Ladies and gentlemen, welcome to Roche Virtual Event Update following Angiogenesis 2023. My name is Henrik, and I'm the technical operator for today's call. Kindly note that the webinar is being recorded. I would like to inform you that all participants are in listen-only mode during the call. After the presentation, there will be a question and answer session. You're invited to send in questions for this throughout the entire session using the Q&A functionality of Zoom. In addition to that, you may also raise your virtual hand to address your questions verbally. For participants joining via phone, to raise your hand, use star nine on your phone's dial pad. When you then get selected to ask your questions, please follow the instructions from the phone and press star six to unmute yourself.
One last remark, if you would like to follow the presented slides on your end as well, please feel free to go to roche.com/investors to download the presentation. At this time, it's my pleasure to introduce you to Bruno Eschli, Head of Investor Relations. Bruno, the stage is yours.
Thanks, Henrik, could I have the first slide, please? Welcome to our first IR call in 2023, focusing on our fast-growing ophthalmology franchise, and let me quickly guide you through today's agenda. We have three speakers with us today. The first one will be Nilesh Mehta, our Global Franchise Head of Ophthalmology, responsible for global product strategy. Nilesh will provide an update on our overall franchise strategy. Secondly, we have Christopher Brittain, our Vice President and Global Head of Ophthalmology, responsible for product development. Chris will provide an update on our early and late-stage ophthalmology pipeline, including latest platform technologies added, such as, for example, our cell-based therapies or the development of digital tools. Finally, we are very pleased here to have with us today Dr.
Veeral Sheth, a well-known retina specialist and a Vabysmo clinical investigator who will lead us through all the 3 pivotal studies presented in angiogenesis. The studies are, firstly, the phase III study, BALATON and COMINO for Vabysmo in RVO. Secondly, the phase III study, Pagoda for Susvimo in DME. Thirdly, the phase III study, Pavilion for Susvimo in diabetic retinopathy. Overall, the call will go for 90 minutes. We will have 45 minutes planned for the presentations, and this will be followed by 45 minutes to take your Q&A. During the Q&A, we will also be joined by Yu Lin, our lifecycle leader for Vabysmo, and by Pierre-André Delay, our lifecycle leader for Susvimo. Could I have the next slide, please?
Before we start with the presentations, I just wanted to make a quick upfront comment on what an exciting year actually lays behind us. Last year, at around the same time and the same place, I showed a slide citing various polls amongst ophthalmologists. Firstly, on the high unmet need still remaining for patients with AMD and DME. Secondly, on the ophthalmologist's willingness to switch their patients to Vabysmo or to consider Vabysmo as an initial therapy based on the pivotal phase III data which we had presented. Today, one year later and four quarters into the launch, and with additional real-world data being collected and confirming Vabysmo's differentiated efficacy and safety profile, we clearly see these changes in the paradigm of treatment now happening.
As you can see on the left side, Vabysmo has achieved an excellent market uptake, also when compared to historic launches like, for example, Lucentis or EYLEA. Actually, the identical graph we could show for the U.S., and what you also can see here clearly is the accelerated momentum which we had last quarter after we got the J code in October. As mentioned before, we see roughly 70% of the patients being switchers from Eylea. 50%-20% of the switchers coming from Lucentis. Amongst the remaining part, we see an increasing number of newly diagnosed patients. On the right side of the slide, you see a 2017 and 2022 sales splits according to our main business areas.
The graph show recent development successes, especially for our drugs like Ocrevus, Evrysdi, Enspryng, and Hemlibra, which have allowed us to successfully enter new markets and have led to a diversification of our pharma portfolio outside of oncology. Only within the last five years, Roche emerged as an industry leader in neuroscience and hemophilia A. Going forward, we actually expect that this broadening will continue by also becoming a leader in ophthalmology. With that, let me hand over to Nilesh for an update on our ophthalmology franchise. Nilesh, please.
