Ladies and gentlemen, welcome to the Sobi presentation of the Q4 and full- year 2019 results. Throughout the call, all participants will be in listen-only mode, and afterwards, there will be a question-and-answer session. I will now hand over to Guido Oelkers, CEO. Please go ahead.
Yeah. Good morning, everybody. It's really my pleasure to welcome you to our webcast on the Q4 results. I think with this, we go straight into the beef, forward-looking statement as per usual. Today, I'm accompanied by our CFO, Henrik Stenqvist, and our Head of R&D, Milan Zdravkovic. 2019 has been a significant journey for the company. Before I get into the numbers, I think it's time just to quickly reflect what actually happened. We really grew now our hemophilia business with the acquisition of Doptelet or broadened it into a hematology franchise. We got our first launch experience with Gamifant during the year, and the $56 million, I think, made our first mark. We had Synagis in the first year under our ownership. As you have seen, the product has performed extremely well. We strengthened substantially our North American franchise.
Not very long ago, our North American franchise was contributing around 12% to the top line. Last year, it contributed 37%. We have invested substantially in our portfolio with BIVV001, and emapalumab or avatrombopag, b asically, we have diversified the company into really in hematology, immunology company with the help of the investments. Coming to the next page. 2019 is indeed the year of transformation as I pointed out, but it is a year of very strong growth. 56% growth on the top line, 72% at the bottom. Organic growth has been very strong, even though we have some parts in our range like the manufacturing business or the royalty streams that are not growing as fast. Overall, the product business has performed extremely well. Elocta 34%, Alprolix 46%. I come back later on how we see this business moving.
The good news is that we still see very strong patient growth, and that gives us a lot of confidence moving into the future. In the immunology sector, we have, let's say, very strong track record now with Synagis. We'll explain a little bit later on how to view this business. The Gamifant launch, I think, at least measured up to my expectation even though there was a couple of bumps on the way. $56 million with restricted indication, I think is a very respectable result. In addition, with these two acquisitions now, we really built our pipeline, but also we executed, I mean, obviously two important deals and established us as a credible player in the M&A space.
We have recently set up a company in China, and this will be another growth platform for us moving into the future, in particular for Gamifant, but also for other products in our range. We are restructuring, obviously, our specialty care and partnering product portfolio. This business used to be in 2015, 60% of our business. Now, over time, it's becoming increasingly irrelevant given its less profitable bias. We really focus on the core. Basically, when you look at the next slide, how we have performed at constant currency, 48% year to date or last year versus 2018. Here you can see how this business has transformed over time and how we have now really established two very strong franchises that will be the engine for the company moving forward.
We have not only moved the existing business or the on-market business, but also our pipeline as you can see on the next slide. What is important to note is that with avatrombopag, we have three indications. In the U.S., we have today only launched CLD and ITP. Moving forward to become the first TPO- RA registered in CIT, and we expect the phase III results in Q3. This gives us a significant platform when you think about internationalizing this franchise. We have BIVV001 in our stable, and Milan will talk more about this. BIVV002 in the preclinical phase for hemophilia B. With emapalumab, we have a bundle of indication expansions, and we still have some ambitions also for anakinra.
As you know, we are participating, what we termed in the past as MEDI8897 and ILSA, emapalumab as well, and we have an option on two oncology assets, one in phase I and one in preclinical as part of the [fluing] transaction. It's a nice portfolio that should basically bring us into a position of dynamic growth over the next couple of years. Next slide. Basically, when you synthesize this, we have a very clear strategic ambition. We want to maintain the hemophilia leadership. We think that we have the best EHLs in our stable, and we can sense that factor business is here to stay, and we have the future with BIVV001. We have opted in, as you know, last year. This was now helping us obviously to position ourself as an important player in hemophilia.
We are diversifying and building Doptelet to scale with this establishing the hematology franchise. We are extending Gamifant into secondary HLH, but also into acute graft failure, and Milan will talk about this later. Expanding Kineret and growing Synagis, and we allude to this how we think about it. When we now turn to hematology, here you can see the growth. As you know, already alluded to, we have very strong underlying growth, and we don't see that this trend is discontinuing anytime soon. Turning to Elocta. It's very nice to see that we gained speed again in Q4, and this is not only reflected by sales but also by patient growth. The growth is really driven by EU5 markets and the Middle East.
The product is now well-established, but we are still having opportunities to penetrate, and one should not forget that there's a very substantial share still out there to get for us and to convert in the short-acting sector. Very nice for us was that we got just recently in January, the approval in Russia, which is an important milestone for the franchise. These are some soundbites that we have picked up at EAHAD, a conference that took place last week. I think it's important. For us, these are some important learnings. These are original quotes from leading KOLs in the sector. This is not just one KOL who told us this, but many KOLs share this view now that factor replacement remains standard of care.
