We need to see that. We simply don’t know. Equally for Symbicort, Symbicort it’s quite amazing that after 20 — more than 20 years of initial launch, that Symbicort is still annualizing more than $2 billion a year. Very fast growth again in the emerging markets, but also equally this year so far in the United States. And it’s heavily driven by the fact that we have an authorized generic available as well as we have also lowered our WAC, the so-called list price, in the United States. So it becomes more affordable for many patients. And once again, whether that will continue during the course of the year needs to be seen. But so far, it’s very pleasing to see that both brands are off of a very strong start in the United States as well as outside of the United States.
Pascal Soriot: Thanks, Ruud. Maybe I would add that everybody talks about one-offs. And to be honest, I’m not sure why there’s such a focus on one-offs. If you look at Farxiga in the U.S., Q4 sales were $450 million, Q1 sales are $470 million. And if you look at the trend over the last few quarters, we’ve had a very strong trend. And if you may be combine this with the prescription trend that Ruud was talking about, they sell a little bit of stock up. But it is not really what drives the trend for Farxiga, it’s a very strong trend, not only in the U.S. but across the world. So every country is behaving the same way. We have very strong uptake in kidney disease, heart disease, diabetes, et cetera. The next one is Steve Scala at Cowen. Over to you, Steve.
Steve Scala: Thank you so much. I have two questions. First, DBO6 hit its primary completion in March. Is the data in-house? And is that underpinning your confidence? And second, why is there, what seems to be a long delay in presenting the oral GLP-1 and oral PCSK9 data? I could think of four possible reasons. One, there’s a lack of appropriate venues. Two, AstraZeneca is strategizing on next steps on how to approach the market and wants to figure this out first. Three, there’s some issue with the molecules or data that you’re working through, perhaps it is underwhelming. Or four, we’re just being too optimistic on how long this all takes. So any thoughts would be appreciated? Thank you.
Pascal Soriot: Thanks, Steve. So let me just address the last one quickly, and then we could talk about DB06. And you forgot one option which is our policy, and our policy is to present data at medical congresses and that’s what we have decided to do, we stick to this. But maybe your second option is also part of it. For sure, we are, in the meantime, strategizing what we’re going to do with our portfolio and how we develop this product. But really, the driving force is simply we debated it internally because you raised a good point, but we concluded we didn’t want to do — to come up with an exception here. And so you’ll have to wait for the next potential option as a medical congress. We are, by the way, I have said, and I think I can confirm, we’re starting Phase 2 this year. So we are on track, and we will not be preparing Phase 2 if we were not confident with the oral group 1. DB06, Susan, do you want to cover that?
Susan Galbraith: Yes, sure. So DESTINY-Breast06 is obviously a setting earlier than DESTINY-Breast04. It includes the IHC 1+ and 2+ as well as a group of the ultra-low group. And the confidence in DESTINY-Breast06 is really built from the DESTINY-Breast04 dataset, which we obviously presented some time ago. So we are looking forward to the data. We said its first half of this year. So hopefully, you don’t have to wait too long for getting those data, and we’re eager to share them with you. Again, just as a reminder, the primary endpoint is PFS in the HER2 low group. So that the IHC 1+ and 2+, and then there’ll be descriptive analysis of the HER2 ultra-low patient population as well. And as a reminder, further, even though these patients are below the 1+ category, they still have a higher number of HER2 receptors on the cell surface than normal epithelium.
So just to put numbers on that. Normal epithelium for HER2 is about 20,000 receptors per cell. At the 1+ – to 2+ ranges between 100,000 and 200,000. So in that ultra-low group, you’ve got somewhere between 20,000 and 100,000 receptors per cell. So you can see that there’s probably a significant proportion of that group that will have higher expression level of HER2 on the cell surface than normal epithelium would. And that’s one of the reasons why we think there’s a potential to go beyond the 1+ group into that ultra-low group and see benefit over the current standard-of-care chemotherapies.
Pascal Soriot: Thanks, Susan. Next question is from Simon Baker of Redburn. Over to you, Simon.
Simon Baker: Thanks Pascal for taking my questions. Two, if I may, please. Firstly, going back to Farxiga. I just wonder if you could talk us through the rationale for the timing of the authorized generic now. I may be missing something, but the [indiscernible] pattern goes in October ’25. So some thoughts there would be helpful. Alongside also the FDA issuing a request for pediatric studies in March 2019, that hasn’t yet been reflected in the orange book. So I just wondered what the state of that was. And then secondly, on TROPION-Lung10, you’ve moved forward with one of the combinations, which is in the TROPION-Lung04 study, obviously, on high confidence. I just wondered where that — where your confidence rests with the combination with volrustomig and sabestomig? Thanks so much.