Thank you so much, Bruno. Good morning and good afternoon, everybody. It's a great pleasure to virtually connect with many of you again and provide an overview of progress within Roche Ophthalmology. Next slide, please. You know, 2022 was a year of significant progress. This is the fruition of efforts made over many years. Last year, Roche made progress with launches, additional positive phase III data, both in longer term follow-up with approved indications in neovascular AMD and DME, as well as new indications, as just highlighted by Bruno. We progressed the pipeline. You'll hear later from Chris and Viral on the data that was just presented at the Angiogenesis conference.
I like to think of this being a pivotal year where the franchise made the transition from phase III potential, which we've been discussing with you over years, to patient reality. If we move to the next slide. This is not news to many of you. Retina continues to be the largest value segment within the ophthalmology market. It's continued to forecast to grow even further, driven by EPI, the growing populations of aged people around the world, as well as diabetes. In addition to that, we think it's gonna grow through innovation, addressing unmet need. Next slide. Let's maybe look at how we frame the unmet need in retina. You know, we see patient outcomes compromised by discontinuation, undertreatment, and efficacy beyond anti-VEGF. Let's go into each of those.
You know, a third of patients discontinue on any treatment in spite of the benefits they see in vision when they're treated. In the real world, the ability for healthcare systems and providers to deliver sufficient doses that sustain outcomes is simply not possible, in many circumstances. Also, we know that even in a phase III setting where patients are treated and followed up robustly, only about half get to 20/40 vision, which is about 70 letters, usually that required for driving. Hence our approach has been to innovate beyond anti-VEGF alone and address the multifactorial disease processes that occur and that can then deliver durability with sustained outcomes. Next slide, please. That kind of nicely segues me into the Vabysmo phase III, two-year follow-up data that really confirmed and augmented the one year.
You know, in the matched dosing arms, if you see on the left-hand side of this slide, in DME, Vabysmo showed greater drying than the comparator, Aflibercept. In previous studies where additional anti-VEGF has been used, we haven't seen such an effect. Durability increasing to over 60% of patients achieving Q16 every 4 months in both neovascular AMD and consistently in DME, and 80% achieving Q12 dosing every 3 months or more. These are the data from the phase III study. Let's take a look at what we know is happening in the clinical practice setting. We move to the next slide. I think this is, you know, the evidence is that really Vabysmo is working very well and is very consistent with the phase III studies.
What we're particularly pleased is that in such a short period of time, we're able to share clinical practice data after the pivotal phase III data. As you could, as you would expect, most of the initial use is coming from switch patients whom doctors believe to have persistent fluids and where outcomes could be improved. About two-thirds of this coming from aflibercept. What we're seeing is that they're noticing positive anatomic impact across a number of markers, including central subfield thickness, intra and subretinal fluid. Along the way, this data is really confirming the safety profile in clinical practice, and this continues to build confidence in greater first-line use for Vabysmo. Moving to the next slide.
The result of both the Phase III data and this real-world clinical practice data is a really encouraging and positive launch for Vabysmo. Vabysmo had a very encouraging quarter four, and we're seeing continued growth in the new year, proving that our sales in Q4 were not a blip, and we're looking forward to sharing further updates as we move through the year. I'd like to highlight that healthcare systems also see the value of Vabysmo. This is demonstrated with over 50 approvals in a number of countries, and as well, a number of national reimbursements in a really relatively short period of time, just over 11 months since the first U.S. approval.
That and the reassurance of the safety profile with over 450,000 vials, and this number continues to grow on a daily basis, is continuing to drive further first line use and expansion into that space. You'll hear more about broadening the additional indications. Retinal vein occlusion is the third biggest unmet need in retina. The uptake and the real-world experience continue to provide confidence to us that Vabysmo is positioned to be the new IVT standard of care in retina. Next slide. Let's take a look at beyond IVT delivery. I want to, on this call, reassure you of our commitment to the Port Delivery System platform and Susvimo. It's the only type of device of its kind in the world.