Even in the inhibitor sector, eradication of the inhibitors is a key objective, and they see ITI treatment still as a treatment of choice. Risk-benefit ratio depends on the significance on the unmet medical needs. I think there's a growing understanding in the community that with new therapies, you have trade-off decisions. I think there is a bit of a, at least in Europe, and this is also documented by the uptake data, you can sense there's a bit of more skepticism now in the community, whether this risk-benefit ratio is actually that favorable or in other words, whether convenience will actually top safety concerns. We are convinced that we have the best-in-class hemophilia treatments in our portfolio, and therefore we are confident with regard to our future. Quick snapshot into Doptelet.
Here, we wanted to just give you a little bit of a frame on how we think about it, because we think that Doptelet is a little bit underrated as a product right now. The main indications are obviously ITP. This is a $2 billion global market. As you know, we have global rights. The CIT market, based on our estimation, will clearly exceed $1 billion. There are estimates out that suggest it could be even close to, and CLD is around $300 million alone in the U.S. We think that Doptelet is a differentiated product, and we believe that the window of food intake that you have to consider with the leading competitor is not trivial, and we believe that once-a-day dosing is very positive for this product, oral administration, and also that you don't have to worry about hepatotoxicity.
We believe Doptelet is getting into a structured market, very sizable, with a strong underlying growth, and we come in with a differentiated product. Hence, we are very bullish about this product. Now turning to immunology. Obviously, when you come to this chart, this chart is pretty much skewed by the seasonal effect now of Synagis. But it's nice to come out on the high, and I think I've commented already. For me, important to note is that Kineret, at constant currency, is growing at 12%, and we don't see that this trend is diminishing anytime soon. Now coming to Synagis, I think we are performing very well. We have performed very well in Q4. With the overall increased demand and referrals, it really drove this. We have a mid-single-digit underlying growth, and we have obviously benefited to a certain degree from the RSV season.
Let's say there is also an effect from the wholesaler side, and I think we guided on this at this year, or last year, end of last year, we sold in probably around $6 million more than AstraZeneca has done at the same point of time the year before. I think to evaluate this product, which is a seasonal product, you really need to look at season by season. We guided you that when we took the product, it was a product of around $269 million for the season. We think that when we completed this season in the 2019, 2020 season, we will have sold between $290 million-$230 million, which means mid-single-digit growth versus the 2018, 2019 season. We are very happy and basically see a validation of our thesis that this product will perform well under our ownership.
This product is 20 years on the market, so we are quite gratified that we can drive continuous growth. Gamifant, we have talked about. This product is still at an early stage. The consumption obviously is driven by the weightage, duration of treatment, and let's say the average dose of the patients. It's early days. We are excited about the fact that the natural definition, essentially the North American Histiocyte Society is broadening the approach and has broadened the understanding of primary HLH. This will help us in the years to come, and we see strong underlying demand for the product. Yes, it's not yet a linear extrapolation of the product that is possible, but overall, the magnitude, I think, of how we established the product last year was a positive event for us. Now I would like to ask Milan to talk about the pipeline.
Thank you. Thank you very much, Guido. As mentioned in the past couple of years, we have made a very deliberate effort to strengthen our innovation pipeline within our areas of strength, being within hematology and immunology, and this is illustrated on this slide. We now have two ongoing phase III studies, one for BIVV001 in collaboration with Sanofi, and one for avatrombopag in chemotherapy-induced thrombocytopenia. We have our phase II-III study with emapalumab in adults in non-primary HLH, which is now open for enrollment. In addition, we have the ongoing phase II study with emapalumab in MAS. In the registration phase in Europe, we have the primary HLH indication with emapalumab, the familial Mediterranean fever indication with anakinra, and we have just very recently submitted a chronic immune thrombocytopenia application with avatrombopag.
As mentioned, we have an option to an immune oncology asset in phase I and financial rights to a potential follow-on molecule within RSV. On the next slide, I will share more details on pipeline events in the coming period. We expect to initiate the pediatric phase III study with BIVV001 by year-end. Obtain phase III readout on chemotherapy-induced thrombocytopenia with avatrombopag in second half of 2020. Submission of DIRA or deficiency of the interleukin-1 receptor antagonist in the U.S. in mid-2020 with anakinra. Expected approval emapalumab in EU mid-2020. Complete enrollment of 10 patients in MAS with emapalumab and subsequent meeting with the FDA by year-end. To initiate the phase II study with emapalumab in preemptive graft failure by year-end. If can I have the next slide, please?
On this slide, I'm showing the design of the ongoing phase III trial with BIVV001 in previously treated patients with hemophilia A above 12 years of age. The study will enroll 150 patients and include the annualized bleeding rate as primary endpoint. Also include additional measures such as ultrasound and activity monitoring, to better document the unique profile and ability to normalize the life of patients with hemophilia A with BIVV001. With that, I hand over to Henrik to discuss the financials.
