Welcome to the UCB full year 2022 capital market call. My name is Antje, and I'm heading Investor Relations at UCB. Before I introduce you to the agenda today and hand over to the speakers, I'd like to make two remarks. This video conference is being recorded. This presentation and the following Q&A session are covered by the disclaimer and Safe Harbor statement as stated on slide two of this deck. Please kindly read this carefully. With this, I'd like you to introduce you to our speakers today. We will start with our CEO, Jean-Christophe Tellier, followed by our Chief Medical Officer, Iris Loew-Friedrich, and she will hand over to our Head of Neurology, Charl van Zyl, who will then turn it to the Head of Immunology, Emmanuel Caeymaex. The conclusion will be done by our...
The financial conclusion will be done by our Chief Financial Officer, Sandrine Dufour. Jean-Christophe will finally briefly conclude this presentation before we hand over to the Q&A session. For the Q&A session, please type your questions into the chat, or if you prefer, email it to me under antje.witte@ucb.com. I will ask the question on your behalf to the presenters. With this, I kindly hand over to Jean-Christophe. Over to you.
Thank you, Antje. Good morning, good afternoon, everyone. It's a pleasure to welcome you at our call. Thank you for your interest at UCB. Next slide, please. In a challenging year, UCB demonstrated resilience, delivered strong results. Is now ready to execute on the multiple launch ahead. As we communicated earlier, the result that you see here on the top of the slide is at the high end of the guidance, even a little bit more, a little bit above, with revenues at EUR 5.52 billion. Underlying profitability at EUR 1.6 billion. These strong results are built first on the success on our core growth drivers, such as Briviact in epilepsy or CIMZIA, which have reached already two years ahead of the plan, excels of more than EUR 2 billion of revenue.
They are also the consequences of the successful acquisitions and integrations of Zogenix, which gave us Fintepla. Fintepla contributed already in 2022 to our growth and our revenue with an amount of EUR 116 million. Finally, the cost control rigor and discipline in our resource allocation give us the ability to protect the investments towards future launches while being able to deliver the result that you see here. We are now ready to move full speed into the executions mode of the launches, as you can see on the bottom of the slide, with the various indications for Bimzelx and the three new assets that we have already with, as Fintepla, or we will launch in Myasthenia Gravis.
The solid performance, the strength of the platform that we have built year after year, as well as the confidence on the in the future, give us the guidance that you share, we share with you today of revenue expected between EUR 5.15 billion and EUR 5.35 billion, and adjusted EBITDA between 22.5% and 23.5%. Next slide, please. Sustainable performance is also the result of progress on extra financial elements, and key component of that is, continue to ensure access to our solutions to a broader populations of patients who need our solution. As you can see here, we have made good progress in all of the three indicators that we are continuously monitoring to evaluate our access for our medicine for the patients.
These are, of course, key component as our objective is, of course, to deliver value for patients wherever they are. Next slide. Sustainable performance is also the result and the consequences of other key financial elements, such as the value for our people, the value for the community where we operate, and the value for the planet. You can see here some of the key component of all of these three indicators that we are monitoring year after year to make sure that we are integrating that into an overall performance evaluation. Both pillars, financial and extra financial, are key for the long-term success of the company. Next slide, please.
In a nutshell, continuing to focus on the patient's value that we want and aim to deliver, following our objective of being inspired by patients and driven by science, with the strong platform that we have and the confidence in the future, we are ready to start a new phase of growth. After years of transitions linked to the loss of exclusivity of certain of our products. As you can see here, we have three products to launch in the neurology space, and we have new indications with within the rheumatology and dermatology on ive meds. We are very confident that with the good preparation that we have, we will be able to move full speed into this phase.
With that, I would like to thank you and hand over to Iris, she will go deeper into these evolutions of the pipeline. Thank you.
Yes. Thank you very much, Jean-Christophe. What a unique phase in UCB's history. We are so excited as we turn the many positive phase 3 results of last year into regulatory submissions around the world. This high intensity of regulatory submissions and reviews will translate into many launches. We are very thrilled by the opportunity to make an impact on the lives of so many patients. Next slide, please. Just take a look at this slide and the abundance of regulatory events. In the middle bar, we cover our ongoing regulatory reviews in the U.S., European Union and Japan, which we expect to translate into approval soon. At the bottom, you see the upcoming regulatory submissions. We have two huge waves rolling, covering four molecules and eight patient populations. Amongst them are Bimzelx, bimekizumab, in several indications. Rozanolixizumab and zilucoplan for patients living with generalized myasthenia gravis.
Fintepla for patients with Lennox-Gastaut syndrome, just approved in Europe. Please do enjoy with us the prospect of several expected approvals and launches every quarter, and new submissions following on the heels of the approvals expected to lead to more approvals and more launches in the future. Can you imagine so many important events in such a short period of time? Next slide, please. In addition, we are enjoying a very remarkable clinical stage pipeline with five phase 3 development programs, four innovative phase 2 programs, and new efforts moving into phase 1. With such a wealth of opportunities, please allow me to focus on a few milestones. Following the very strong results in generalized myasthenia gravis, rozanolixizumab development is progressing in patient populations that have no proven specific treatment options and serious unmet needs.
We are very hopeful that patients living with MOG autoantibody disease and patients living with LGI1 autoimmune encephalitis will benefit from rozanolixizumab in the future based, of course, on the data that we are currently generating. These programs are ongoing as planned. We have added a study in severe fibromyalgia to the portfolio of new indications with rozanolixizumab. Non-clinical data suggests a role of autoantibodies in the disease biology of fibromyalgia. However, as always, please remember that proof of concept studies are there to explore novel mechanisms of action in uncharted therapeutic territory, so with a completely open outcome. To bring the benefit of Fintepla to patients with unmet medical need, we are recruiting children with CDKL5 deficiency disorder into a phase three study. These children are suffering from catastrophic seizures, developmental delays, and have no valid treatment opportunity today.
The combination of deoxycytidine and deoxythymidine, we abbreviate it as DOXTM. You might remember that we previously referred to this combination as MT-1621. DOXTM ensures survival of patients suffering from the ultra-rare Thymidine Kinase 2 deficiency. We have now reached alignment with FDA and EMA on the submission strategy for DOXTM, so that regulatory submissions can commence and will commence in 2024. Our phase 3 programs with dapirolizumab for people living with systemic lupus erythematosus and with Staccato Alprazolam for the acute termination of stereotypical prolonged epileptic seizures are ongoing as planned. Top-line results for these two programs are expected in the first half of next year. Patient recruitment has been completed for our disease-modifying proof of concept studies in neurodegenerative diseases.