We took a difficult but, I think, responsible decision to voluntarily recall Susvimo based on some manufacturing variability that we uncovered. This is a technical challenge to overcome, and the teams have already made significant progress to understand it better, and we look forward to kind of bringing this platform back to the market in about a year. I want to reiterate the commitment to the platform. It has the potential to provide continuously medicine to the retinal tissues which require it and in a manner that no other alternatives are unable to, and thereby deliver on the promise of outcome certainty. The recent data from the phase III Pagoda and Pavilion studies, which we'll hear more about, as well as some of the pipeline molecules destined for the PDS, only further reinforce our commitment to its part in addressing unmet need in retina.
Hope that gives you a good overview. With that, I'd like to hand over to my colleague, Chris Brittain.
Thanks, Nilesh. As you've seen, patient uptake of Vabysmo is going from strength to strength. In fact, we're now seeing in the pipelines of other comanies that Faricimab is being used as a comparator in their randomized controlled trials, reinforcing our belief that Vabysmo is the new standard of care. Now I wanted to share a deeper dive into what's come out in our pipeline. If we can go to the first slide, please. With the platform that Vabysmo and Susvimo have given us, our research engines are taking a two-pronged approach to alter the trajectory of vision loss experienced by so many people across the world. If you consider that anatomical damage generally precedes functional loss, and that the end game for many of these conditions is functional blindness.
We're aiming to firstly address this area at the top left of the graph to preserve vision in early-stage disease. A great example of this is the Pavilion data, which Veeral will be sharing with us later. Secondly, to restore functional vision to those suffering from end-stage disease in the bottom right of this graph. The great example we have here is through our OpRegen cell therapy program in geographic atrophy, which is in clinic. Additional early research work in the area of optogenetics. If we go to the next slide. We aim to achieve this strategy through these three linked approaches. Firstly, identification of biomarkers and their integration with patient monitoring and clinical decision support to help identify the right treatment for the right patient. Secondly, through new mechanisms and action and new indications.
Sorry. Having demonstrated that benefits of dual pathway inhibition with Vabysmo, we've now started 2 phase III studies specifically addressing inflammation with our IL-6 program. Many of these novel MOAs that we have in our pipeline will open up the potential for combination therapy in diseases such as geographic atrophy, diabetic macular edema, which we all well recognize to be multifactorial. Finally, we continue to investigate additional extended durability approaches in addition to the Port Delivery technology and novel approaches such as cell therapy and gene therapy. A recent example of which was the gene therapy was the deal with the gene therapy company, Avista. Next slide. This leads us to the current state of play of our pipeline.
On top of Vabysmo and Susvimo, we have 9 additional new molecular entities in clinic, which 1 is in phase III, and that's the IL-6 program. 3 are in phase II, 1 of which is the vicasinabin molecule, which is again, in the top left of that graph, which is in patients with diabetic retinopathy, and 5 molecules in phase I. We believe that this represents the strongest pipeline in ophthalmology. Within this, we expect, as I say, this phase II vicasinabin diabetic retinopathy study to read out in the second half of this year. Next slide. I want to take a little bit of a more detailed look at the IL-6 program.
It's just important to know that IL-6, and remind everybody, that IL-6 is a truly pleiotropic cytokine and is involved in many pathways, including angiogenesis, blood retinal barrier breakdown, leukocyte adhesion and chemotaxis, and of course, inflammation. IL-6, as you can see on the right here, has also been shown to be upregulated in multiple retinal diseases, including diabetic retinopathy, vein occlusion, and retinal detachment. Next slide. Our anti-IL-6 mab molecule binds IL-6 and has a modified Fc region which enables rapid systemic clearance, important for our ophthalmic products. While the impact on patients of DME remains well-recognized, and we have 2 phase II studies ongoing in this disease with anti-IL-6, we are pursuing a fast to market strategy in the uveitic macular edema indication due to the high unmet need in this indication.
UME is the accumulation of fluid in the retina that occurs as a complication of uveitis in about a third of uveitic patients. As a rough idea, there are approximately three-quarters of a million patients who have uveitis in the E.U. and U.S.A. alone. Moving on to the next slide. You will recall that we've mentioned the DutaFab platform repeatedly over the years. As a reminder, these are the next generation of intraocular bispecifics. They're the size of a Fab fragment similar to ranibizumab, but with the ability to target multiple moieties. They can be highly concentrated, are engineered for higher affinity, and are extremely stable, meaning that they are also compatible with a Port Delivery System implant. In fact, they're all going to be primed for entry into this device.