Thank you, Milan. Good morning, everyone. Let's start with a financial summary of the quarter. Revenues for Q4, as we saw, amounted to SEK 4,890 million, corresponding to an increase of 90%, and 82% if we look at constant currencies. Elocta and Alprolix both saw strong double-digit growth, showing continued momentum. In both products, we are seeing this growth across Europe and the Middle East. Synagis sales of SEK 1,656 million were above our expectations. We see positive signals as a result of improved commercial effectiveness, but sales were also impacted by wholesaler stocking, positive growth to net impact as well as the severe RSV season. It's important, as Guido said, that we evaluate Synagis in season, and that is really measuring July to June as there can be monthly variations. For this season, 2019-2020, we expect sales of between $ 290 million-$300 million.
Gamifant sales of SEK 180 million showed a rebound from the SEK 67 million that we saw in Q3. As discussed, that we expect some continued volatility in the quarters to come due to the nature of the disease and the small patient population. The underlying trend is very positive. In terms of organic growth, that is adjusting for the acquired growth from synergies and also Doptelet, we saw year-on-year growth of 20% in the quarter at constant currencies. In Q3, we discussed our slightly lower gross margin due to the seasonal product mix effect, were primarily driven by synergies and the then lower Gamifant sales. As expected, we saw a quarter-on-quarter increase leading to 78% gross margin for the quarter, with a full- year gross margin of 77%, which is then up from 74% a year ago.
Adjusted EBITDA reached SEK 2.38 billion for the quarter, an increase of 160%, this corresponded to a margin of 49%. Again, the margin of the quarter was obviously impacted by the seasonality of all the synergies. Adjusted EPS, that is adjusted for non-recurring items, for the quarter was up as much as 122%, also the full year Adjusted EPS showed very strong growth of 33%. The operating cash flow of SEK 976 million for the quarter and SEK 3.6 billion year to date signals continued very strong operating cash flow. The net debt as a result of the Dova acquisition increased from SEK 7.6 billion in Q3 to SEK 15.4 billion at the end of Q4. This increase is obviously driven by the roughly SEK 8 billion acquisition of Dova; it was also impacted by the $50 million payment to Sanofi related to the early opt-in for BIVV001.
Also, the positive impact from our underlying business performance. If we go to next slide. I also want to discuss our revenue and OpEx development over the last two years. The fact that we've diversified now into new areas has and will have a significant impact throughout our financials. The top blue chart illustrates revenue, where we have 90% growth for the quarter and 56% for the year. As we can see, approximately 38% of our Q4 revenue related to the new products, particularly Synagis, but also Gamifant, and to a smaller extent, Doptelet. Let's next discuss OpEx, where we have a trended view, in the bottom gray chart. There are a few key points to be made here. First, the OpEx in our base business is relatively stable, where we have increased investments primarily in hemophilia.
Secondly, as we can see, we have invested and we will continue to invest in synergy's Gamifant and Doptelet in order to drive the long-term growth and profitability. Both in the commercial and the R&D areas, and also in the internationalization of Gamifant and Doptelet outside of the U.S. You can see this trend in Q4 2019, where 36% of our SEK 1.4 billion OpEx relates to these new products. Just as a reminder, even though the synergy's revenue is seasonal, the expenses are more evenly spread throughout the year. Finally, a major driver of the Q3 to Q4 OpEx increase was due to the impact of Dova, corresponding to about SEK 150 million in Q4. Lets see the next slide. Let's turn to the development of operating cash flow per quarter and our cash conversion over EBITDA on the latest 12-month basis.
We see a continued very strong cash conversion between 60% and 70% of EBITDA over the last three quarters. The net debt of SEK 15.4 billion at the end of the quarter was a bit lower than planned due to the strong operational performance. This level corresponds to a pro forma leverage of well below 3x . This level is expected to decline to 2x-2.5x EBITDA during this year. Thank you, and back to you, Guido.
Yes. Thank you, Henrik. What I would like to share with you now is really how to think about us now moving forward. Henrik has alluded to the fact that there's a lot of investment or spend going into Doptelet and Gamifant, our future growth drivers. It feels a little bit like the soccer player who has to kick the penalty. He should not waver and think about twice whether he should choose the penalty, and we don't need to waver or shouldn't waver now to invest into these significant growth opportunities moving into the future. We have now products in our hands, and that's the reason why we upgraded also the guidance, just to clarify what we see now, that there are more than $500 million sales related to these two entities, but they need to be developed.
They need to be developed commercially, but they need to be also developed from an R&D standpoint and from a medical standpoint. These costs of developing the products are reflected, obviously, also in our guidance. We just wanted to make sure that this is absolutely clarified. We feel when you think about the opportunities now moving forward, and you have in mind that we think that we can grow our two main franchises with the help of these two growth drivers at double-digit growth midterm, and midterm, we mean three years, then I think this is worth all the effort. We also wanted to clarify that our non-core specialty care business, as we have alluded to earlier, we will have an expected negative impact on revenues of around SEK 3 million-SEK 400 million.