With the tau antibody bepranemab in patients with mild Alzheimer's disease and with the small molecule alpha-synuclein misfolding inhibitor, UCB0599, in patients with early Parkinson's disease. We are now expecting top-line results in Q4 2024. Both are very comprehensive proof-of-concept studies, now with dose ranging embedded in both studies. 450 patients participate in each study, and we have 18 months observation periods. That's actually really what it takes for proof of concept in neurodegeneration. Again, as recruitment is completed, we will have results in the end of next year. In addition, I am very pleased to inform you that we have initiated two phase I programs with two molecules with different mechanisms of action in atopic dermatitis. This illustrates that we have a growing number of promising preclinical molecules.
We are able to replenish the pipeline from the very early stages while also delivering on our differentiation ambition. Next slide, please. Let's focus for a moment on our two near-term opportunities to serve patients with generalized Myasthenia Gravis, gMG. Please remember that the unpredictability of exacerbations and the fluctuating nature of the disease belong to the most burdensome token of gMG. Planning activities of everyday life is impossible for patients because they never know when and how their disease will take control of their life. In addition, patients are very severely impacted by fatigue, so badly that they often cannot get up in the morning and fatigue preventing them from working and from participation in social activities. Walking, talking, eating, all these basic activities can be massively impacted by gMG and contribute to patients' severely reduced quality of life. What can we offer them? Next slide, please.
The MG-QOL15r score is a widely recognized patient-reported outcome measure. The 15 questions cover all dimensions of gMG, from walking, eating, to working, socializing, driving, well-being, and depression. It is a very patient-focused instrument. The graph illustrates the longitudinal course of the MG-QOL15r over time in patients treated with zilucoplan, initially for 12 weeks versus placebo. The patients on placebo switched over to active and showed similar efficacy. For all patients, the profound improvement with zilucoplan continued throughout the entire treatment period. These are very meaningful results and very much in line with expectations from the mechanism of action. The data directly reflect the positive long-term impact of zilucoplan on relevant activities of daily living. That's what truly matters to patients. Next slide, please. Let's have a look at rozanolixizumab.
MG-ADL is the primary endpoint of our registration study, and we've measured the difference from baseline to day 43, the end of the first six-week treatment cycle. The overall results are very strong and robust. You know that already. These graphs illustrate now the two different patient populations in the study. Those who are positive for acetylcholine receptor antibodies on the left, and those who are positive for MuSK antibodies on the right. The patients with MuSK autoantibodies represent about 15% of the overall gMG population. The efficacy in both patient populations is strong across both doses of rozanolixizumab tested. However, it is the first time ever that efficacy of this magnitude has been observed in patients who are MuSK positive. The efficacy is consistent across all efficacy parameters in the study with the largest number of MuSK-positive patients recruited to date.
What you see is unprecedented efficacy of rozanolixizumab in a very relevant subpopulation. Next slide, please. I mentioned before that debilitating fatigue is one of the key symptoms of gMG that has huge impact on patients' ability to function effectively. In UCB, together with patients and with experts from academia, we developed patient-reported outcome measures that explore the different types of fatigue. There's, of course, muscle fatiguability that you would expect in a disease where the neuromuscular junction is affected. However, there's also physical fatigue, the deep lack of motivation and energy that is so frustrating for patients. There is bulbar muscle weakness that results in inability to swallow, in difficulties to articulate and to speak properly, in weak jaw and face muscles impacting mimics and facial expression. All these are very critical factors contributing to quality of life.
You see in these graphs the profound impact that rozanolixizumab has on all three dimensions of fatigue, very visible during the six-week treatment cycle. These are huge and very meaningful improvements, uniquely demonstrated for rozanolixizumab, clearly indicating the promise of this treatment opportunity for people living with gMG. With these prospects and attributes, I hand over the baton today and in the long term for successful launches to Charles. Charles, please, over to you.
Thank you, Iris. Also thank you everyone for joining today's call. Of course, it's my pleasure to share with you our progress in neurology. Before we go deeper into some of the results, I want to leave you with two very important messages. The first one being leadership in epilepsy, in our view, is secured for the next decade. Of course, we are very pleased also with the progress we're making on preparing our launches in the space of Myasthenia Gravis that will roll out in the second half of this year. If we go to the next slide, and we go a bit deeper into the results.
Of course, we are very pleased with the results that we see in epilepsy, with strong growth that we see from Briviact and of course Nayzilam, that are important areas of protected spaces in our portfolio. Strong growth against competition there and really foundational of course for our future growth in epilepsy. We've also, of course, gone through the loss of exclusivity of Vimpat and Keppra. We see a large component of that in a sense behind us as an effect of 2022. There will be a remainder of the loss of exclusivity in the first half of this year. Of course, we return to growth more in the second half of this year as an enterprise. We've also done some rigorous resource reallocation to, of course, our growth drivers in epilepsy, but also to prepare for the launches in Myasthenia Gravis.
I'm of course, also very pleased with the progress we've made on the integration of Zogenix and the performance we see of Fintepla in the market, and I will speak more to that in short order. Very solid results, solid foundation, this transition we are going through, and very pleased, of course, with the growth that we see from our protected portfolio. If we go to the next slide. Again, I want to remind you of our very diversified strategic position we in a sense have in neurology. We have a very core focus on epilepsy, and with the advance of science and the better understanding of the genetic pathways, we are seeing a greater movement into the spaces of rare epilepsies with the advances of science.
This is an area we will continue to explore and of course, also the important component of our research focus in the future. The second important area of future growth will be a new space for us, of course, in the space of Myasthenia Gravis with neuroinflammation. Of course, there are other patient populations that Iris have mentioned that will of course expand our growth opportunity in this space. In the third pillar of our strategy, neurodegeneration, where disease modification is a key component of outcome. Here we have essentially partnered our great science with of course two important partnerships with Roche in Alzheimer's and with Novartis in Parkinson's. If we go to the next slide. I really want to build here a bit further on what leadership looks like in epilepsy.
Of course, what you see here is a history of 20 years, you know, the large number of patients we serve, the breadth of our clinical programs, the focus on publication. Really a presence that we have built and legitimacy that we have built over significant time. Underpinning all of this leadership is essentially key components that I just want to highlight very briefly. A very compelling portfolio we have with Nayzilam, Briviact, and Fintepla being important growth drivers now going forward. Keppra and Vimpat of course facing loss of exclusivity, but still serving a large volume and population of patients. We have of course made very strategic and smart acquisitions with Zogenix and of course with Engage Therapeutics that brought us Tacro, Alprazolam into our pipeline.
