listen to our patients all the time.
And so we continue to try to meet every need of the patient we can. Somewhere in the middle, I think.
Yes. Gretel Jen, your Credit Suisse. So just on the time line for the R and D portfolio, can you give some indication in terms of when you expect to get some top line data on some of the key trials that you talked about today? So particularly the Primagen, Hizentra, IMPRESS, the past trials, CSL-two hundred, CSL-three forty six?
So I think right now we don't have exact timelines for you. Many of those probably will not be in the next year. It will probably be in the year after that is my guess. But some of that depends on recruitment and again, some of the things that are not necessarily in our control all the time.
And then just one for Bill. So just on those share gains charts of Pravigen and Hizentra, do you expect kind of that rate of share gain that you experienced in FY 2019 to continue or do we expect that to kind of plateau in FY 2020?
It's a bit hard to tell yet. The data lags, as you know, is a bit late in the space. I don't really want to foreshadow growth for the current fiscal year at this point in time. I don't think Mark would appreciate that. But I would say these are hard fought wins.
We fully Privagen and the Hizentra front. And we're doing a lot to ensure our sustainability in the area for many, many years to come.
Okay. I think with that, I'm going to we have one last this will be the last question and then we'll go to a break.
Thanks. It's David from Macquarie. Bill, you just mentioned potential for an increased uptake of Hizentra in the PID market. Just wondering what the split where the split currently sits IVIG versus subcu at the moment?
Yes, it still is predominant IV for us, if that's what you're asking about for the CSL portfolio. It's we've been in the IV space with CIDP for quite some time, as you know, outside of the U. S. And then within the U. S, there was a bit of organic use before launch.
But for sure, the split is predominant IV. We're still early days with Hizentra.
Okay. I think we'll have to stop there and take a break. I've got just about 10:48, 15 minute breaks. So we'll come back just a couple of minutes after 11 and start again with the second half of the presentation. Thank you.
Well, welcome back, everybody. We'll continue. I apologize for my voice a little bit.
It's difficult for a commercial person to be standing up here and not having
jet lag and being wide awake at 3 am this morning, my typical Australian sleep patterns for a week or so. Well, welcome back. As I said, I'll continue with the second part of my presentation. I'm going to really just focus on hemophilia for a couple of minutes and then touch on a couple of our key specialty products, in particular, Kcentra and Hey Garda. So with that, let me touch on the hemophilia market in particular.
This is a market that you know is quite large. It's about $12,000,000,000 in revenue last year. Much more important though than the revenue is that this is a segment that's witnessed some significant new technologies and new Just broadly on the hemophilia A space, Just broadly on the hemophilia A space, it's an extremely competitive market. I think you all know this segment quite well. We've seen many, many new products over the last 5 or 6 years, and we'll talk a little bit about our performance there.
Products like Adelvion in many ways have transformed the treatment of hemophilia B. I'll share a little bit of data with you. We are really excited about products like Adelvion. And again, while still a bit early, has performed really, really well. And an area that we don't talk a lot about is von Wilivron disease.
It's a bit of an underserved market, and I'm going to come back to that in the next slide. So this is a truncated version of our portfolio in the hemophilia space. We saw a bit of headwind in the space overall last year as we reported, I think hemophilia or the COAG business being down about 3% last year, really owing to the decline in the plasma derived segment of our portfolio. Having said that, the new products, Idelvion and Astila grew substantially last year, 40% and 85% growth, respectively. These are products that have really terrific profiles and we remain quite excited by them.
Both of these markets or both of these products are still a bit early and we expect to open up a number of new markets for these products this year and years to come. So quite excited and in particular really excited about Idelvion. And we talked a little bit earlier today, or we've talked about it in the past, the potential label expansion to move dosing intervals out to 21 days. You will also recall that we've been in the heme A space for quite some time with both plasma derived products and recombinant products. We did phase out completely HELIX 8 last year and have replaced the margin generated from that with Astella and will continue to grow.
We haven't spoken a lot about the Von Willebrand disease segment in the past, as I mentioned. We do have a market leadership position in the space with the products like Humate in the U. S, Hamata in Europe and a product called Vodcento. These are largely the same products. They are plasma derived products, but these products have derived a bit of growth last year, collectively adding about 7.5% on the revenue side.
We do have about a 59% share in the global Von Willebrand market. It's an area that we've been focusing on a bit more in certain markets. And it's an area that provides a bit of buffer to our broad plasma drive segment. So I thought I would share one slide on Adelvion with you. This is a similar slide to what I shared with you on Privigent and Hizentra earlier.
The Y axis is patient share. This is in 5 core markets. So U. S, Japan, Germany, Italy and the U. K.
There are 5 markets where we have approval, we've launched and we have reimbursement. So it's a bit of a different country mix, but it's these are 5 large markets and I wanted to kind of highlight them for you. You see Adelvion in red and you see that we've grown trajectory. I don't show all the other markets. We have other markets like Switzerland, where we're quite proud.
We have about a 60% share in Switzerland, but a much, much smaller marketplace. So really good success with Idelvion and still many new markets to come in the year ahead. I'm not going to spend a lot of time on Astila this morning. As I said at the outset, this is a product that has a really good profile. It has a competitive profile.
But this is a space that's highly competitive, I would say, in many ways saturated with products with many new products on the market and potentially coming to the market including gene therapy. So our team works every day to try to carve out our respective share in the Hem A space. It is a good profile and we'll continue to fight the good fight with Afztila. I'm going to switch and spend the next 5 or 6 minutes or so really covering a couple of products in our specialty portfolio. This is a product made up of the products that you see on the left side of the slide.
We grew about 6% overall in this portfolio last year. And I think in many ways that masks a lot of really incredible success we had with products like Kcentra and Hey Garda. So we had a bit of headwind last year with Zimura and RISPRISA with respect to some manufacturing challenges. Many of those are now behind us and we'll look to recoup lost business as we move through the rest of this fiscal year. So let me spend a couple of minutes and just talk about Kcentra first and then Hey Garda and then I'll wrap up.