This is just related to the fact that we have discontinued some relationships with some of the partners and essentially focusing now on our core business, which is much more profitable and where we also see the long-term growth. Coming back to the financial outlook. When you look at our financial outlook of SEK 15 billion-SEK 16 billion on the top line, primarily driven by hematology and immunology growing double-digit, and also in the years to come, I think this is how you have to look at us. This is including, obviously, the reduction on the specialty care business. Our EBITDA reflects the fact that we believe in the future, particularly of Doptelet and of Gamifant, and we called out the negative effect of Doptelet, meaning gross margin minusing of the expenses for R&D and commercial expansion. This delta is around SEK 500 million.
We are confident looking into the future, and I'm very bullish what we can do as a company. I'm very excited that we have now broadened the franchise into two areas and that we have the hands in our hand. With this note, I think we are now up for question- and- answers.
Thank you. Ladies and gentlemen, if you have a question for the speakers, please press zero one on your telephone keypad. The first question comes from the line of Eun Yang from Jefferies. Please go ahead.
Thank you. Just so you know, if I missed it, I apologize. When you mention double-digit growth in hematology as well as immunology in the midterm, next to three years, particularly in the hematology franchise, does that imply you expect a double-digit growth in hemophilia, or do you think that double-digit growth is largely coming from Doptelet?
Yeah. As you know, we don't typically guide by product. What we wanted to make sure is that we are convinced that we have great products in our portfolio. 34% growth with Elocta last year feels good. Yeah? We feel good about the continuous expansion of patients. Now, there is obviously uncertainty with regard to the new entrants. We have seen the uptake data in Europe, also now particularly for Hemlibra, which are not so convincing and compelling as they are in the United States. It's early days. What we wanted to say is we stand by our products. We think that we can continuously drive them. What we want to now steer the discussion towards to is that we say, let's think about this broader.
Let's think about Sobi broader and as a company that can drive its core business double digit. Then you can have different views on how strong we grow our hemophilia franchise. Again, we are convinced that we have the best products in our stable and that this remains mainstream. Basically, we overlay this with Doptelet and those franchises together where we are convinced that we can make a significant impact with this product, with a differentiated product in a very well-structured market. We have demonstrated that we can compete in those environments also with big pharma, as shown with the hemophilia franchise, that we can have an impact. Yeah. We don't provide guidance by product, but we wanted to make sure that you are left with a view, actually, core business of Sobi grows double digit.
Thank you. Question on Gamifant?
You're welcome.
Can you give us Previously, you said the EU approval is expected middle this year. Can you give us an update on Gamifant EU approval timeline? Lastly, on Doptelet. ITP is an established market, so you need to capture market share, but CIT is a market that you would need to cultivate. When you think about uptake of Doptelet in these two indications, how do you see uptake would look like? Which one would be easier to penetrate versus more challenging? Thank you.
Thank you, Eun. Let's start with Gamifant in Europe. We are currently in the discussions with EMA, and we have, at this stage, no new guidance. We have outlined, we have guided earlier, and we are just now waiting for some responses from their side. We have no new update at this stage either way. With regard to Doptelet, it's true. We are entering. We have the product registered today in CLD in Europe, and we're expecting in Q3 the approval for ITP in Europe. Basically, end of Q3, beginning of Q4. Just to give us a little bit of flex. There's a bit of luck it's in Q3. Basically, we think this is obviously a significant opportunity because also in Europe, this is a very structured market.
We will have to compete now, maybe to your question, how do we think about the competition? I just use, for argument's sake, the U.S. market. It's a give and take, it's a billion-dollar market which is dominated by Promacta and with a significant position by Nplate. You have Novartis and Amgen as our competitors, we come in with a product that is oral once a day, no hepatotoxicity, and you don't have to worry about the food intake. Sometimes we believe this is a little bit misunderstood or not properly given justice because if you have to take a product, if you cannot eat two hours prior to intake and two hours after, or you have to align your life. When you think about an average duration of treatment of nine months, that means you need to juggle this.
This came out of some insight analysis loud and clear that there is a demand for a new product. This will take some time. We think that this is a compounding business where we then gradually take share and towards the end of the year, we will take a significant share of the total market. In terms of absolute sales, I think it will take probably two or three years that this market share is very substantial. In addition, you have the readout of the phase III in CIT in the third quarter. Here we will be the first to market. We think when you look at the structure of this environment, minimum, I think it's a SEK 1 billion opportunity market, possibly more.
Let's say, and we now come into this market and the question for us is going to be how we will approach this market. We know that actually similar to ITP, the hematologist plays an important role for ITP anyway, but even for CLD, the existing indication as a decision maker as well for CIT. There is some leverage with the team that we have in place, but we may have to complement the team, and this is something that we are currently thinking of. We think that we will have a very good shot. It's not going to be a walk in the park and competition will invite us to take their share, but we have a strong proposition. I hope that this gives you a little bit of a flavor.
Thank you.
You're welcome.
The next question comes from the line of Emmanuel Papadakis from Barclays. Please go ahead.