In the space of discovery and early work on future spaces of rare epilepsies, we have engaged in different academic partnerships to continue to further our understanding of this space and potentiate our pipeline for the long term in the spaces of rare epilepsies, where there's still a high degree of unmet need. In the broader sense, we also focus on how we can help patients with the overall disease management with very smart investments in digital health that essentially help patients to monitor seizures, but also in potential to be able to detect seizures in the future.
This is a clear picture of our future in epilepsy and one that of course we're very proud of and very confident that we can continue to see this as a cornerstone for epilepsy and for UCB in the future. If we now go to the next slide, I wanted to just build on what Iris had mentioned in terms of Fintepla. Here you see the three core patient populations that will be the cornerstone of our future in Fintepla and what makes us very confident in the ability to release our peak sales and predict an EUR 800 million peak sales as we've done earlier this year. The common theme with all these patient populations is a high degree of uncontrolled state with a high frequency of seizures.
The second important component that is, of course, very severe here is the risk of sudden death in epilepsy. The importance here of having a solution that is reducing seizures is of course key, and this is what we have in Fintepla. It's really establishing itself as a foundational therapy in Dravet. We are now re-launching Lennox-Gastaut and rolling that out as a new patient population where we see significant potential. And in CDKL5 deficiency, we are able to read out our results in phase three in the first in the second half of 2024. Very important foundational elements which make us very confident to predict an EUR 800 million peak sales as we have stated earlier this year.
If we go to the next slide, I want to just spend a little bit of time on our preparation for Myasthenia Gravis with the launches that are coming up in the near term. First of all, I think we started the year with great news, the priority review status for rozanolixizumab with the FDA. This is a clear signal of the quality of our submission and our data, of course, we are pleased with that accelerated review and of course, accelerated launch potential as well. We are working across four key levers. There's of course, a very high unmet need in this space, we know others have entered, but with our targeted solutions, we see the potential to continue to address a large number of patients with high unmet need.
We have a very differentiated portfolio with two assets that I will speak to in a short while that give us really the potential to for patients to take control of their disease as opposed to the disease taking control of them. We are also working closely with sustainable access. We know this is important in this space. This is a chronic condition and how we can ensure that there is sufficient reimbursement and affordability for patients to have access to these medicines. Finally, the patient experience is very important. This is a chronic condition, a lifelong condition, and that relationship with our solutions and with the patient is very important, and we want to make this seamless for patients when they are on our treatments going forward. Very pleased with the progress.
Of course, a more accelerated launch potential now in the U.S. that we are gearing up for, but confident with where we are and how we see that rolling out in the second half of this year. As we go to the final slide, I just want to again emphasize a few points which we shared with you in the past around the positioning of our two assets. On the left-hand side, you see the standard of care today, which is often high doses of steroids or non-steroidal immunosuppressants. With chronic use of these high doses, of course, there are many side effects. This is in a sense the testament of these treatments really not being targeted to the underlying cause of the disease.
With the entrance of these two mechanisms of action, complement inhibition and FcRns, we are able to really address different needs for patients with clear needs of preference that patients might have or preference that physicians might have for how they would choose these two therapies. For zilucoplan, we see a very strong foundational maintenance therapy potential to manage control of the disease. With FcRns, as Iris had indicated also, we see a more cyclical use of these treatments. We see these FcRns in particular rozanolixizumab being also a disruptor of course to IVIG today. The important differentiation of having also MuSK positive indication will be important component that we see that will differentiate rozanolixizumab in this space.
Again, I want to thank you for today's attendance and leave you with these two important messages again, that we're feeling very confident with our leadership position in epilepsy and of course, gearing up with great confidence also in launching Myasthenia Gravis in the second half of this year. With that, it's my pleasure to hand over to Emmanuel.
Thank you. Thank you very much, Charles. Welcome everyone. It's gonna be my pleasure now to give you some details as to our expanding portfolio in immunology with three growth drivers. Cimzia of course, and you heard about us exceeding the two billion peak sales target that we had set several years ago, with continued strong volume growth. Also Evenity. Evenity is a brand which last year really had an inflection in its growth rate. Finally, the launch momentum with Bimzelx, and I'll detail some of the strong exit numbers that gives us a lot of confidence for the performance with Bimzelx in 2023. Moving to the next slide, just looking at the portfolio again.
Starting with CIMZIA, of course, we drove growth in volumes by 8% last year and 5% at constant currency. It is a brand which continues to grow in volumes at an accelerated rate, in particular in international markets, but also in the U.S. and Europe. With having exceeded EUR two billion, of course, we're looking forward to continuing that growth. The goal, of course, will be to maintain volume growth ahead of price erosion for the next year or two. With Bimzelx, we've had strong expansion in access this year and there's strong launch momentum, which I'll detail in a few minutes.
Finally, with Evenity, you have perhaps heard from the Amgen investor call recently that the brand now is an $850 million brand if you look at in-market sales across the world. It's really contributing significantly to UCB in the other operating income line. The contribution has increased by close to 60% in 2022 versus 2021. We've launched in Europe, we've booked some major access gains towards the end of the year, in particular in Spain, which is the third-largest bone builder market in the world. With this, we're really confident about this portfolio growing with three drivers for 2023. Let's focus on Cimzia on the next slide.
You see here how we've grown Cimzia over the years to exceed EUR 2 billion and in fact exceed one million patient years of exposure. You can see in value that, of course, the U.S. represents more than half of our sales, that is about 58% with the prefilled syringe and close to 40% with the lyophilized formulation. As mentioned earlier, we enjoy strong growth in international markets as well as Japan. Cimzia has established a level of leadership in women of childbearing age, where about 40% of our new patients joining Cimzia are of that demographic.
Just to take an example in US rheumatology, the existing patient base is about 1/3 women of childbearing age, which is more than double what you would expect, based on rheumatoid arthritis and spondyloarthropathies, demographic facts. A lot of the growth with Cimzia comes from psoriasis axSpA, and that sets us up for success with Bimzelx, of course, as we're interacting with the same audiences. Let's move to the next slide and dive a little deeper in Bimzelx. I have three slides to show you. First of all, what you're seeing here is the uptake in number of patients cumulative over the first nine-16 months in Europe, in Canada and in Japan.
You can see that Bimzelx, in terms of uptake, is situated somewhere between the last 2 IL-17 launches and the 2 large IL-23 launches. Of course, this was a launch that occurred in the pandemic for the first markets, namely Germany, the U.K., and Japan, which is still somewhat under restrictive conditions. We see those curves starting to lift up even in the first months when we're adding the numbers of patients relative to other launches that we've been able to gather in countries like France, Belgium and other European mid-markets, and soon the south of Europe. If we wanna have a kind of a more recent view, I would suggest we turn to the next slide, which is actually showing you how we're performing in the IL-17 segment.