I'm really excited to say, though, that 3 DutaFabs are actually in clinic in phase I, with the most advanced being the VEGF Ang-2 program. Next slide. I now want to switch over to geographic atrophy. As we all know, February is a big month with the potential first approval of any therapy for patients with GA. What's very clear is that even if any therapy is approved this year, a lot of unmet need will remain for the over 5 million GA patients globally, both in terms of efficacy, durability of treatment, and patient convenience. This is because GA is a complex multifactorial disease, and complement is only one part of the story. Next slide. Our approach to GA involves 2 programs.
Firstly, targeting complement factor B systemically with an antisense oligonucleotide to inhibit complement factor B production, and thus reduce the activity of the alternative complement pathway. This systemic and subcutaneous approach has the potential upside of treating both eyes simultaneously and potentially being self-administered, thus allowing much greater and more convenient care for the patient. Next slide. Secondly, OpRegen is an allogeneic RPE cell replacement therapy that is in phase II presently, looking at both restoration of RPE loss in areas of GA and also optimization of the surgical procedure used to safely and effectively deliver the cells subretinally. As presented last year, the phase I did show restoration of retinal structure in some patients on top of gains in visual acuity. We're excited for the continuation of the OpRegen program. Next slide.
In closing, I'm excited also to share that our Personalized Healthcare program continues to go from strength to strength, with both development of algorithms to improve personalized patient management and also the release of the next version of the Home Vision Monitor in the second half of this year. For those of you who don't know, this device has already demonstrated significant success during COVID and actually won the U.K. Health Services Journal Award in 2022 for the Virtual Care Initiative of the Year, which was formed in partnership with Moorfields Eye Hospital. This is a great example of the collaborative approach we take with so many partners in the development of our therapeutic pipeline. With that, I'm very happy to introduce Dr.
Veeral Sheth, medical retina specialist and Partner and Director of Clinical Research at the University of Retina and Macular Associates, Chicago, to talk about the latest Susvimo and Vabysmo data. Over to you, Viral.
Thank you, Chris. As Chris mentioned, my name is Veeral Sheth. I'm a retina specialist in the Chicagoland area, I was a principal investigator on all the studies that we'll be discussing today. Next slide, please. Here are my financial disclosures. We can go ahead to the next slide. As Bruno mentioned earlier, as Chris just mentioned, we're gonna be talking about 3 specific clinical trials. One, looking at faricimab, in this case, a phase III study looking at the treatment of retinal vein occlusion. We'll pivot to 2 Port Delivery System clinical trials in phase II that were just presented as far as data goes at Angiogenesis this past weekend. We'll go over a little bit of that data as well. Let's go to the next slide.
First, we're looking at Faricimab in retinal vein occlusion. These are results from the BALATON and COMINO phase III studies. BALATON was a clinical trial looking at branch retinal vein occlusion, whereas COMINO was looking at central retinal vein occlusion. Let's go ahead to the next slide. These were phase III randomized, double masked, multi-center trials designed to evaluate the efficacy and safety of Faricimab versus aflibercept. You can see the key inclusion criteria here. And of note, the primary endpoint in both of these studies was the change from baseline in BCVA at week 24. Patients were randomized into one of 2 groups, one receiving Faricimab every 4 weeks and the other receiving aflibercept every 4 weeks. This was going through week 24.
That's where the primary endpoint is, and that's really the data that we're gonna focus on today. Interestingly, this trial is set up at week 24 to transition patients to Faricimab into a personalized treat and extend regimen. In other words, these patients were converted all over to Faricimab, and their dosing interval could have been extended, and we're looking forward to seeing what that data shows once that study wraps up. We'll go to the next slide and really just focus on the 24 week data. We saw that Faricimab achieved robust vision gains and reductions in CST across the studies, and that the results were comparable between treatment arms in both trials.