Emmanuel Papadakis from Barclays. Thank you for taking the question. Maybe just a couple. Hemophilia. I wonder if you could give us any color on the geographic European split of sales for both Elocta and Alprolix. From some data we've seen, it seems relatively concentrated, for example, in France, but perhaps you can tell us if that's wrong. If so, sustainability of that concentration would be also interesting to hear your perspectives. Maybe a follow-up on Doptelet. You obviously had the ITP approval in the U.S. a while ago. It still seems to be relatively slow progress there. Any comments on when you would expect that? Is that a gradual change, or should we be looking for a step change at some point? Where you're going to be spending that additional SEK 500 billion over the coming year, is that just sales reps?
Would be helpful to know. Final one on Synagis. You talked about mid-single-digit growth rate for this year. Do you think that is sustainable over the next couple of seasons? Are you anticipating any major changes in the AAP COD guidelines? Thank you very much.
Thank you. Yeah, no, maybe we start with hemophilia. It's true that we have a high market share in France. We are having also very high market shares in Switzerland and Ireland. We are getting significance also now in markets like Germany, Italy, Northern Europe. You see Spain, you see really a significant ramp-up of our presence. Whilst maybe historically it was more skewed towards various markets, I don't think that this is now holding forward-looking. We have very nice growth opportunities now in Central Eastern Europe. Obviously, as I mentioned earlier, we just got the approval. We still have to get the price, but we got the registration of Elocta in Russia. Yeah. I don't think that basically we have a concentration risk as such.
Let's say, yes, we have some markets that are larger. We have growth opportunities in others. Obviously, I think we are prepared to defend our position and articulate to the community why Elocta is a very strong choice. Now, with regard to Synagis, is it sustainable? When we did an insight, we basically realized that there is still a lot of leakage in the system of people adhering to therapy, and even babies therapied. We had a significant stronger demand increase last year than what in the end we were able to dispense, that got dispensed, because we were not yet totally synchronized in with the hub system. We think that these opportunities are there also midterm. We don't think that the Synagis in our midterm growth story will come to an end anytime soon. We still have significant opportunities ahead of us.
The AAP guidelines is hard to judge. We are in the hands of others. We will try to make a point. Will our point be strong enough or not, honestly is out of our hands, so I don't want to speculate. I hope in this regard to Doptelet, slow progress is correct. I think you need to also recognize that Dova, before our ownership, got the registration in July last year, was probably, I wouldn't say surprised, but probably not as well prepared as you would think. They were in discussions with us on the exit. That didn't really enhance their preparation for the launch either. Last year, we had the product and now ownership for essentially one and a half months. It's not just good enough to put the hands on your business and then automatically it's going to increase. We see signals.
We brought in new leadership. We have a very rigorous methodology on commercial effectiveness. We have our metrics overlaid there. I was with the team last week. We're trying to create the right excitement. We believe in the product. We believe in the team that we have now in place. We will, I think, during the course of this year, maybe more skewed towards the second half, but we should already see something in Q2. You will see a very steady increase as this is overlaying different layers of patients, essentially on a monthly basis. We should see some response, but let's say more significant in the second half, and it's probably more every month, it's a steady process, and then hopefully we get into a bit of a snowball effect towards the end of the year.
Thanks very much.
You're welcome.
The next question comes from the line of Richard Parkes from Deutsche Bank. Please go ahead.
Hi. Thanks very much for taking my questions. Three, I think. Firstly, on the guidance, it's a wider range than you've given previously. Could you just discuss the swing factors to that, and you're thinking over giving a wider range than in the past? I think historically you've given a conservative guidance range at the beginning of the year and then upgraded through the year. I'm just wondering if this marks a change in that policy. Secondly, related to that guidance, just wondered if you could help us by talking about the visibility that you've got on Elocta for 2020. Sanofi seemed to get taken a little bit by surprise by the competitive impact of Hemlibra in the U.S., I'm wondering what visibility you've got going forward, and whether that's helped by certain tenders, et cetera.
Maybe you could also help us understand in what territories you're now experiencing full impact from Hemlibra competition, where it's fully reimbursed, and how you expect that to evolve over the year. Final question is just clarification on Doptelet in terms of the sales that you've reported. That six-week number implies they're annualizing at about $30 million versus IQVIA volumes in sales, which look to be materially lower than that. Just wondered if you could help us understand whether IQVIA volume data is not very good in this category, or whether the 4Q number was impacted by inventory changes. Thanks very much.
You're welcome. Yeah, maybe we start with the hemophilia part. I think why do we have a wider range? We have a range because we have a couple of areas. First of all, you establish products, essentially new products, and you are in a launch phase. With this, automatically you have a little bit more variability. We have obviously, we face competition in hemophilia, but we have also operated in a generic environment. There are a couple of variabilities where we felt it. As you know, Richard, we are not the guys who are talking a lot and promising a lot and then seem to under-deliver. We rather like to deliver what we are doing, and that's the reason why we provided a range that covers us. We are confident that we can make a significant impact.