You remember from a year ago that our goal is first to lead in the psoriasis IL-17 segment and from there on to expand and displace other products in psoriasis and also expand beyond psoriasis with psoriatic arthritis and axSpA, which are to come this year in Europe and in Japan. In July, I shared figures with you in terms of the dynamic share of Bimzelx in this IL-17 psoriasis segment. For example, we had more than 15% share in Germany, more than 20% in the U.K. You see those numbers have evolved, and we're now at 30% dynamic share in Germany, 25% in the U.K, 33% in Canada, where Bimzelx is actually leading in terms of new patients in the IL-17 segment of psoriasis.
Is also growing the IL-17 segment as a proportion of the total. In France, we've had an impressive launch with more than 20% of the new patients in the 17 segment just four months after launch. Of course, we fully expect all those numbers to continue growing. This gives us a lot of confidence that we are on track to become the leader with Bimzelx in psoriasis IL-17 products, and we've achieved this in a number of markets. I mentioned Canada. There's also Belgium, Sweden, and there's more to come in the next few months. Now, of course, the question is: to what extent are those patients accumulating to transform this leadership in new prescriptions, in total prescriptions and in values? The next slide is an attempt to give you a bit of a lead indicator to that.
That is the actual persistence in real-life practice as measured by pharmacy data, in one of the two markets where we have the most patients, namely Germany. You can see that in Germany, after six months, 88% of the new starters on bimekizumab were still on bimekizumab, and that was close to 70% at month 12. Now, of course, it's probably a conservative measure, but the measure is the same for all interleukins. In this case here, we've plotted the IL-17s and the IL-23s, and you can see that Bimzelx in clinical practice truly has different characteristics than other IL-17, as we've seen in clinical studies. You can also see that the persistence rates are remarkably similar with the IL-23 persistence rate, showing that patients are happy to stay on the drug.
With more data, I think this will be confirmed over the longer term. That gives us a lot of confidence ahead of launching in the U.S., both the fact that the intention to use Bimzelx is very high, the dynamic share is high, and the retention rate seems to be very competitive as well. Now let's move to Evenity, the third growth driver for the UCB immunology portfolio. Our goal with Evenity is first to achieve leadership in the bone builder segment, right? Think Forteo, Tymlos, et cetera. That's been achieved in a number of markets in the U.S. and South Korea, Australia, Canada, Belgium, Denmark, and the Netherlands.
We're getting closer in markets like Germany, for example, but also Japan, where we should be nearing that status, give or take, a half year or so. I mentioned earlier that the total in-market sales are $850 million. In terms of the net sales in Europe, they now stand at $25 million for this year. The big wins for the second half of this year in Europe were the uptake of Evenity in what we call kind of mid-sized markets such as Switzerland, Belgium, et cetera. We really had very rapid uptake there. But also unlocking access in Italy, in Spain, and gaining the NICE HTA endorsement. Those are big wins.
These weren't easy to obtain, to get the value recognized of a bone builder on osteoporosis is not easy, even with stellar data like the ones we have with Evenity. We've now achieved this, that sets up Evenity for very robust growth into 2023, as we will now be able to accrue patients across most of the continent. The next step, of course, with Evenity will be to expand the size of the bone builder market, we do this with our Fracture Liaison Services, ensuring that patients that had a fragility fracture first get treated to increase their bone mineral density before then being put on an anti-resorptive. We of course activate patients as well, through our partnership with Amgen, with use of DTC in the U.S.
All these things combined should lead to continuous strong growth for Evenity for many years to come. With this, I would like to hand over to Sandrine, our CFO. Thank you.
Thank you, Emmanuel. Good morning, good afternoon, everyone. I'm pleased to report on our 22 results. This was a year of multiple headwinds, both external macro environment and our own agenda. We managed to deliver financial results at the upper end, slightly above the upper end of our financial guidance as we had revised it back in June. Let me start on the next page with an overview of the net sales. This page is actually a recap of what Charles and Emmanuel have already explained. I will not go through all lines. The total net sales reached EUR 5,114 million. It's a 6% decrease, 8% decrease at constant rate.
Overall, we were pleased with the underlying solid growth, excluding the impact of loss of exclusivity, with healthy volume growth for Cimzia, for Briviact, for Nayzilam, for Evenity, as well as the launch dynamics with the strong launch uptake for Bimzelx that Emmanuel just presented, and the integration of Fintepla. The impact of the loss of exclusivity of two products more than offset this growth. It represented a headwind of more than EUR 800 million since the inflection points of their respective peak sales. Vimpat LOE trajectory was according to plan, while Keppra generics erosion in Japan was stronger than expected due to the multiple generics and the governmental support to generics.
Moving to the next page, before diving in the full P&L, I wanted to highlight how we contained the impact of lower net sales on profitability while continuing to invest behind the launches and the pre-launch activities. We successfully integrated Zogenix. We managed to limit the dilution to 2 % points of EBITDA margin. It's slightly less than anticipated. We had planned for a 2.5 % point dilution. We confirm that the acquisition will be earnings accretive this year. We have also been very intentional on our costs, you know, to create the necessary space to adequately resource our ongoing and upcoming launches by being extremely cost discipline, particularly because we were also hit by higher inflation.
We are executing our transversal program that we call Focus for Growth internally, that aims at driving sustainable efficiencies and allowing value-based resource allocation. In 2023, we are expanding the scope of the cost categories which are covered by the program, the program itself will be fully deployed. As mentioned, we had to face unexpected inflation on our cost base, including particularly the high indexation on Belgium wages. This, coupled with the impact of the Complete Response Letter back in May, that led to a company-wide reinforced cost discipline throughout 2022. We've pulled some marketing and selling resources from more mature products. We reallocated them behind the new products. What does that mean when we look at the P&L? We can go now to the next page.
Net sales evolution was the key driver, and the revenues of EUR 5.5 billion decreased by 4%. Adjusted gross profits of EUR 4.2 billion decreased by 6%. This is in line with the net sales performance. The adjusted gross margin decreased by around 1% point to 77% with the write-off of some Bimzelx inventory. Total OpEx grew by 5%. It's only 1% at constant rate. That takes into account as well the integration of Zogenix. Marketing and selling expenses grew by 11%. It's 3% at constant rate. As mentioned before, we've reduced the investment behind mature and genericized products to create space for reinvestment in launches of Fintepla, of Evenity, of Bimzelx, and the preparation for Myasthenia Gravis. R&D was EUR 1.67 billion. It was flat at constant rate.