Pascal Soriot: Thank you, Simon. So Ruud, in the past, you were complaining not enough questions to BioPharma. You’re now going to complain too many questions.
Ruud Dobber: No, it could be less. But no, it’s a great question, Simon. So why now, it’s relatively straightforward. First of all, we have a huge opportunity still in CKD and heart failure. And it is clear from all the analytics we have done that a lower cost option for some of those patients are very important in order to capture even more volume. The second one is also true, to that extent, it also mitigates the impact of a potential MCAP. So the inflation penalty in the United States as well. So those two factors were important regarding the timing. Regarding the pediatric indication, it’s not yet in the orange book, so that’s a very good observation. But equally, we feel comfortable that the FDA will grant us the pediatric indication. And hence, our base assumption is still that the patterns will stay in place till April 2026, which we have signaled multiple times.
Pascal Soriot: Thanks, Ruud. Susan, do you want to cover the second question?
Susan Galbraith: Yes. In the TROPION-Lung10 study, as I mentioned before, is the combination with volrustomig and Dato and it’s in a patient population that’s greater than 50%. As we said before, what we see in terms of the evolution of the IO checkpoint inhibitor landscape is a segmentation. And our two bispecifics, we see the volrustomig PD-1 TIGIT as being focused on the IO sensitive or highly expressing PD-L1 part of the population, and that’s in line with what you see in terms of the patient population in TROPION-Lung10. Volrustomig, we’re focusing that on the tumor types where CTLA-4 sensitivity has been demonstrated and can add extra efficacy. Obviously, with volrustomig, it is designed to be better tolerated than the combination of CTLA-4 and PD-1 separately, because it only binds CTLA-4 in the presence of PD-1.
And we have shown an improved safety profile, but it still does have more side effects than you get with a PD-1 agent on its own or with volrustomig. So we will select that drug where it will make the biggest difference. And you’ll see that as the — as you see the evolution of the EVOLVE studies with volrustomig.
Pascal Soriot: Thanks, Susan. Next question is from Andrew Berens at Leerink. Over to you, Andrew.
Andrew Berens: Thanks. And congrats on the strong quarter. Kind of a big picture question on the AKT class given the results of Truqap. Just wondering how you see it integrating in the evolving paradigms. It’s obviously incredibly dynamic. And specifically, would like to know how you guys see the AKT class integrating with CDK2 agents, CDK4 selective drugs, the oral SERD to graders, and also the ADCs that are starting to spread their wings into a number of these areas?
Pascal Soriot: Okay, Andrew, thank you. Thank you for asking one question. Actually, Susan, over to you?
Susan Galbraith: Yes. So thanks for the question. So AKT is obviously part of the PI3 kinase AKT pathway, which is the most commonly mutated or aberrant pathway in cancer. So we think this is a very important mechanism. And we are looking at combinations of capivasertib with our camizestrant, our oral SERD drug that’s already in multiple Phase 3 trials as well. So I think there’s potential for it to be further expanded beyond the current set of trials that we’ve already got in development. And I do think there are data that it can be a potential combination agent with a number of the other things that you raised. We do have a CDK2 inhibitor, a highly selective CDK2 inhibitor, which we profiled at the AACR meeting that was in San Diego earlier this month.
We think that’s a very exciting molecule that will address the resistance mechanisms to the CDK4/6 inhibitors. And so I do think that this cost of agents can be combined with the emerging both new endocrine backbone agents and the newer versions of things to address the CDK4 mechanism and the resistance to CDK4, which typically is represented by sensitivity to CDK2 inhibition.
David Fredrickson: Just maybe to also build on to Susan’s answer, and I think what’s important and great about this is we’re talking about leadership in breast cancer. And as part of that leadership in breast cancer, we’re really looking to build and improve upon the two existing pillars in the treatment of metastatic disease and then adding a third. And the existing treatments and existing pillars are ET plus or minus CDK4/6, and then obviously chemotherapy. I think what’s important about the AKT class is it gives an opportunity for patients to continue to stay on ET-based therapies, which has a lot of benefits associated with it. We also know, though, that at some point, ET therapies are no longer effective and that it’s a time to start to switch towards chemotherapy.
And within that, that’s where the ADCs now create a third new pillar that sits in between classical chemotherapy and ET-based approaches. We hope that DB06 will provide even a further therapy option that sits within this. But you start to see the opportunity to begin to offer to physicians more options for how they can think about treating their patients as the disease progresses. And we’ve got best-in-class therapies to go into each of those pillars and then gives us an opportunity to look at combinations down the road.