So I tried to give you a little bit of context with where we stand with Kcentra. This is really data focused on the U. S. Market. We sell this product globally and have for quite some time, but I think we've spent a lot of time talking to this audience here about our uptake in the U.
S. So what you see on the left side of the slide in the pie chart in yellow is the proportion of the anticoagulant market that's represented by warfarin. It's still a bit over a third of that market. That translates into the middle part of the slide to about 1,600,000, 1,700,000 patients. And as you see on the far right side, our share breakout versus fresh frozen plasma.
So while we've gained share in the space, we're about a 45% share there versus the 55% or so for fresh frozen plasma. And I We have had really strong growth. I think over the last 6 years, we have orphan exclusivity here, as you know. Therefore, remains the only FDA approved 4 factor PCC for reversing patients. On warfarin and you see the relatively rapid growth that we've achieved on the right side of the slide.
We it doesn't show it here, but we grew volume in the U. S. Now in the mid teens last year. So down a little bit from where we've been historically in the 20% to 30% range, but a far bigger base of business. I'm going to just spend a couple of minutes on Hey Garda now.
We're really excited about this product and have been so since the beginning when we saw the incredible clinical results that our R and D colleagues delivered to us. This is the number one prescribed product in the U. S. For the prevention of HAE tax in the prophy space. We've been in this market and C1 has been used for more than 3 decades.
The profile, I think you know quite well by this time and this profile has truly transformed patient care. And I'll bring that to light in the next slide. So what you see in this slide on the left side, these are the number of prophylaxis patients as we have visibility into. And what you see for 20 sixteen-seventeen, just before we launched Hey Garda, there was just under 1300 prophylaxis treating patients. We launched Hey Garda and the number of patients being treated on a prophy basis grew substantially.
That continued again in 'eighteen, 'nineteen, largely because of Hey Garda and then more recently TaxxYRO. So we've seen about a 40% growth in the number of HAE patients being treated with a prophy regimen. Hagarnd is the market leader, as I mentioned. We went from 0 to a 50% share year 1. We continue to be the market leader in the space.
We had that rapid uptake with significant brand loyalty. Patients do really, really well on this product. And their providers really like this product and see this product works exceptionally well and patients simply don't have attacks. As I mentioned maybe a bit earlier, we have been somewhat limited geographically in terms of expansion. With that new volume now coming online, we're looking forward to launching AGRDA in Canada and Germany and a number of the European marketplaces.
So quite excited about our growth in the space. And again, we continue to be the market leader. As I've done in the last couple of years, I wanted to share a couple of new quotes with you. I won't read the specific quotes, but it gives you a sense both from the patient side as well as the provider side. These patients really like this product.
They've been on the product. It doesn't result I mean, it blocks and patients don't have attacks. It's a natural therapy. It's replacing what's missing or dysfunctional for patients. And as you can see from a number of the providers, patients are controlled and they simply don't want to switch.
So having said that, let me sort of end my remarks here with really kind of where I started. In 2019, the commercial team delivered a really strong year for the organization, growing revenue at 11% clip. We've developed market leading brands, not just with Hey Garda, but across our therapeutic franchises, products like Adelvion and Privigen and Hyzentra, Hey Garda, Kcentra. And we think that development of these brands will continue to serve us well for well into the future. We delivered substantial volume growth last year and I think that makes CSL a bit unique.
We while we had some price appreciation in our base IG business, our business is largely growing on the back of volume growth. And you saw the share gains that I shared with you on the last few slides and earlier with IG. We do have this balanced regional approach. I'm quite proud of that. I talk about it on a very regular basis.
And again, I think it's important as a source of diversification for us globally, just as our portfolio of products provide a source of diversification. And our new products, while still early in their lifecycle, are contributing substantially to the growth of the business today and will continue to do so for the foreseeable future. So with that, I'm glad my voice sort of held up. I'm going to turn the podium over to Doctor. Russell Vassar, Head of our Securus R and D organization.
Russell?
Thanks, Bill. So for a bit of a change of pace, I'll focus on the progress we've made in the Securus portfolio and what we're planning to do over the next few years with regard
to influenza vaccine.
So just to level set, this is the current portfolio, the major elements of the portfolio. We've talked to you about our enthusiasm with regard to transitioning to cell based vaccines. But to be clear, egg based influenza vaccines still are very important in our portfolio and the industry. Our 2 standard egg based vaccines are Afluria and Agripal, 4 strain and 3 strain vaccines. Our standard cell culture vaccine is Flucelvax.
And these are generally indicated for people for the broad vaccination population, what we refer to as standard risk people. For people who are more at risk of influenza, whose immune systems are weakened, we have FLUAD, which is an adjuvant, MF59 adjuvant, which is essentially an immune stimulant, which makes the immune response much more powerful in those more susceptible individuals. And we're talking about older people at the moment, 65 and above, but in the future, might include a pediatric or infant population. And just to point out something many of you, I think, understand is every season, we make a under a great deal of time pressure and volume pressure, we make a seasonal vaccine, and it's essentially a dry run for the event of a pandemic. Without that seasonal season in, season out cycle, we'd never be prepared for a pandemic.
So it's a very important part of the world's preparedness. So just thought it'd be worth seeing the progress we've made over the last 12 months. It's been very pleasing. It's really been a continuation of the work we've described to you previously. Afluri, we've finished the development program for the 4STRAME product with approval down to infants in Australia.
Through Cellvax, we have achieved our first registrations outside of the U. S. In Europe in the middle of the year and then only a couple of weeks ago in Canada. And we have the first readout of the pediatric program that's been part of the BOST marketing requirement of the U. S.