The total represented 30% of revenues. It reflected the progressing pipeline, the multiple regulatory reviews with the nine clinical stage programs, as well as the earlier clinical development. The termination cost of ITP were also integrated in this number. Other operating income integrated the net contribution from Amgen in the commercialization of Evenity. Emmanuel highlighted this. This is EUR 240 million, a growth close to 60%. This was partly compensated, among other, by some write-offs of receivable. Overall, adjusted EBITDA ended up at EUR 1.26 billion, corresponding to a 22.8% margin, of which 2% point dilution linked to the Zogenix integration. That is a 23% decrease versus 2021. Below EBITDA, the profit decreased to EUR 418 million.
It was impacted by the acquisition of Zogenix, with higher amortization of intangible assets due to the addition of Fintepla, higher restructuring expenses relating to the acquisition, and higher net financial expenses, which are linked to a higher net debt, but also financial expenses being impacted by higher interest rates. On the other hand, the tax expenses decreased in 2022 compared to 2021, and the average effective tax rate was 17.8%. Core EPS, based on core profits excluding one-off and other adjustments, were EUR 4.37 and decreased by 33%. All in all, we managed to contain the impact of net sale decrease and other headwinds on the overall profitability. If I move to the next page and we look at balance sheet and cash flow.
Balance sheet remains strong with, of course, the impact of Zogenix on the net debt. Net debt ended at EUR 2 billion and a ratio of net debt on EBITDA at 1.6 times. If I exclude Zogenix, we had a very good cash flow generation, and you can see on the bottom right chart, our cash position ended up at a comfortable level, close to EUR 900 million. Our board of directors will propose EUR 1.33 of gross dividend to our next AGM. It's a 2% growth versus last year dividend, and it is in line with our dividend policy. It also shows our confidence in the future. Moving to the next page on the extra financial performance. We were again recognized this year for our ESG performance by key ESG rating agencies.
In 2022, we improved the MSCI rating, moving from A - AA. We maintained our low-risk Sustainalytics score of 16.8. We are among the top-rated companies in our industry, and we also maintain the scores of the other ESG ratings. Last week, we've been selected to be part of the BEL ESG Index, which was newly created by Euronext, which is based on our good Sustainalytics rating. If I move to the next page, I now look at 2023 and our financial guidance. We are expecting revenues to be between EUR 5 billion 150 million-EUR 5 billion 350 million. EBITDA margin range of 22.5%-23.5%. If I start with the revenues, I will start looking at the trends.
I will start by the positive, supporting trends. We will see an increase in contribution from the ongoing launches and the expected multiple launches, including the launch of Bimzelx in the U.S., for people living with psoriasis. We also expect the continued solid growth of Cimzia, Briviact, Nayzilam, Evenity. On the other side, revenues will be impacted by the annualized impact of Vimpat's loss of exclusivity, both in the U.S. and Europe. I also want to indicate that the LOE effect will be more pronounced in H1 comparing year-over-year, while H2 should benefit from higher contribution from launches. These contrasting trends will drive very different top-line trajectories in H1 and H2. Now, EBITDA margin is expected between 22.5%-23.5%. This is taking into account a positive earnings contribution from Zogenix.
It is in line with what we had guided when we made the acquisition. I will come back in a minute on how we intend to manage the year. This translates into a Core EPS guidance of EUR 3.40 - EUR 3.80 per share, with a tax rate expected around 20%, as well as higher financial expenses, which is linked to the increased interest rates and the higher cost of debt. On the right part of the page, you can see the achievements in peak sales for Cimzia, Vimpat that has been delivered ahead of plan, the estimated peak sales for the future sales of Briviact and Fintepla that we have announced at the beginning of the year, expected to reach EUR 800 million by 2027.
Now, pausing a bit on how we intend to manage the year, looking at the next page. 2023 is a year of execution. Execution with multiple launches and launch preparation. The first key message is that we have adequately resourced all these plans to be successful to maximize the impact of our drugs. We know as well that we will take the Vimpat LOE annualized revenue drop and inflation net impact is expected to be higher in 2023 than in 2022 year-over-year. This is why we will continue to actively manage costs to create further efficiencies, to absorb inflation, and to be very disciplined in resource allocation. Beyond cost management, we continue to manage our portfolio as we have regularly done in the past, and we will focus on our core growing assets.
In January, we have sold an established brands portfolio of five medicines which were commercialized in Europe, and this sale has a small positive impact on the margin, which is reflected in the guidance. Last, we expect R&D to be about the same in 2023 as in 2022. After the successful completion of six phase 3, we are progressing six other phase 3 programs. We're progressing our earlier stage pipeline, and we have reached submission and post-approval activities, as Iris explained. Overall, we expect 2023 to be the platform on which to build a stronger midterm growth. That takes me to the next page, where we are reconfirming our 2025 ambition. We're confident about the future.
The 2025 ambition is at least EUR 6 billion revenues based on new product performance, overcompensating the LOE impacts, Bimzelx in five indications, Fintepla in two indications with the peak sales we've mentioned, rozanolixizumab, zilucoplan in generalized myasthenia gravis, and a low-to-mid 30s adjusted EBITDA margin, which is driven by the mix, the product mix, which is going to improve the adjusted gross margin and the operating leverage, where we are expecting marketing and sales and R&D to decrease as a percentage of revenue. I want to continue to highlight the strong Evenity margin as well. We are also expecting to continue to improve our ESG rating performance. With this, let me hand over to Jean-Christophe for closing remarks.
Thank you, Sandrine. Thank you very much. At the end of this call, I would like to leave you with few very simple messages. The first one is that in 2022, we have managed headwind with resilience, rigor, and discipline. Because of that, we have been able to deliver strong and solid results as well as we have been in a situation possible to prepare future launches. We are now on track to make sure that we can move into this execution phase and deliver future growth with this new portfolio in our hands.
This confidence in the future as well as the strength of the platform that we have built and the solid foundation that we have on the portfolio should give you the confidence that UCB is ready for the next phase of growth now in the future and delivering value for all stakeholders. With that, I would like to thank you for your attention and open the floor to the questions and get back to Antje.
Thank you so much to all presenters. Thank you, Jean-Christophe. I have a lot of questions for you, stay tuned. The first question is coming from Stacy Ku. How should we think about the higher or lower range of your 23 guide, revenue guidance? What are the different dynamics we should consider? Is it Bimzelx, Cimzia, et cetera? Second, could you discuss the investments into the commercial infrastructure for Bimzelx and Myasthenia Gravis launches? Can you provide some additional details around recruiting talent, what side sort of backgrounds they might have to execute on these launches? A third question, if I may, for Stacy Ku. As we await approval within the U.S. for Bimzelx, can you speak to the payer preparation that is ongoing for commercialization, position in formularies, and what do you need for additional indications?