First looking at the top here, this is the BALATON data where we saw 16.9 letters gained in the Faricimab Group versus 17.5 in the Aflibercept Group. As far as central thickness of the OCT goes, we saw 311 micron improvement in the Faricimab Group versus 304 in the aflibercept group. Similar trends in the CAMINO study as well, where we saw 16.9 letters gained in the Faricimab Group at 24 weeks versus 17.3 in the aflibercept. Again, nice CST results as well, 461 microns of improvement in the Faricimab Group vArsus 448.8 in the Aflibercept Group. The next slide, please.
This next slide is really kind of where, as a, as a clinician, as someone that was involved in these studies, but more importantly, as someone that treats patients in the office, this is where I, you know, I really focus on. For us, Faricimab represents, you know, a new mechanism of action. What we wanna see in these newer therapies, is anatomically, are we seeing significant differences? Here what we saw was that more patients achieved absence of macular leakage with Faricimab versus Aflibercept at that 24-week endpoint. If you look at the left here, BALATON, we saw 33.6% of patients receiving Faricimab achieving that absence of macular leakage versus 21% in the Aflibercept Group.
In COMINO, we saw the same trend, 44.4% in the Faricimab Group achieving absence of macular leakage versus 30% in the Aflibercept Group. Again, this is kind of to me where we wanna see that progress, and I think this is translating to better patient outcomes. Let's go ahead to the next slide. Faricimab was well tolerated with a safety profile similar to that of Aflibercept. Again, it was mentioned earlier, the TRUCKEE study. The TRUCKEE study is a real-world study that we looked at. Again, we're one of the investigator sites for that study. And what we're seeing in these real-world datasets is good, not just efficacy, but safety. In today's environment, this is paramount.
Again, fortunate to see in this Phase III study, similar trends, and again, a nice safety profile for Faricimab. Let's go to the next slide, please. From there, we're gonna pivot again from Faricimab to Port Delivery System. We had two really nice presentations on Saturday. This first was looking at Port Delivery System with ranibizumab in patients with diabetic macular edema. This is the primary analysis results of the Phase III PAGODA trial, presented just a few days ago by Arshad Khanani. Let's go to the next slide. PAGODA was a Phase III study designed to evaluate efficacy, safety, and pharmacokinetics of PDS Q24 weeks for diabetic macular edema.
Here you can see the study schema where patients were randomized into 1 of 2 groups, the first being the patients that received PDS implantation, just after receiving 4 loading doses of ranibizumab. At week 16 of the trial, they were able to get their PDS implant, versus the other arm. The second arm is the intravitreal ranibizumab 0.5 mg Q4 weeks. Again, about a monthly injection schedule up through that primary endpoint, which was at 64 weeks. What the primary endpoint was looking at was non-inferiority of PDS at Q24 weeks compared with monthly intravitreal ranibizumab 0.5 milligram injections based on the change in BCVA score from baseline averaged over weeks 60 and 64. Let's go ahead and look at the data. Next slide.
We saw that PDS Q24 weeks result in vision gains and CST reduction that were comparable to monthly ranibizumab through week 64. If you look on the left here, the vision changes, so BCVA changed from baseline again. We see at 16 weeks a little dip in the PDS group, which is very much what we would expect, just given the postoperative vision changes. That line matches back right up after a few weeks after the postoperative period. We saw in the PDS group 9.9 letters of vision gained at the 64-week endpoint versus 9.3 letters in the monthly intravitreal injection group.
From a CST standpoint, on the right we see that the patients that received the PDS demonstrated a 203 micron reduction in CST thickness versus a 199 micron reduction in the monthly injection group. Let's go ahead to the next slide. We see that with PDS Q24 weeks, we saw clinically meaningful DRSS improvements over time. This is looking at diabetic retinopathy scores. We saw a PDS group showing 39% in that greater than or equal to 2-step reduction in DRSS versus 41.9% in the monthly injection group. Let's go ahead to the next slide.
This is another kind of for us as clinicians, really, where what we want to see play out in the real world as well, which is 95% of the PDS Q24 week patients did not need supplemental treatment through each of the refill exchange intervals. Over on the right you can see what might have triggered a supplemental therapy. It's either a vision change or a CST OCT thickness change or a combination of those things that would have triggered a supplemental therapy. Really nice to see not greater than 95% of these patients did not need supplemental therapy. Let's go to the next slide. The ocular adverse events of special interest were well understood and manageable.