As we aim to get down to the 6 month indication. Those data, a bit like the data you heard with 312, we've just seen the first elements of the data, but we're very pleased that the study met all its endpoints. And those that information, we presented at the appropriate scientific forum in the near future. Fluad has been going well. We continue to gather data on the effectiveness of the vaccine, and it continues to encourage immunization recommenders like those in the JCVI in the U.
K. To keep preferencing FLUAD for older people. And the 4th strain vaccine, which we've been which had been under development, FLUAD vaccine, has now been approved in Australia, and we've submitted a dossier into the Europe. We've had a submission of the dossier for the pre pandemic, the adjuvanted cell culture bird flu vaccine, which is really a finishing off of our preparedness around the Holly Springs plant, and that was submitted to the FDA. And we've commenced a project combining the adjuvant and the cell culture antigens.
We refer to this product at the moment in the shorthand of AQIVC. And that will ultimately replace FLUAD in the market. So I thought it would be worth just level setting a little bit just to go through the areas we focus on with regard to manufacture, the impact of flu in the market and some of the challenges that are faced by the industry in influenza vaccination. So here is just a slide showing on the top, just the standard way we make the flu vaccine that was described actually about 7 years ago by McFarland Burnett here in Australia, which was the ability to grow virus in eggs and in embryonated chicken eggs, and we still do it today. And that process takes the wild type virus as nominated by the WHO about 9 months before the season starts.
We put it into eggs. We generate a seed from those eggs that then comes to the manufacturers and we put into manufacturing. We then grow the virus, purify it and make the vaccine. The nominated virus goes into mammalian cell culture, and then the seed is selected that then comes to us for industrial manufacture. Now the seed that's chosen, either the egg seed for eggs or the cell culture seed for growing to cell culture, is selected based on its similarity to the wild type virus that is predicted to infect people in the next season and its growth properties.
And for egg seeds, we've found, and I'll speak to that shortly, that the virus has to undergo some changes to be able to grow efficiently as well as closely as possible match the wild type. Because we take a virus that's learned how to grow in humans as a nominated virus, it doesn't have those same ecological pressures to be able to grow in mammalian cell cultures. So there's none of that change in the way the virus looks. And just to exemplify that and show you some of the challenges we face in influenza vaccine every year, this slide tries to demonstrate to you the major challenges that we face. So flu vaccine, as many of you will be aware, is a 4 strain vaccine on the whole now in most countries.
2As, we refer to them as H3 and H1. 2Bs, Victoria and Yamagata. And in one of the most important challenges we face, that adaptation of the virus to be able to grow in eggs, over the last probably 10 or 12 years, we've started to appreciate more and more that with the H3 strain, it undergoes a significant adaptation to be able to grow in eggs as well as be reasonably matched to the wild type to the point that it's now looking it has some very important differences in the way the body sort of the immune response of the body generates. So we refer to that as egg adaptation, which does not occur with virus grown in our MDCK cells. The second way that the vaccine can be challenged by the way the virus behaves is actually what we've traditionally known is that the virus mutates every time it infects us and then jumps to another person, it's constantly mutating.
And sometimes it doesn't mutate a lot, but sometimes it mutates enough for the virus that is infecting people in the next season. So there's about a 9 month gap between when we make the vaccine and when it's distributed and vaccinating people. It's different enough to be not matched to any of the vaccines. So it's not usually more than one strain, but it can be a mismatch in the environment of the vaccine. So none of the vaccines are going to address that problem.
And then the last on the right, the last example there is when the virus shifts completely, and that's what forms a pandemic when there's a completely new virus that comes in. And that's obviously a different issue altogether. So it's worth having a look, just stopping and seeing what the impact of influenza is in our communities each year. And these are data that are very nicely collected and presented by the Center For Disease Control in the U. S, the CDC.
And just to take you through, to orientate you, the orange line relates to the left y axis, and it's a number of cases of flu that are picked up each year. The blue bars are the number of hospitalizations that relates to the right hand side y axis. The circles show the proportion of which strain causes how much infection each year, and then the bottom line is the number of deaths. So a few observations. One is that you can see every year is different.
And you can look at you can try and sort of compartmentalize things into by one of the attributes. And I'd say the observation here I'd give to you that 'seventeen, 'eighteen was a severe season, almost in terms of hospitalizations and deaths, almost as severe as the pandemic year of 2,009. Last year and a few years before, you can see hospitalizations were all about the same, that we sort of see that as moderate, and then there were some mild years. But within those years, the strains causing preponderance of infection and the number of infections still varies. So it's quite a complex matrix that we observe every year.
And there is a well accepted saying that in the flu space, which is once you've seen 1 flu season, you've only ever seen 1 flu season because the things change so much every year. But despite these obvious the big health impact, if we didn't have influenza vaccine, it would be much greater. And so this slide shows the effectiveness we is observed. Again, U. S.
Data, because it's very nicely collected and presented. It does tend to reflect what goes on in other countries. And this is the on the left hand panel is the blue bars is the effectiveness of the flu vaccine over the last 10 years. And again, it tends to wobble around a bit. It's not as effective it's not consistently as effective as we'd like it to be.
There are things that impact upon the effectiveness. 2 years ago was the egg adaptation in a year dominated by H3N2. Last year, in fact, there was a late upsurge of the same strain, but instead of egg adaptation, there was actually a mismatch due to the virus mutating in the environment. And so all the vaccines didn't perform so well against that particular vaccine against that particular strain. And the right hand panel is a snapshot of effectiveness according to age, just to try and show that some age groups are more susceptible irrespective of vaccination.
The older kids, the 9 to 17 group, is a bit of an anomaly compared to historical data. But what is consistent is the other age groups, in particular, that older people do suffer most from influenza despite the current vaccination strategies. So for me, the importance is here that there's too much variability more variability than we'd like to see in the effectiveness of the vaccine. Of course, absolutely, we'd love it to be closer to 90% if we could, but not to take away that this isn't still a very important public health measure because flu is so prevalent in the community. Even with these this variable effectiveness, we still see a very important reduction in hospitalizations and death due to vaccination strategies.