Do you need to wait for additional indications for better positioning? The last one, for Fintepla launch in Dravet syndrome and Lennox-Gastaut syndrome, what are the patients coming from? Are these patients switching from other branded agents or generic drugs? Would you be willing to comment on early penetration rates for Fintepla within Dravet and Lennox-Gastaut? How should we think about the competitive dynamics? I think the first question goes to Sandrine, and the second as well. You might want to share a little bit with the talent recruitment with Charles, and then it goes to Emmanuel on Bimzelx and ends up with Charles. You can merge as you like it. Sandrine.
Yes. Thank you. Thank you for the question. I will start by the underlying dynamics of the revenue guidance. I mentioned, you know, the clear supporting trends with the launches, the continuous growth of our portfolio and on the negative, the annualized effect of the loss of exclusivity. How do we look at the range? You know, we always enter the year with a list of risks and opportunities. Of course, with the launch, there's always some trajectory questions. There are always also some potential price or gross to net effect.
I want also to maybe point the effects potentially, where, as you know, we have a policy to hedge one year in advance our cash flow to protect the EBITDA guidance in terms of real rates, but we are still exposed at the level of the top line. We also take this into account when we calibrate the range of the guidance. I would like to say that versus the previous year, the width of the guidance is narrower because we're not in the same situation. We are now the trends and trajectories of the LOE behind us, so this is less of a risk.
On your second question on the investments into the commercial infrastructure, you know, I think in the recruitment, I will let my colleagues comment on that. What I want to insist upon is that it's definitely something for which we have prepared and planned in the plan for the OpEx in 23. No doubt that we are fully equipped to hit the ground and be very effective on the market. I don't know if Charles and Emmanuel, if you want to comment on the recruiting talent.
Thank you, Sandrine. I'm happy to comment on myasthenia gravis. First of all, of course, in the rare disease space, we've been able to attract 70% - 80% of our talent coming from other rare disease companies with rare disease experience. We're very pleased in a way that we are attracting top talent, especially also in the US environment. We have resourced to lead in this patient population, we're confident with what we have now. We have, of course, mapped out the key centers, the coverage we need to have and, you know, the infrastructure on the ground. This is well-funded and in place to be ready to launch in the second half of this year.
I don't know, Emmanuel, if you wanna build anything further on that.
Yeah. Thank you. I'll build on that and take the US access question. In, in terms of talent, we've built out our dermatology teams a while ago now, and of course, most of those teams are now launching. They're a mix of internal talent and people with specific dermatology autoimmune experience, or at times also autoimmune in the broader sense. We've also acquired talent with consumer marketing experience, in particular in the U.S., when it comes to DTC and specialty pharmacy and patient services programs, as well as digital and people with payer experience as well. You know, the way to think about this is that for psoriasis and axSpA and PSA from a fixed cost point of view, most of those costs have been in our P&L for this year.
Of course, it could increase a bit as we launch in PSA and axSpA. Then variable, it's mostly gonna be driven by the U.S. and potentially DTC costs, which wouldn't come before the end of this year if we were to gain approval towards Q2. In terms of US payers and Bimzelx. You know, indeed, first line access today is very expensive in the U.S., and one really needs to build volume to be able to accrue the bargaining power to get decent rates for first line access. In that sense, additional indications will help, although it's not a necessary condition. The strength of the uptake will be an important factor.
At this point, we would expect the vast majority of our patients to be patients who have already failed on one or several biologics or newer oral drugs. Therefore, our focus has been to obtain single or double step edited access with all the large payers. Also to make sure that the new to market block is removed, meaning that there is coverage for the majority of lives from the approval onwards. It's looking good in that sense. I think the payers have had the opportunity to learn about Bimzelx data and experience, not only in psoriasis, but also our most recent data sets in other indications. I hope that answers your question.
Thank you. Charles, would you mind to continue on the Fintepla question?
Thank you, Stacey, for that question. First of all, typically in this, these patient populations, these treatments are more add-on treatments, so patients are already on a number of antiepileptic drugs. In this case, for Dravet, we are positioned as a second add-on, where patients are not failing or not able to control seizures. In Lennox-Gastaut, we're typically third line after Epidiolex. What we learned, certainly in LGS, which is a larger patient population and more heterogeneous, that about a third of those patients anyway have significant seizures. We see our share of that patient population, of course, as important because of the seizure potential or seizure reduction potential that we see with Fintepla. Just to make a few quick comments on our penetration so far.
We expect at least at peak, that we have 40% share in Dravet and 15% patient share in LGS. Where we stand today on a blended basis, and we can go a bit more in detail in a future call, is that we are roughly between 3% and 5% penetration so far. Very, very good with the early launches. Of course, this is predominantly U.S., and we expect Europe and other territories to come on board as well, as we go forward.
Thank you very much. The next question is from Richard Parkes, Exane BNP Paribas, this goes to you, Iris. He says, "I know you won't disclose specifics on the HS data, but maybe you could discuss broadly how you think it compares to other approved and development stage biologics we have seen in this and any differentiation you see." This continues, "The atopic dermatitis market is getting quite competitive. I know you won't disclose the target necessarily, but could you talk about what you think these assets bring to the table in terms of differentiation versus what's already out there?" His last question goes to Sandrine. "Guidance is for a 20% tax rate for 2023. How do you expect that to evolve going forward? Thank you.
Yeah. Thank you, Antje and Richard. In the light of the HS data, I think what you will see when they go public is that they follow the bimekizumab scheme that we have seen all along, deep efficacy and long-term maintenance of efficacy. We see that patients are improving. We see that patients stay on Bimzelx in the long term, as evidenced by the high rollover rates into our open label extension. For me, it's a continuation of what we have seen with Bimzelx all along. In terms of atopic dermatitis, yes, it's a little bit too early to disclose our mechanisms of action. You know, that it's very important for us that we address unmet needs in a meaningful and well-differentiated way.
This is how we select the mechanisms of actions that we target. This is how we select our molecules. Please rest assured that this has also been our guidance as we chose the assets for atopic dermatitis. The fact that we are bringing two forward shows you that we really have access to novel and, in our view, exciting mechanisms. Thank you.
I continue on the question on the tax, and maybe before answering beyond 2023, I just want to comment on 2023 guidance. As I read, there were also questions on that. The tax rate in 2023 is expected around 20%. There are no major changes versus 2022 in terms of regulation. It's mainly driven by a lower pre-tax earnings and the earnings mix, and that has an impact on the tax rate. Beyond 2023, as you know, there is this new international tax measures with the minimum 15% effective tax rate in the key jurisdictions, which is, of course, expected to have an upward impact on the effective tax rate.