With regard to Elocta, yeah, it seems that I think there was a disproportionate impact on Elocta in the U.S. when Hemlibra launched. I'm sure that Sanofi would love to give you there some explanation of how this came along. What our understanding is that basically there's a bias for Hemlibra given that convenience features on the demand pyramid much higher than in the European setting. Obviously in the European setting, you have the connection with the centers, with the physicians, which are much stronger. You have physicians who are probably need to be convinced and who are very interested in safety data as well. Then basically comes also this growing time and I'm sure you're aware of the Mike Makris quotes on even mortality and other issues.
There's now, I think the community is more realizing now, it's also sometimes timing, that new therapies are not a panacea. There's also the growing awareness that it's not like when you are on new therapies, you can forget about factor. You still need factor to complement the therapy. It's a trade-off, and I think we are not saying that new therapies are not going to have a market. We are saying that EHLs will have a market, and we are convinced with our offering, we have the best EHL. We have a couple of things now in preparation. We understand, to be honest, our understanding on what real world shows has grown significantly. We are also understanding how we can enable patients and we are working there on digital solutions and allowing them to liberate their life is under the rule.
We have many other initiatives just to make sure that physicians and patients have an option to have an active life and manage their disease as opposed to believe that they are cured. Yeah. That they are normalized, for argument's sake. I think that works quite well. Now with regard to the, what was the other question? On the sales reported with Doptelet. The Doptelet sales, this is the unfortunate story, is we're not talking about a product that now makes a billion dollar. With this, you have certain sales, as you know, IQVIA is a panel that then extrapolates for the universe. I think that panel right now is not yet indicative for our Doptelet revenues. Hopefully, let's say, with growing business, this panel becomes more representative.
Sorry, just one follow-up. If we take that six- weeks number that you've reported and annualize that, is that a better guide for the underlying sales at present, or was there anything lumpy in there?
I think December was a good month. We are talking really small numbers. Could there be the one or the other 100,000 that basically was advanced from last year? Maybe. We don't see it, and I kind of also, to be honest, I cannot validate this now. I think it will appear in our chart, Doptelet, and you won't need a magnifying glass to find it. It will become a significant product. Let's say that will propel our sales.
Great. Thanks very much.
The six weeks, for whatever it's worth, it's one data point. I think look at our Q1 will be the next, yeah.
Thank you.
The next question comes from the line of Erik Hultgård from Carnegie. Please go ahead.
Yes. Hi. A couple of more questions, if I may. First on Elocta, could you talk a little bit about the performance that you've seen for Elocta in Europe so far in Q1, and in particular, whether you're seeing any impact from Hemlibra in markets where they have secured market access and reimbursement. Secondly, on BIVV001, should we assume regulatory submissions in Europe 2022 similar to the U.S., or should we assume that the EMA will require sequential pediatric data as was the case with Elocta? Finally, could you talk a little bit about the Doptelet phase III study in CIT with data due Q3? How should we see the development risk in this study? Could you talk about the design, what sort of historical data has shown and the power of the study, just to understand the risk of failure in that important trial? Thank you.
Thank you, Erik. Pleasure. Elocta Q1, we cannot comment. I can only tell you that we come from the last year with a lot of confidence into this year. Unfortunately, I can't tell you more. We have obviously a couple of markets where Hemlibra had market access last year. Full access, one of them being Germany, and it hasn't affected our patient acquisition. BIVV001, let's say there basically we think that there is a pediatric study need, but our timeframe is 2023. Milan, you want to comment?
No, I agree. Approval in 2023 is what we have been saying. Yes, there is a requirement in Europe for pediatric data, and we will have to fulfill that.
Yeah. On the development risk, we are obviously confident to get it with CIT, but maybe Milan also hears you.
Yeah. I think there's a number of data points that supports a role of TPO receptor agonist in the space also of chemotherapy-induced thrombocytopenia. The study has been designed taking all these data points into consideration. There has been FDA discussions around the phase III design, including the endpoints. The study is well underway. We have approximately 75% of the patients enrolled. The study is well powered. We are confident around, you can say, the CIT. This was also one of the reasons around the attractiveness around.
All right. Thank you so much.
Thank you, Erik.
The next question comes from the line of Peter Sehested from Handelsbanken. Please go ahead.
Yeah. Peter Sehested. I just have a few housekeeping for Henrik. Could you please help us with a number what we should expect for depreciation cost 2020, also in terms of the absolute level of [audio distortion ] for over the SEK 6.3 billion that you had 2000.
It was a little difficult to hear you, Peter. I understood your question to be about the amortizations for new rights.
I hope you can hear me better now.
Now I can hear you. Yes.
Okay. Sorry. Now I'll just repeat them very quickly. Just some brief guidance on amortization and depreciation costs for 2020, as well as the incremental spend above the SEK 6.3 billion that you had in 2019, which we should expect for 2020.
When it comes to amortization of these new rights, you can expect that we amortize intangibles over 15-20 years. If you go into the note in the report, you see the amounts. When it comes to an absolute OpEx number for 2020, we don't give any further guidance than the one we have given. With a range, obviously, and the impact from Doptelet for the development and launch costs. At this stage, we don't give an absolute number on OpEx.