So what in terms of the technologies we have, how do they address some of the challenges around mismatch, around egg adaptation, around weakened immune systems. How does our technologies address this? So this is a diagram that's referred to as antigenic cartography or mapping. Essentially, it shows how similar a vaccine or viruses are to each other. And it's described the principles for you.
So here is the picture of the virus is how it sort of matches, let's say, with H3 against the egg vaccine. It's not exactly matched. It's not mismatched completely, but some of the time, it's not going to be particularly effective. And the other viruses, Wolf strains, will be much more towards the center of the egg vaccine antigenicity. The MF59 adjuvant boosts up the immune response.
It's what we do to combine it with in the product FLUAD. It also does something else, which is broaden the immune response. So the immune system, in response to FLUAD, sees slightly broader sort of strains than it currently would with the strains that are in there. So if there's a little bit of change in the virus, it will pick that up and the immune system will respond. So it helps broaden the body's ability to see the flu virus if it hasn't changed too much.
Talked to you about the Cell C being a better match for H3N2 and for any other egg adaptation that might occur, but being clear, it won't be it won't help in the event that the virus mutates in the environment. And then we are doing the obvious thing I mentioned before, we're going to add the adjuvant to the cell strain, and we've just started formulation development this last year. And that will become the best combination of our technologies we could bring in, and we'll ultimately we ultimately aim to replace FLUAD for older people. And we're going to target a slightly broader age range, 50 and above. And we think there's also a role potentially in infants, 6 months to about 5 years.
So what about the EBIT? Where are we up to with regard to understanding those other products, Fluzelvax and Fluid, with regard to the performance in the market? So I think now we talked to you about the initial information we had around flu with Cell Vax last year and cell based vaccines from that season where '17, 'eighteen where that was a particular problem. A couple of points. One is that the basic scientific data, understanding exactly what that egg adaptation change is in the virus that grows up in the vaccine is really well understood now.
There's more studies that are being published, more basic science. And I think within the scientific community, it's an accepted scientific fact that that's a real problem for egg based vaccines and that the cell based vaccine does not have that issue. We presented some preliminary real world data, so nonclinical trial data last year from a pilot program that we've established, showing a reduction in outpatient related influenza vaccine, influenza in people who received Flusilvax versus those who received egg based vaccines. That's we've now got fuller data so we've now submitted for publication a full report from that observation. It's under review at the moment in the journal.
Other papers have come out, one looking at flu related hospital visits from Medicare MedicaidMedicare, full publication showing reduction there in people who receive flu cell based vaccine versus egg. And then a really interesting but not statistically significant observation that's published from another health care provider in the U. S. From that same season, showing quite a substantial reduction in H3 related hospitalizations in that season. So lots of observational data that supports the initial observations that a cell culture vaccine, in some circumstances, might be very beneficial.
There's also now we're seeing quite a pull from the public health experts and from government now saying, We'd like to see a transition away from egg to more modern manufacturing platforms. And this was greatly exemplified by the executive order out of the White House that was released in about September. And that's really calling for more funding without identifying how much and the mechanism, but more funding in public private partnerships into transitioning America away from egg based reliance upon egg based vaccines into new technologies that might be faster and more effective than we've had before. And we've certainly been working with BARDA, the Biodefense Advanced Research and Defense Authority, that's part of American HHS, to help them with our view of what a response would be to that executive order. And there's a process being undertaken at the moment, and I guess it will read itself out in due course.
We've also we also had been looking at the real world evidence for FLUAD. And FLUAD's in a different position to Flussilvax. It's been on the market in Southern Europe for 20 years, and it's been around, obviously, in a number of markets for quite a while. So we have quite a body of data with regard to the performance of FLUAD in these sorts of real world evidence settings. And there were 3 studies data from 3 studies that have been made available this year: 1 from the U.
S, 1 from U. K. From single seasons and then a 15 year observational study from Italy. I've listed the publications here. You can go to them.
They all point in a similar direction. The numbers themselves, I've put them up there because these are the data, but you've got to be careful. The methodology in over interpreting, the methodology is different, and the seasons are different and the endpoints are different, but they all point to the advantage that FLUAD has versus nonagulanted egg vaccines in older people, 65 and above. And you can see here, even in the 15 year experience, there's quite a substantial reduction in hospitalizations in that population of people in Southern Europe. These are the best data we have at the moment, and they're compelling enough for regulatory authorities and or sorry, for recommending bodies to utilize to keep recommending FLUAD preferentially for people who are older, 65 and older, in the U.
S. And U. K. And Australia. And in those latter two countries, we are the sole this is the sole vaccine recommended and used for those older populations.
And it also encouraged the TGA here in Australia to undertake a rapid review of flu add 4 strain flu add vaccine and be the 1st geography in the world to approve that vaccine. So just a word on real world evidence. So real world evidence, we as I mentioned, we had a bit of a pilot program last year to see how it worked for us and how well we could utilize it. We've been very encouraged by how well that's been received. Public health authorities and immunization recommending bodies are really interested and follow this with great intent because of the very that variability I showed you in the way flu vaccine works each year.
And it helps guide them beyond those initial signals of randomized trials. The randomized trials, to be clear, are the highest level of evidence, but they are a small group of people. They're quite a homogeneous group of people, and they're only over a couple of seasons, whereas people, the recommending bodies are really interested in longer term view. The regulatory authorities are getting more and more interested. The FDA released a framework for thinking about it.
But at the moment, in the flu space, they don't have enough confidence in the quality of data to understand how that might influence regulatory decision making. However, we I think it may well occur in the future, but nevertheless, we're taking the responsibility of understanding how our influenza vaccine is performing in the market by strengthening up our real world evidence capabilities And from an outpatient third party contracted effort, we've now started to bring a lot more of that capability in house with programming and analytical capabilities, strengthening out the data set. So we have a lot bigger look at anonymized data. It's going to increase the number of people we can assess by that tenfold. Those numbers in the circles that relate to the number of people receiving vaccine.