Pascal Soriot: Thanks, Dave. Actually, this discussion gives me chance to go back to, I think, the question Richard asked earlier about the pipeline. I mentioned combinations, but also this pipeline enables us to actually shape the treatment algorithm, as Dave was suggesting a minute ago, in breast cancer or lung cancer. And it also enables us to better partner with lung cancer oncologists or breast cancer oncologists and really truly be part of the way breast or lung cancer or other cancers are treated. And it’s true for cardiologists, not only managing cardiovascular risk, but also if you look at amyloidosis, we have 2220, which is an amyloid depleter, we also have a [indiscernible]. So Again, all of those things will give us a great chance to partner with key physicians, but also leverage our portfolio to shape treatment algorithms and look at combinations. Emily Field of Barclays. Emily, over to you.
Emily Field: Hi, thanks for taking my questions. Just two on respiratory. A lot of excitement about the tezepelumab COPD data to be presented at ATS. Given what we’ve seen so far, is it your expectation that this would be taken in late-stage development in a broader eosinophil population, i.e., over 150s and over 300s? And then on the back of that, similar to the obesity question that was asked earlier. You have so many assets in late-stage development in COPD. Maybe asking from our side, what should we be focusing on in terms of just all of the late-stage COPD programs that you have? Thank you.
Sharon Barr: Sure. Thanks so much for the question. So I’ll start with your first one which is about tezepelumab in our Phase 2 core study, and then I will speak more broadly about this COPD portfolio. So you touched on teze in our recent Phase 2 trial completion, and we look forward to presenting those data at ATS in the very near future. As I’m sure you know, teze is a monoclonal antibody directed against T-slip. It is the only biologic approved first here severe asthma with no phenotype, and we see tremendous potential for this molecule in COPD. The course Phase 2 study was specifically designed to look at a broader population of patients. So it included patients irrespective of inflammatory drivers, eosinophil levels, emphysema, chronic bronchitis and smoking status, while other trials were more limited.
And this included a prespecified subgroup analysis in populations with different eosinophilic levels, so including below 150, above 150 and above 300. We will present the data that we fully analyzed at the upcoming ATS meeting. But I will only venture to say that we are excited about the possibility of teze in a broader population. It is worth noting that other molecules in this class are playing in the high eosinophilic levels, at more than 300 eosinophils per microliter. And that’s only about 35% of the population that’s eligible for biologics. But those above 150 eosinophils per microliter are about 65% of the biologics eligible population in COPD. So we think that’s a really important differentiator for this molecule. Now you also mentioned — I think you also asked us about our plans to go forward together with our collaborators at Amgen.
We are actively planning the next stage of development. You asked about our overall portfolio in COPD. And I think it’s worth mentioning here that COPD is a very heterogeneous disease with multiple drivers. And to that end, we think that there are multiple mechanisms that may have substantial clinical benefit. So we are testing multiple mechanisms, and we are testing them in populations that allow us to differentiate them from each other. Tozorakimab, as we have previously described, is a differentiated IL-33 monoclonal antibody because it can bind and block both ST2 and RAGEEGFR signaling. We think that’s really important in this disease because it not only blocks the inflammatory pathways, but it can also block mucus production and epithelial remodeling through RAGE EGFR.
So we view that as a differentiated mechanism, which we think may also have very broad utility in the COPD population. So early days, we are reading into our Phase 2 data and thinking about our Phase 3 plans going forward, but I think that we have the potential to be really paradigm shifting for people living with COPD?
Pascal Soriot: Thank you, Sharon. Luisa Hector at Berenberg. Luisa?
Luisa Hector: Hi, thanks, Pascal. Perhaps I could touch on capital allocation. So your high burden of deal-related payments will start to ease at the end of this year, so that improves your cash flow outlook. So will this lead to a change in the nature of deals which you can do? And perhaps you could remind us of your dividend policy given a slightly unusual announcement of the 2024 dividend recently? Thank you.
Pascal Soriot: Thanks, Luisa. Aradhana, your favorite question.
Aradhana Sarin: Thank you, Luisa. So our capital allocation priorities remain unchanged. As you’ve seen, we’ve been very active on the BD front, but we also now sort of need to create value actually from the acquisitions and the partnership transactions we’ve done. So we need to focus on execution of those transactions. We did announce a 7% dividend increase in line with our progressive dividend policy, but also recall that we did not increase dividends in 2022. And so the Board takes a decision on when and how they can increase dividend based on our overall capital allocation priorities. But the capital allocation remains unchanged.
Pascal Soriot: Thank you, Aradhana. So thank you very much for all your great questions. I think it is time for us to respect your time and close this call. Again, thank you so much for all your great questions and your interest in AstraZeneca, and have a good rest of the day.