Okay. Thank you very much. I just have one question on Hemlibra, then, just to sort of understand the dynamics in the U.S. For product in such a disease to climb, as I see it, that can only happen if you have patients switching out of Eloctate and into Hemlibra. Is that also how you understand it? Roche at their call said that the underlying patient dynamics are unchanged in Europe, but it's until now been a question of lack of access in market. Is that also how you see it?
Based on the data points that we have obtained, they suggest that there were switches from Eloctate to Hemlibra. You need really to ask Sanofi about further explanations. Now, yes, Europe, there is always a question of market access. Absolutely. I'm sure that this may or may not have influenced Roche so far. That's basically in every European launch the case. I think, our point was more, yes, there will be, and to be proven, obviously, there will be more market access as they go along. The next six months will already be quite indicative. Yeah. Because what basically is going to be the game. You don't have to wait, maybe for 18 quarters to figure out whether there's an impact or not. You may see this faster. Again, we're not professing here that they won't have an impact. We're just saying that we feel we have a good therapy.
Thank you.
You're welcome.
Additional for Henrik, and I'll jump out. Tax rate for 2020. Is there anything we should think are some of the amortizations that are not tax deductible, et cetera?
Yeah, what we expect for 2020 is slightly lower tax rate than we've seen in 2019.
Thank you.
The next question comes from the line of Johan Unnérus from Pareto. Please go ahead.
Thank you for taking my question. Some follow-ups mainly. Gross margin 78% in 2019. Is that a fair level also for 2020?
Henrik.
If you look at the full year, it was actually 77%.
Oh, yes.
Yeah. That's a fair view also going forward here for 2020.
Yes. On Elocta royalties, obviously your quarterly number is sort of a best guesstimate or proxy for the underlying. Is there any true ups or adjustment that you want to highlight? Perhaps you've done that in the beginning of the call, anyway, is there anything to point out there?
No, not really. Not really for this quarter.
Good. On Synagis, I remember from the acquisition, I think you were talking about slight growth, sort of 2% or thereabout, out from memory. Now you're pretty clear about mid-single digits. That's a more positive take. Given the strong ending in 2019, is that also something we should have in mind for next year? Of course, there will be seasonal variations excluding that. Clearly a couple of years out, three years out, if that's what we should look at for the midterm, mid-single digits is clearly higher than 2%, anyway.
Yeah. No, it's higher than two. Yeah. Let's say, at this stage, we haven't given out the guidance for Synagis midterm. On the immunology franchise, as we alluded to earlier during the call, we have a lot of opportunities still to grow the product, and therefore, we are going after these opportunities, and we think that this is not just another year. We're not giving guidance for the product.
Thank you. The message you get from Sobi, and the impression is clearly that you're more focused on your core business, on your two main divisions, and you're talking about both mid-term double-digit growth, and that seems to be the case also for this year. I think that's very good to have that sort of clarification. Should we expect you to continue to guide for the annual outlook on these two core businesses going forward?
Yeah. I think, the nature of these things is once you start, it's very difficult to stop. Yeah. We will continue, yeah.
Okay. Yeah. It's like taking a penalty, I guess. Just sort of Elocta, clearly Germany is reimbursed for Hemlibra. Did you say that you see no indication of substances switching at this stage?
Yeah. We haven't found it yet. Normally, we don't comment even on a country basis, but the impact has been, let's say, what we can see has been very limited. What we see for sure is how many patients we have net gains. There's a positive trend.
Good. Yeah, that was all. Thank you.
You're welcome.
The next question comes from the line of Viktor Sundberg from ABG Sundal Collier. Please go ahead. Hello, Viktor. Your line is open.
Yeah. Can you hear me?
Yes, we can. Thank you.
Thank you for taking my question. On Gamifant, maybe you could add some reasoning around the raised peak sales projections. I guess as of now, the product is quite lumpy since it has a limited patient population, and you're in phase II, I guess, for secondary HLH. When would we expect a more stable or linear sales trajectory for that product? On Synagis, since the RSV season, I guess, is behind us right now, if I look at the CDC data, what do you expect from the first quarter since the peak of the season has sort of peaked? Could you comment if wholesalers have already stacked up in anticipation of that peak since before? Just a comment on Q1 would be helpful. Just a final question also.
Just in terms of what gives you most confidence that you could reach your sales target for 2020. Gamifant is still quite lumpy. On Doptelet, we haven't really seen the sales trajectory yet. Synagis will in some ways depend on the RSV season, I guess, for next year. Is it mostly hemophilia where you have the greatest visibility for your guidance for next year? Thank you.
Thank you. Let's start with Synagis. When you look at the product by season, basically we gave guidance to the market of $269 million when we bought it, this was a 2017, 2018 season. Last season, 2018, 2019, which basically ended in April, the business was around $ 276 million, already starting to benefit from the change of ownership. When you look at the 2019, 2020 season, we think that we can grow this franchise, and also in the last remaining two quarters of that, let's say it's mid-single digit. When you compute this, that basically gives you a view. There's always this inventory movement. The good news is that over the entire season, this becomes irrelevant because it's always flushed out towards the end. I think what we believe in a single digit.