And in the near future, we're hoping to be able to include hospitalization inpatient data. So we will be able to gather the whole health experience each season of what happens to people receiving our flu vaccines versus other flu vaccines. So that's a really exciting but long term effort that we hope will we're pretty comfortable it gives us a very good understanding of the performance and the benefits that new technologies will bring. Look, one thing, and it was touched upon by Bill early on that I think is very relevant for Securus, as it has been for the plasma organization over many years, is that focus on quite a narrow space gives us the opportunity and the drive and the motivation to really understand how our business works. And I think the cell culture manufacturing process is very similar to plasma conceptually in that there's an opportunity for an ongoing cycle of improvement.
And we look at our manufacturing process forensically, and we have a very good understanding of how we might improve beyond that step improvement we made a couple of years ago that was implemented in last year's Northern Hemisphere campaign. And we see lots of opportunities for improving the growth of the virus, so how much vaccine we can generate or virus we can generate and then how well we can extract it downstream. And we have a program now looking at that and stepping out improvements over the next 5, 6, 7 years. Another part of that is the seed we put into the vaccine is a determinant of how well we can make the vaccine as well as how well it performs. We have identified a number of ways in which we can innovate to reduce the inconsistency of manufacturing yields as well as speed to the manufacturing and as well as the consistent keeping the accuracy against the wild type vaccine the wild type virus.
And look, finally, just a word on the dynamics of what's going on in the market. There are about 500,000,000 or 600,000,000 doses of influenza vaccine distributed globally. About a quarter of that is in the U. S, about 150,000,000 doses taking into account returns. We don't see a big volume growth over the next 5 to 10 years.
The volume growth that will occur will largely be related to people entering the older age groups where there is a preferential recommendation and a more general a higher uptake of vaccine than in the general age groups. We don't see a big change in vaccination practices in terms of volumes and greater uptake, so just to be clear. The global market is estimated about $4,000,000,000 at the moment. Over the next 10 years, we see that growing quite substantially, maybe 50% -plus or more, largely driven, though, by an uptake of these tech new technologies, ours and others, I guess, for differentiated vaccines around non egg or cell based susceptible age groups, largely out of the U. S, where there will be some premium pricing recognition for the innovation.
And that will drive a bigger volume growth a bigger value growth than the volume growth we might predict otherwise. Just to be and one thing we do know for sure is, yes, the U. S. Will drive growth. The uptake in other markets will be quite variable.
According to the economic advantages that they perceive in new innovations in flu vaccine and their ability to pay. But I do see, over time, transition towards these differentiated vaccines. So finally, next the next 12 months, we'll see much of the same. We'll get approval for we're anticipating approval for Lusilvax in Australia. We submitted middle of this year.
We'll start to get the first clinical data that moves towards approval in infants in the second half of next year. Fluad quadrivalent, we expect to see approvals in the U. S. And Europe. We'll get approval for our pre pandemic vaccine.
And the AQIVC program will go into Phase II development in the second half of next year. And I'll hand it back to Bill.
Thanks, Russell. So you've heard a lot about a lot of programs today. Let me tell you just about a couple of more and then we'll wrap up. So I've talked before to this group about our move into transplant and why we see it as such a strategic opportunity for us, including the fact that we have some of our own therapies we think can work in this space. So one of the areas we've been focusing upon is graft versus host disease.
And that's a devastating complication for patients receiving allogeneic bone marrow transplant, a potentially life saving treatment on its own. But when you develop GVHD, which happens in about 50% of patients, mortality can be up to 70% to 90%, both from this disease of this transplant attacking the patient or from the immunosuppression tried for unsuccessfully generally to reduce the GvHD. We have some preclinical evidence and some pilot data showing some benefit for Alpha-one antitrypsin in the treatment of this and this deadly disease. And so we are taking 2 approaches to try to create benefit for patients with this problem. So first on top is CSL's own internal program.
The title of this study is MODULATE. And that's an alpha-one antitrypsin treatment for actually GvHD prevention. And this is the Phase twothree study I mentioned before. And here on the left is Part 1, where we are going to do a dose finding in an open label fashion over 3 cohorts. And then we'll go into a double blind treatment with a specific dose that we've identified from Cohort 1 I mean, from Part 1.
We finished the 1st cohort and we're actively recruiting. All the sites are up and going. And we're continuing to make progress there. Below is a study in treatment of GvHD with Alpha-one antitrypsin. This is being conducted with our drug, however, by the bone marrow transplant clinical network, which is a North American consortium, so about 25 centers running this study.
So here they're looking at patients who already contracted the disease and whether Alpha-1 can ameliorate or at least reduce the symptoms of that deadly disease. And that study is really in study startup and we anticipate the first patient being randomized any day now. They are I said using our drug and also referencing our IND and in return, we'll get to use these data in a regulatory filing if successful. Both the prevention and the treatment have achieved have been given orphan drug designation by the FDA for the treatment. So the other focus in our transplant area has been antibody mediated rejection.
I've talked to you about this before. The pathogenesis the pathognomonic feature is the development of donor specific antibodies by the recipient. It happens somewhat later in the post transplant period, not in the first couple of days, and has a progressive decline in kidney function and ultimately, unfortunately, loss of graft or loss of life. There are no true approved therapies in this area. However, there are pilot data using C1 inhibitor and pilot data using an anti IL-six antagonist, tocilizumab.
What we've done is we've taken this approach of looking at antibody mediated rejection and through the science understand that there's both a complement dependent and a complement independent pathway for which these donor specific antibodies work. And while unfortunately today there's no clinical biomarker, so you can't predict upfront who has which, we do know that both are in play. And so there are actually 2 studies ongoing. First is our study with C1 inhibitor, the ARMOUR study. This is a study in treatment resistant semi acute antibody mediated rejection, and that is ongoing and recruiting and also has orphan designation status.