Now, the new global rules do not foresee the abolition of the R&D incentives, and so far as well, the possibility to use the carry forward tax losses or patent box is confirmed. The legislation itself is not voted yet, so it's premature to give any guidance. What I can say is that if these were voted, it could help the tax rate in the near future, considering the unused tax losses and innovation income reduction that we have accumulated.
Okay. I'm continuing with Richard Vosser from JPMorgan. Stay on Sandrine Dufour. He's asking for if you could give him more details on the product already disposed in 2023, how much revenue should we remove? What so of gain should we model? What is the anticipated level of future divestments in 2023? Perhaps we start with Sandrine , then we go continue with Bimzelx and Emmanuel Caeymaex.
Okay. you know, we've done that very regularly in the past. We continue to optimize our portfolio and realize the value of some established brand if and when it makes sense, when they become too complex to manage or erosion is there. We manage the tail of our portfolio. As I said, we did this at the beginning of the year. The effect, which is captured in the guidance is very moderate, lower sales and on the bottom line, small positive impact. We are not commenting on potential future sales as this is something that we may do opportunistically. There is nothing which is baked in in the forecast that we have given to you today.
Thank you. Yeah, I saw other questions which I want to have this reassurance. Thanks for having this cleared. Richard Vosser likes to know from Emmanuel, what level of Bimzelx sales do you anticipate in 2023 in the U.S. And ex-U.S.? How do you see the US environment in which you are launching Bimzelx, given we have seen Cosentyx from Novartis has gone ex-growth already given the pricing pressure? He continues into Cimzia on the US rebates from the availability of Humira biosimilars this year. What additional pricing pressure are you expecting from payers? Of course, he goes back to Bimzelx now on the Bimzelx US approval. Do you need a further manufacturing investigation or I think inspection prior to the approval? If so, has it happened already? Emmanuel, please.
Thank you. In terms of the US environment that we were launching, as I mentioned earlier, I think there's a lot of competition for first-line pulmonary placements, but a lot of the patients are cycling and we see a big opportunity with Bimzelx and the kind of efficacy data, speed, depth, and durability that we've seen to enjoy fast adoption in the segment of patients that have already failed on at least one drug. Syndicated market research bears that out. You see about close to 40% of biologic prescribing dermatologists we see using Bimzelx in the first three months after launch and close to 60% within six months. I think the adoption will be quite fast. The understanding of the mode of action is there.
From an access point of view, I think we have a good plan. That's how we see it starting. Now, we're not giving indications as to the sales level for this year. I, what I mentioned earlier about the access that's been unlocked in Europe, including in Southern Europe, over the last few months, means that we're really gonna fire from all cylinders there. You know, I think the sales for Europe, Japan, and Canada will be a multiple of what we've seen this year, just because we're accumulating patients that failed the drug with opening new markets and with an increased capture rate of those patients.
You know, other than that, in terms of the access climate and the rebates, what I would say is that Cimzia is relatively immune to the pricing pressures generated by the changes on the Humira and adalimumab front, in the sense that about half our patients are lyo patients. We have first line in two populations in the U.S. in the commercial segment. One is the non-radiographic axSpA patients where Humira doesn't have an indication, and then the other one is with Optum. Those rates are already quite deep, so, you know, we don't necessarily see any expansion of the gross to net there.
I think for this year, the changes on the Humira front have been, in a way, an opportunity for health plans and PBMs to address the net cost of the class. Of course, we'll need to see what that means for 2024 and 2025. I'm not seeing any additional significant changes to what we've been working with over the last years.
Thank you, Emmanuel. Stay tuned. Florent Cespedes from Société Générale would like to continue, and he's again pushing for you to give some guidance for Bimzelx in 2023. How confident are you with the consensus for Bimzelx in 2023? He's quoting EUR 207 million. He continues, why despite good market penetration across the different markets, as shown on slide 27, you have been able to generate only EUR 34 million for 2022? Our products are not fully reimbursed. Any color you would appreciate.
Yes. Yes, thank you. Let me start with the second question. There is indeed in some markets we have a bridge, right? Patients are enjoying Bimzelx and are then transferred to commercial coverage. The example here is Canada, where we have about 1,000 patients on Bimzelx already. What we're seeing is that the time to transfer to paid commercial coverage or paid public coverage, that takes a while. We have secured access in the vast majority of Canadian lives now. We're expecting the majority of those patients to convert quite rapidly. That's one example. I think the other point maybe concerning Europe is that it's an area under the curve question, right? Our exit in terms of dynamic share is very strong.
You've seen the difference between July and December. Of course, we haven't been able to enjoy this level of new patients acquisition in the first half of the year. It really ramped up after the pandemic restrictions were lifted. Also, frankly, with more activity, a better understanding of what Bimzelx means in real life, right? The feedback of patients about the clear skin within weeks of treatment has been very impressive. That's explaining why you see the numbers that you see. It's also, I think, giving us a lot of confidence for how 2023 will look like, as I described earlier. What was the first question, Antje? It was related to the U.S.
No, how confident you are?
Oh, yes.
Bimzelx consensus of EUR 207 for 2023, and if you want to comment on that.
Yeah. I'll take the previous question on the inspection as well, because my answer here is that I'm very confident about that number. Of course, it all depends on the date of approval. So if we're hitting our PDUFA within Q2, then I think we're well positioned. In terms of the inspection, you know, it's the FDA's decision whether they want to inspect or not. So we're waiting to hear from the FDA, and. It's all within the six-month period that they've given themselves to be able to conduct an inspection if they so decide.
Okay. Thank you. The next question is coming from Graham Parry from Bank of America. Sandrine, EPS guide is below consensus despite better revenue and EBITDA guide. Can you talk through interest and tax expectations? What % of your debt is on fixed versus floating rates? If you had hedges in 2023, could this worsen when they roll off into 2024?
Yes. Thanks for the question. The key really to understand is the net financial income and expense, which will increase materially given the increase of the interest rates. You know, it's indeed partially mitigated by interest rate hedges. On average in 2023, we have around 60% of our net debt, which is hedged at fixed rates. However, the cost of the outstanding debt is expected to increase by around 2 % points year-over-year. You can see it's quite significant. This is the major impact. The tax rate increase has kind of a marginal impact compared to that. You know, of course, the hedges are coming to maturity, so when we roll them over, we are faced with the current condition of the market.
The majority of our debt is denominated in US dollar.