No cases of endophthalmitis or retinal detachment were reported in the PDS Q24 week arm. This is after implantation through week 64. Just, you know, I think that this is just demonstrating what we've learned over the life cycle of PDS clinical trials. I think surgically we're seeing better results. Here, you know, again, very reassuring, no cases of endophthalmitis or retinal detachment. Let's go to the next slide. This is the final PDS study that was presented a couple days ago. This is looking at PDS with ranibizumab in patients with diabetic retinopathy. A little bit of a different indication than Pagoda, where we were looking at diabetic macular edema. Here in Pavilion, we're looking at diabetic retinopathy. This was the primary analysis results of the phase III Pavilion trial presented by Dr.
Pieramici. Let's go to the next slide. Because this is a little bit of a different indication than Pagoda, I think it's worth taking a minute to discuss diabetic retinopathy in general in the context, especially, you know, coming from a clinician that sees this unfortunately too often in the office. We seeI that diabetic retinopathy affects over one-third of patients with diabetes and is a leading cause of vision loss in adults worldwide. We know that patients with moderately severe or severe NPDR are at high risk of progression to PDR and vision loss, PDR being proliferative diabetic retinopathy. This is really one of the endpoints we try to avoid in all of our patients with diabetes. Current diabetic retinopathy treatment guidelines generally recommend treatment upon onset of proliferative diabetic retinopathy or diabetic macular edema.
In other words, today's day and age, we're really only treating patients when they achieve that severe disease, proliferative diabetic retinopathy, or diabetic macular edema. Observation with no treatment is currently a common practice for diabetic retinopathy, given the treatment burden. Really, if we look at these bar graphs, on the right here, the ones that are most clinically relevant to me are when we look at that moderately severe NPDR group and that severe NPDR group. We see in that moderately severe NPDR group, 26% in one year can progress to proliferative diabetic retinopathy. If you're looking at the severe group, it's twice that, about 52%, progressing to proliferative diabetic retinopathy.
That's really where we get into trouble with our patients losing vision from vitreous hemorrhage or diabetic macular edema and, again, an endpoint that we would like to avoid if we can. Because of practical implications, treatment burden, and things of that nature, oftentimes don't treat these patients before they get to that point. Again, an unmet need for treatment options that prevent the progression of NPDR to PDR and development of vision-threatening complications, including DME. With that context in mind, let's go ahead and look at the study here. Let's go to the next slide. Again, Pavilion was a phase III trial, designed to evaluate efficacy, safety, and pharmacokinetics of PDS q 36 weeks for diabetic retinopathy.
If that 36 weeks looks different, it is because this is the first PDS study we are looking at with that 36-week interval. All the prior studies we've discussed in phase III have been Q24 weeks, just like the Pagoda study. Here are the two treatment arms that we see patients randomized to, the first being the patients that received PDS implantation. This is a patient group that received two loading doses, four weeks apart of ranibizumab, then within two weeks of that second loading dose, received their PDS implant. Versus the control group, the control arm here was a group that was clinically monitored. They did not start on therapy, could have received supplemental treatment along the way if they hit certain parameters. We'll talk about that in a moment here.
The primary endpoint on this study was superior efficacy of PDS q36 weeks compared with control based on proportion of patients with greater than or equal to 2-step improvement from baseline on the DRSS scores at week 52. Let's go to that next slide. All right, here's the data. A greater proportion of patients achieved that greater than or equal to 2-step improvement on the ETDRS DRSS, and retinal anatomy was maintained through week 52. On the left here, we're looking at that greater than or equal to 2-step improvement, and what we saw was patients that received the PDS, 80.1% of them at week 52 achieved that greater than or equal to 2-step improvement in DRSS score versus only 9% of the control group.