Similarly, Vateris is running another study, the IMAGINE study, and this is a placebo controlled trial in chronic AMR using their anti IL-six clasicuzumab. And we are not giving them to this their drug and we are giving we have involvement with some development milestones, but no control over the trial. They are running the trial. And if successful, however, we have an option to purchase the company and then therefore access the therapy for patients with AMR. Finally, and we're very excited of course about AAGES 2, our Phase 3 trial for CSL-one hundred and twelve, our APO A1 product that increases cholesterol efflux.
I've talked to you a bit about this before, this theory that early on in the lifespan of somebody who's had an acute myocardial infarction, they are at the highest risk for a repeat event for the 1st 90 days or so. And this therapy is intended to increase efflux during that period and therefore reduce that risk. And that's the experiment we're conducting right now. The study is going very well. We've have active enrollment in over 45 countries.
And we've just had PMDA approval for Japan to join the trial. And Japan is a very sophisticated cardiovascular market that both scientifically and commercially support such innovation. In addition, though, of course, we have activated over 900 sites. And I just told you that in the bone marrow transplant study, they have 25 sites. And here we have over 900 sites already activated and we're heading towards 1,000 total sites.
And we've recruited over 7,000 patients have been randomized, which is exactly on target for where we thought we'd be right now. Throughout the study, as is typical for these large and long outcome studies, we have an independent data monitoring committee. And they continue to look at the safety of the study and make sure that it's safe to continue. In addition, however, as is typical of these type of trials, we put in some futility analyses and the IDMC also conducts that futility analysis and makes a recommendation to myself and others as to continuation or not of the trial. That first futility analysis will occur somewhere in 2020.
It's not something normally we broadcast, but we will be able to give an update after the end of the year results and where we are with that. So stay tuned, but we're very excited and it's doing quite well. So I know we're running short on time. I just wanted to make a few summary comments. So here is our new baseline.
This is our portfolio as of this month, December 2019. A balanced portfolio showing activity in all 6 therapeutic areas, in all phases of development and with partners as well. It shows, as I said before, at times multiple approaches for disease and that is intentional. And so we are very excited to bring these important medicines forward to patients who need them. Expected progress in the next 12 months, again, this is progression from one phase to another.
We'll make progress in CSL-1 minute 2 and other programs throughout the year, but they won't progress to a new phase. So progress will include you heard from Andrew about the haptoglobin and subarachnoid hemorrhage going into development. We also have 2 other complement inhibitors that will be going into active development as well. And we are very excited about them. In Phase 1, Diana mentioned the CSL-three sixty two for SLE.
And of course, we also, as I mentioned before, are anticipating bringing forward CSL-seven eighty seven as well. Again, all of these programs require at some time they require health authority interaction. And so some of our start depends on those interactions as well. In Phase 2, we're very excited to get the anti VEGF B program started. And of course, we have the adjuvant quadrivalent cell vaccine, say that a few times, going into development.
But as Russell said, that really could be a landmark program. And in Phase III, we are hopeful to take forward Hey Garda in Japan and garidasumab globally. Now again, we don't take Phase III starts lightly. We do a lot of analysis internally. We meet with regulators to make sure that the program we want to run is doable.
But that is our plan and we'll keep you up to date on that as well. And of course, then we'll have some post registration activities as things that we are bringing forward now and registering will actually launch. So second to last slide, the significant target launch dates, of course, 2019, I talked to you about the beginning, 2020. We have our PID label expansion in Japan, our Idelvion 21 day dosing. We didn't talk a lot about that today, but that is an exciting feature of Idelvion and our FLUAD quadrivalent for 65 years and older in U.
S. And Europe. And of course, through the 2021 to 2025 period, we have a number of different products, lifesaving medicines coming forward in that time period to add quality to patients' lives and improve the outlook of their lives and add value to CSL. So I don't have a lot of time, but I just wanted to finish on our therapeutic areas, our 6 therapeutic areas, and the progress we've made in the highlights of 2019. And I'll just recap very quickly.
1st, in immunology and neurology, of course, we've had some great success with Hizentra and we're starting new trials with Hizentra. And of course, the garidasumab data has us very excited internally and we can't wait till we can actually share the full data set. In HNT, we've started 2 very different programs, but for a very difficult disease and a very important disease, sickle cell. And 1, of course, is a plasma product, but one is our new cell and gene therapy, which then embarks us on a new strategic platform. In respiratory beyond Ximera, we now have first patient in for CSL-three eleven that you heard about today.
In cardiovascular, of course, CSL-one hundred and twelve, the AAGES 2 trial continues on doing very well. But now, of course, we've added to that portfolio with CSL-three forty six. In transplant, our programs are going very well and we will now have 2 approaches going in graft versus host and 2 approaches going in AMR at the same time and they will progress along this year. And lastly, of course, in influenza, we have a FLORIA Quadrivalent Flu Cell Vax and of course, the adjuvant quadrivalent cell vaccine that's getting started in development. So with that, I want to thank you for your attention.
Invite my colleagues up to the stage. We'll have a final Q and A session and encourage you, of course, to give us feedback and give Mark feedback as we come to the next round. So again, as we're getting ready Sorry, operator, go ahead.
Okay. So over there.
Dave Stanton again from Jefferies. Just want to circle back on 112 and what you said about the release of the futility analysis. Just want to reiterate, you're saying you don't usually broadcast the results of futility analysis, but you will update the
we pass through that. But it's not a usual press release type of thing you talk about.
But you will be issuing a press release?
No, we will not. We'll just let the market know in due course with our end of the year results.
So it will be part of the F 'twenty result we can expect to
Correct. Okay.