With Gamifant, let's say, I think you need to realize, $56 million for a limited indication from a start. Yeah, it was lumpy, but it became a reality. Yeah. I'm actually confident and satisfied that this was actually a good launch. Yes. Would I have wished that this launch would fit into more of a spreadsheet of a linear model? I agree. It would make my life much easier; it would make your life much easier. It doesn't. It is dependent on the patient who's coming in. Now, there will be various trends. Obviously, the big trend is the enabling of secondary HLH in adults and in children. With the first readout of the MAS data that will come sooner. Basically, that's the regulatory pathway.
There is another pathway, which is the new definition of primary HLH, which basically says, in a nutshell, you do this by exclusion. Because there are data out that suggests that even patients with infection-related HLH have a genetic predisposition. As such, being classified as primary. There is a debate ongoing, and this is not as structured as other areas. The more the debate and their thought leaders in this area who are strongly advocating to think this way, the more the debate is swaying this way, the broader, let's say, the target audience for this business is going to become. I would say, towards the second half of this year, hopefully, we see a little bit less lumpiness. If that would lead to a significant growth versus previous year, I could even live with a bit of lumpiness.
I think the bottom line is Gamifant will be a significant contributor. Then you look at Doptelet entering into a significant category, and you come with a better product and with a sharpened organization into this year, you would assume that the challenger will take some share. I'm not saying that we will be already a leader, but that you take some significant share that should resemble then also in our P&L. There is a growth. Yes, it's not a guarantee. That's the reason why we also now investing into the product, investing into the development, into CIT. The more we invest into clinical experience, medical marketing activity, the stronger the halo will be, the stronger it will be clear that this product is clearly differentiated. That's really how we think about it. We think that hemophilia will be good for us.
I look forward to present to you the Q1 number. Whatever they will be. I think we are coming into this year with a broad chest.
Yeah. Just on Doptelet, do you have a full sales force in place for that product, or are you building that as we go here in 2020?
That's part of the investment. Part of the investment is commercial, and the other part is really R&D related, indication related, and medical related. Yeah, we have a full field force in place that is absolutely competitive in size and definitely also in qualification with best in class.
That sales force was not in place after June when the product got approved last year.
It was, to a certain degree in place. I would say the field force orientation, and we invested obviously in further expansions, there are more team members now on board. It is primarily also now the way we will bring in to be proven. That we are really better than the previous state. You would think that an organization that focuses on exit and not on sales, and that was a little bit, I wouldn't say surprised, but came to this launch in a little bit, in an accelerated fashion, was not so prepared. That this now should pay dividends. For the team, there's no excuse. We now will be on par, and we are convinced by the team. I met them all. We had a pretty large team event recently in the U.S., and they are fired up.
Okay, thanks.
You're welcome.
The last question comes from.
Yep.
The last question comes from the line of Christopher Uhde from SEB. Please go ahead.
Hi there. Lots of analysts these days. I just have some questions. First, Russia, what would be a typical time to reimbursement to launch, let's say, for rare disease products after approval? Can you share the switch rates for Elocta and Alprolix right now? I think I have some questions for Milan on Gamifant, but we can start with those two.
Basically, Russia will be a 2021 event. It takes around a year to get the price and then launch. We use now the time to prepare, obviously. The switch rate, we don't comment really on this. You've seen recently patient conversions that we have mentioned in the one or the other context. They provide you with a good orientation on how many patients we are gaining. Maybe then I give the floor free to Milan. Maybe you fire off your second question, Christopher.
Okay. For the, I guess, secondary HLH in kids, how does the initial dosing and dose escalation compare to what was done in the registration trial? Can you also comment what proportion of those patients are getting stem cell transplants? Also, what was the reason for the delay for the secondary HLH study in adults, please?
Yeah. The secondary HLH study in MAS has a starting dose of 6 mg per kg. We have very good response rates from that study. I can't really comment on transplantation. When it came to the adult study, we are doing everything we can to get it started. We have the approval to get started at the first site, and now we're waiting for the first patients to enter, hopefully.
Great. Thanks very much.
Christopher, I hope our answers were complete, yeah, hopefully.
Yeah. That's great. No, I would ask one last question actually about Synagis. Last, I guess, when you got the rights, you commented that there was not the usual price increase in 2019. Have you secured that for 2020, something more in line with historically?
Yeah. We have secured this.
Okay, great. Thanks.
You're welcome.
Thank you.
Thanks a lot. Yeah. Appreciate it. Yeah, thanks everybody for your interest. It was an exciting year, and I hope 2020 will be not less exciting. Appreciate it. Yeah. Thank you.
Thank you. This now concludes our presentation. We do apologize for any sound issues you may have experienced. The full presentation will be available on demand in a short while. Thank you all for attending. You may now disconnect.