If I may continue with you, Sandrine, Kerry Holford from Berenberg. She goes on the margin outlook for 2023. Your full year 2023 guidance suggests 2023 margins could be below 2022. What scenario would drive this? She's coming back on the non-core assets, and I see that in the chat several times. Perhaps you could re-emphasize on the non-core assets. You reference selling non-core assets within your guidance comment. How much of this is baked into 2023 guidance, and which assets are now considered non-core?
Right. On the margin, I think it's, you know, largely also the effect of the top line. One of the key element which has an impact on the margin in 2023 is linked to the effect year-over-year of the LOE and also the inflation element. Even though we're gonna work on managing our costs, these are elements that we cannot fully absorb, and that the launches will not necessarily compensate for. I think that's going to be the key element of the drivers. Now, on the sale of the drug, as I said, we sold five drugs, which were commercialized in Europe.
Just to reiterate what I said on the impact, it's a very small lower sales impact because as of January, we will not continue to book the revenue that these drugs were generating in 2022, so very marginally low sales impact. The gain will be booked and have an impact on bottom line, but that's a small, again, a small positive impact, which is captured in the guidance that we've just given on the margin. You know, we have not defined what we call core and non-core in a way, but we get to these decisions when we see that within the established brand. And again, it's something I've looked...
We've done this, except last year, we've done this over the five or six previous year, regularly exiting some products, as the management of these drugs was becoming, you know, too cumbersome for the, for the return that they were generating. We do this when it's only, you know, making sense financially, looking at the expected value, the value creation versus the future cash of these drugs.
Okay, thank you. Simon Baker from Redburn has a question for Charles. Can you give us an update on your view on the dynamics and opportunity in the Myasthenia Gravis, category as the Dysport sales evolve? Yeah.
Perfect. Thank you. Thank you, Simon, for that question. What we see certainly with this market is one that is still very underserved, so large number of patients that are not, you know, well controlled. With the entrance, like the first entrant that has come in, there's been, of course, a broad awareness in the market of Myasthenia Gravis, and it's maybe activated a larger pool of patients to seek treatment. What we will bring in is really a choice for physicians and for patients, the preference that they would have for at home or in office administration.
We see with our combined portfolio of these two mechanisms of actions that have both been proven to be targeted for the underlying cause of the disease, that we can essentially manage the disease control for patients. What I would say over time, what we will see this market, of course, growing as a result of these targeted therapies now coming into the market. We will all benefit from that growth with especially the first three entrants, ourselves, argenx, and also Alexion. We see over time that this market will further disrupt and displace IVIG, and on the other end, also move earlier into the space of standard of care, which are really non-targeted therapies like steroids or immunosuppressants.
With this growth and expansion, we feel we will all benefit in the significant unmet need in this market.
Thank you. If I may, I'm transitioning exactly to a question from Charles Pitman-King from Barclays, on rozanolixizumab. Can you speak to the confidence that you have on whether MuSK patients will be included in the expected label? How have conversations been with the FDA? I think, Iris, this goes to you.
Of course. Thank you. I hope I have expressed the confidence that we have in our MuSK-positive data. Of course, this is the decision of the regulatory agencies, including FDA. I'm very confident, but again, have to declare that in the end, this will be a decision by the agency. If you look at our data, this is the largest database in MuSK-positive patients in the registration study and very convincing results. Thank you.
Thank you. I will continue with Charles' question to you, Sandrine, on margins. How much of the 2023 EBITDA margin expansion is expected to be driven by the Zogenix acquisition turning accretive? Can you speak to your confidence on delivering expanded margins despite investing in several product launches?
Yeah. Well, thanks for the question. We said that it would be earnings accretive, and language matters here, which means it's not margin accretive in 2023 for Zogenix, but we're very confident that at some point, you know, looking beyond that, it will really help midterm on the margin as Fintepla. Sorry, I'm not sure what was the second question.
The confidence in the delivering expanded margins despite investing in several product launches.
for.
Beyond Zogenix. It's now going more general.
In 23. Just checking.
In 2023. In 2023.
You know, here I think I've highlighted the underlying component of that, but you should have in mind also the effort that the entire company is doing on this transversal cost category management. In 2022, we benefited from already strong effort, but we are aiming to more than double the impact in 2023, and that's why we are in a position to reallocate this resource and support the growth and the preparation for the launch.
Stay tuned, Sandrine. Dominic Lunn from Credit Suisse is asking, you have reiterated 2025 targets over EUR 6 billion sales and low to mid 30% margins. What assumptions on European pricing and reforms are built into this midterm guidance? Consensus is on sales, but at the lower end on margin. Would it be fair to say the outlook in Europe now looks a bit tougher when you originally set this guidance? Is this offset by higher leverage on marketing and selling and R&D decreasing than previously expected?
We have not changed the overall, you know, 2025 guidance. I would say that, probably my colleagues are better positioned than I to comment on our view on the European pricing environment. We usually take into account, you know, in the various geographies, what we see depending on the positioning and the access that we have for our products that is reflected in our plan. Again, the key, the key expected growth of the margin in 2025 will largely be function of the top line evolution, the ramp-up of the new launch products.
I think, you know, we do expect to see an improvement, which is going to be more pronounced as we back and load it, expansion of the margin as we go towards 2025. I don't know, Charles or Emmanuel, if you want to comment on European pricing.
Charles?
Yeah. I'm happy to just make a very brief comment. Of course, pricing is in Europe generally is set at the time of launch and negotiated on a central level. There is not an annual price inflation that you would see typically, maybe if you compare that to the US market. The price that we have at launch is very much set. And then, of course, the volume and access we generate for patients with that price is what is the main focus, of course, in Europe.
Charles, the very last question as I have you. Peter Welford from Jefferies. What is the potential in terms of zilucoplan in additional indications? Is the aim to have them in other indications that roza is or other areas? Do you expect sales in all gMG patients day one, or will it be mainly MuSK? Do you have anticipate a significant price premium to IVIG in Myasthenia Gravis?
Yes.
If possible, a short answer.
Yeah, very quick on complement inhibition. Of course, this class has been well studied or this mechanism of action. We do see other patient populations in zilucoplan. When we are ready with those, we of course will disclose them to you, but we see more potential there. When it comes to the MuSK patients, of course, as we mentioned in our label, that might be an obvious first area to go for rozanolixizumab, but we see the broad indications we will have across acetylcholine receptor positive and MuSK patients. Our positioning will be broad and we wanna capture, you know, the full share of that market. Hopefully that's answering the question for your answer.
Thank you. I know you know where to find us for all your other questions. We have kept your questions, and we will get back to the individual analyst with a full answer. Sorry if we couldn't do everything, but I'm cognizant of the time. Thank you so much for listening in. Thanks for presenting. Have a good day. Thank you. Bye-bye.