Very good. And then in terms of perhaps for Bill Campbell, if you could talk about the growth in off label use of Kcentry. You've talked about, I guess, warfarin use. But what are you seeing in terms of use in bleeding, diathesis inside hospitals and the like? Thank you.
Thanks for the question. And I always feel compelled to begin this answer with, it is off label. Our label is warfarin reversal and that's what we control and where we promote exclusively. Having said that, there is organic use outside of that labeled indication. If you look in the U.
S. At the overall volume of Kcentra, use outside of warfarin reversal is on the order of about 60% of total use. Some of that is in the oral anticoagulant reversal and some outside of that space. Both of those areas have continued to grow as it has within the Warfarin Reversal segment.
It's Andrew Grutsall with MSC Marquis. A question for Russell, just in terms of, I guess, next generation research into flu vaccines. Just your thoughts on some of the universal flu efforts and anything you might be doing around that as well.
Yes. My opinion hasn't changed from what I've said before about Universal. And I think the position of the flu academic sort of space, it's a long term challenge. We're contributing to a collaboration, an academic collaboration that's really trying to understand the immune response to vaccines and flu to figure out whether there's a place we're missing that we could attack with regard to trying to target immunization that's better than we have at the moment. There are a bunch of biotechs out there trying their hardest to do something.
I don't think there any that anybody's got a particularly strong answer right now to addressing that challenge. So we continue to collaborate, but it's not a central pillar of our research efforts.
Okay. And just a follow-up question on pandemic. I guess just any color you can give us on sort of where you're at in the U. S? I guess there's been a focus by BARDA on pandemic and then anything in Europe or other areas that we should be focused on.
Look, we have relationships, obviously, in the sites of manufacture with U. S, in around Holly Springs, with the Australian government around Parkville. And around Liverpool, we have a relationship with the U. K, but we actually have some agreements with other It hasn't really changed. The cell culture product out of the U.
S. Site really will is really sort of demanded fully by the U. S. Government. We don't really have a lot of options for commercializing that outside of that environment.
In the middle of the room?
David Lowe from JPMorgan. Russell, back to you again. Just the I mean, we say the quadrivalent fluid is coming. Just wondering how you think about that versus the competitor there with the high dose. Does this differentiate in a meaningful way?
Look, they're very different, as you're alluding to. Our vaccine, we generate the data that we have that encourages ourselves and the health authorities and vaccine experts to keep using it. I think there's space for more than one vaccine. If you think about the volumes that are required to supply the market, we actually need more than one vaccine because no manufacturer can supply for by themselves in any of these spaces.
And one for you, Bill, just on the coming back to Hey Garda and the number one prescribed therapy. I mean, we've seen very strong growth in Takeda's tax zero numbers in recent quarters. Just wondering maybe if you could give us an update on how the market progressed over the period, particularly given CSL's supply constraints?
Yes. So it's really been quite dynamic. I think there's a couple of things that we've seen. You saw, 1st of all, in one of slides, the growing number of patients being treated with a prophylaxis regimen. That started a year ago and or 2 years ago and continued last year.
And TEGSIRO has done quite well, but have largely cannibalized their own franchise within the space. And so, I suspect that was partly by design and I think that's partly owing to the fact that there is quite great satisfaction with Hay Garden in the 2nd year of use as well. So it's really quite dynamic. We finished our 1st year 2017 2018 with a bit over a right around a 50% market share, maybe just over. The marketplace continued to grow last year.
We expanded our number of patients on Hey Garda slightly. Our share has declined, but the size of the pool has opened, as you can imagine. So we remain still number 1. TechZyro has done well and are not far behind us, but largely that's come from SynRise as you would expect.
It's Leanne Harrison here from Bank of America. Bill, you mentioned for Idelvion market expansion. Can you talk about what the timetable might be for some of the major markets, in particular France and any sort of hurdles you might be facing there?
Yes. Sorry, I missed the first part. Was it related to Idelvion?
Idelvion, yes.
Thank you. And market expansion?
Yes. So we have a number of markets that are important to us, France being one of them, Canada being one of them, Spain being one of them. All really important markets. We have approval in those markets and continue to negotiate what we believe would be a fair and reasonable reimbursement for the product. So we think Idelvion is quite special.
We don't think that the value of that should be equal to other factor IX products in the marketplace. And we continue to negotiate. And that negotiation is ongoing and will continue until we can reach a place that we think is fair and equitable for us as well as patients in those markets.
And I've got a question for Russell. You mentioned premium pricing for innovation for Siqueres. Can you give us some indication on particularly flu cell vax and flu add for this season in terms of what sort of price increments you received or you were able to negotiate?
Look, I can't comment on R and D guide. It's a commercial question. I can give a general principle that we do see a premium for those products in the U. S, and the reimbursement in Australia is more favorable with the 4 strain than it has been in the past for the 3 strain. It's very market dependent.
We keep on talking to the providers, the reimbursement people in the U. S. About how well we can price the our products related to the benefits we show. So there is a modest premium for the Selvax in the market.
Noli? Chris Cooper, Goldman Sachs. One for Russell. Could you just remind us what the approximate production mix was, cell based versus egg based for the U. S.
Northern Hemisphere season this year in 'nineteen, 'twenty?
The majority of our vaccine is Flucelvax. It's in the 20s high 20s, and I think Afluria is much less than that, probably onetwo or onethree of that.
And as it stands, do you have approval regulatory wise to step up CellBase should you need to?
We don't need a regulatory approval. It's just about our strategy of how we can enhance our manufacturing capacity.
Got it. And just one for Bill Campbell, please. You mentioned the orphan exclusivity your approach and how you go to market with Kcentra?
Yes, I think we've been planning for this for quite some time. I think we have this beautiful first mover advantage and 7 years we think will serve us quite well. I suspect there could be a bit of headwind with respect to pricing and we'll have to adapt to that as we proceed.
Steve Wien from Evans and Partners. Russell, about I think it was 2 seasons ago in the Northern Hemisphere, flu cell vac showed some superior efficacy to the egg based vaccines. I wonder if you've got any updated data on that, specifically on flucelvax for the latest one?
So I guess that I was trying to emphasize that the data we presented a couple of seasons ago pretty much confirmed, and we've written that up into a manuscript that's now being reviewed at in a journal. And that was a 36% reduction in outpatient symptoms indicative of flu. That's what we presented. There's no update. That's what we have.
But it's complemented by other groups doing observational studies and the sorts of data I showed you in the slides.
And then secondly, you've always stressed the importance of being first to market with any new season. With Sanofi being out for about 3 months, what sort of potential does that provide you in terms of your ability to take some share?
Look, I think the market is evenly balanced. So I think we're in play at the moment. I think the major impact it will have for us is it will help reduce the amount of returns we get rather than taking share because the distribution in the market is pretty well set by midyear. And so it will we'll have we anticipate we'll have fewer returns if that plays itself out in the market.
Okay. I'll take this question in the middle of the room and then check online. Go ahead.
It's David from Macquarie. Just one for maybe Andrew, actually. Gene therapy and hemophilia, some aggressive time lines for launch. I'm just interested in your views on potential uptake and any general observations from the results you've seen to date.
So you're right. So there's been some quite a lot of publications in hemophilia A and hemophilia B space. The with hemophilia B, the dose response relationship seems a little bit more consistent and controlled. So those products will come through. The uptake is difficult to predict.
With the arrival of molecules like Idelvin in the hemophilia B space. It's really raised the bar in terms of what you need to deliver for gene therapy. So I have no doubt there's a place in the market for those gene therapies, but they will struggle against quality products. And they still, of course, with AAV based delivery for both hem A and hem B, face the issue of you've got one shot at the therapy before you develop immunity and do you want to go with the first product to market? Or do you want to wait for an optimized product?
So it'll be interesting to see how that plays out. It's a little hard to predict at the moment.
Okay. Let me just check online if there's any questions.
Thank you. We don't have any questions from any of the phone participants.
Okay. Thank you, sir.
Thank you. It's Saul from UBS. Maybe for Bill Campbell. Bill, that slide you showed the number of patients on prophylaxis in HAE. Do you expect that patient to grow on a go forward basis?
What's the do you have an estimate of the total number of diagnosed and treated patients in the U. S?
Yes. So I think last year I hit this a little bit, but as a refresher, I think there's broadly, if we think about a pyramid, we would start with around 6,000 patients we see in the U. S. Many of those are not treated. And so as you come down the pyramid, we're seeing around 1800 now treated with a prophylaxis regimen using a biologic.
I think that will continue to grow a bit, but the delta between that number and patients that are still using other products, verazir or baronert, I think is relatively small. So I think we'll see some ongoing growth, but I don't think we'll see growth anywhere near what we've seen in the last 24 months.
Thanks. Just one more on gene therapy in general. So we're seeing emergence of some gene therapy programs in other diseases, HAE for 1, and I think also alpha-one in terms of CRISPR or zinc finger therapies. Just Andrew, your thoughts or any of the panelists' thoughts on gene therapy across some of the other plasma products that are in the CSL portfolio?
Look, I would make the same comment in respect of those with the hem b, they're mainly AAV type approaches. You do need very high levels of those molecules, and it will be interesting to see whether they can reach the effective levels. The CRISPR approach for C1 at the moment relates mainly to what's called a disease mutation, and that's a small portion of that population of patients. So we'll just have to keep an eye on it.
And I think in AAT, it's a the phenotypic expression of the disease is so diverse, it becomes even more of a challenge. So we're running out of time. So the last question here in the front. Yes.
Rosemary Cummins from MST. Just looking at the renal transplant, can you give us some sort of idea of how we should be looking at how or what patients will have prophylactic treatment? Would that would you expect that to go across all patients undergoing
In the GVHD space? Well, of course, it's first of all, it's not autologous, right? This is only allogeneic, so you have to split it and it's about twothree, onethree right now. Initial step, let's assume it works. Then yes, if we get a meaningful reduction, I would expect that that be a regimen that would be part of the standard treatment regimen.
Now as we go on, we'll continue to phenotype patients and say, do certain patients benefit more than others, that's part of ongoing science. So it may narrow over time, but I would guess in the first instance, it would be a broader use.
Okay. And then with the treatment side, again, would it be added into the current regimen? Or is there something within the trial that will help you indicate what percentage of the patients would be treated?
So there are no approved treatments right now for GVHD, right? So people are using all sorts of treatment cocktails. And I would imagine it would be added on. I mean, one of the benefits of AAT is it does not create an immunosuppression in itself. And so it would give people the liberty to use some of their other favorite therapies because the combination immunosuppression would not be expected to be more grave.
And that's one of the benefits.
And then in terms of the actual trials, when you have an NC, obviously, there's quite a rigorous process to go through Phase I, Phase II, Phase III. Given that they both have been on the market for some time and are well known to everyone in terms of regulatory, do you have to go through the same sort of Phase II trial? Have you done gone through a Phase II trial before?
So one of the reasons we have enjoyed the or thought this transplant was a strategic place is because you could get a head start. You didn't have to go back and demonstrate the safety of the product, right? And so Phase 1 is largely about safety. Phase 2 depends on whether you think you have to determine the dose or not. And so you saw with GvHD, we're now doing an adaptive design Phase twothree because we want to more characterize the optimal dose for that prevention trial.
For other trials like the trials like the AMR, we feel like we're going with the C1 inhibitor dose we have and we can go right into Phase III. And so it's that part is individualized. Okay. Thank you. Okay.
Well, thank you very much for the excellent questions and the attention. We really appreciate it. Again, we're happy to get your feedback and continue to adapt this presentation to your needs. So with that, I'll say thank you to the panelists. Thank you to the audience.
Mark, thank you, and we're done.