When we look at central retinal thickness, now again, we have to put this into different context than our Pagoda trial, which was looking at DME. Here we had patients that entered the study that could not have diabetic macular edema. In other words, their beginning CSTs were pretty good to start with. Even there, we see a trend towards improvement in the PDS group versus the control group, which we don't see much change at all in their central thickness. Again, just stability in anatomy after PDS implantation. Let's go to the next slide. Again, this is what I kind of keyed in on before we dove into the data, which is we want fewer and fewer patients over time to develop vision-threatening complications such as vitreous hemorrhage or diabetic macular edema. Indeed, we saw that in this data set.
We saw if you look at all vision-threatening complications, including proliferative diabetic retinopathy, anterior segment neovascular change, or diabetic macular edema, we saw that 7% in the PDS group went on to progress to that. 47% in the control group progressed to these vision-threatening complications. When we break it down into individual components, if we look at just diabetic macular edema, 7.1% in the PDS group progressed to diabetic macular edema, whereas 47% in the control group progressed to diabetic macular edema. When we look at proliferative diabetic retinopathy or neovascular change, only 1% in the PDS group progressed to that versus 42% in the control group at week 52. Let's go ahead to the next slide.
100% of the patients treated with PDS Q36 weeks did not receive supplemental treatment through week 52. You can see here, I mean, very important to kind of go over what the supplemental treatment criteria were. In this case, what would have triggered a supplement or the need for a ranibizumab injection, for example, would have been the presence of diabetic macular edema in these patients or the development of proliferative diabetic retinopathy or neovascularization as assessed by the investigator. What we saw was none of the patients in the PDS group required supplemental treatment. We saw that only 60% of the control group did not require supplemental treatment. In other words, 40% did require some degree of supplementation, or intravitreal injection, for stabilization. Let's go to the next slide.
Again, here, majority of ocular AESIs through week 52 were non-serious. Very important to note, no cases of endophthalmitis or implant dislocation were reported through week 52. Let's go to the next slide here. You know, a couple thoughts to summarize. I mean, these are reassuring data points for us. For faricimab in general, it is nice to be able to now expand potentially, hopefully, the types of patients we're able to treat today in clinic. We're treating neovascular AMD and DME, and hopefully soon we'll be treating RVO as well. With Port Delivery System, again, nice to see our diabetic patients doing well, whether they are DME patients, or another huge unmet need for us is diabetic retinopathy patients even without DME. We see them doing better as well.
This is again reassuring from our standpoint as clinicians. I'm gonna hand it over back to Bruno, I believe, for the next section.
Thanks a lot, Leo, for having taken us through the data. I think with that, we will open the Q&A session. The first one in the row is Tim Anderson from William Blair. Tim, please.
Thank you. A couple of questions that are commercial in nature, if I can. Slide 6 shows quarter post-launch data, Vabysmo beating three other brands, but it's only four quarters into the launch. I'm just wondering if there's any sort of bolus effect from patients who are non or inadequate responders that might be inflating the near term ramp, or if you think subsequent quarters will show continued quarter and quarter uptake. I'd just love to get your perspective. I know it's not your brand, but high-dose EYLEA, very relevant to the future outlook for Vabysmo. How you think this will play out commercially and change the dynamics from what they are today, once that product launches in the back half of the year?
Sure. Maybe I'll take us out. Nice to see you, Tim Anderson, again. Thanks. I think on slide 6, I think the intent there really was just to show how well is this tracking to historical norms, the launch. We've just been through a pandemic. We've seen different dynamics of clinic practice and adoption. But I think we're very encouraged by that. I don't think there's a significant bolus, so to speak. I think I mentioned that 2/3 of the switches are coming. All of the, a lot of the business coming from switches, 2/3 from the aflibercept, with patients that had persistent fluid and there's a time where you would try a new agent there.
With the safety profile being more confirmed and confident, as well as the J-code coming through with reimbursement confidence, we're seeing a greater first-line use. Our understanding, this isn't a bolus at all. Second piece, I think you talked about high-dose EYLEA. Maybe I can kind of just take a look at that. We've seen the PHOTON and PULSAR results presented. You know, what we see from that is more anti-VEGF. I think the community would like to see is more long-term data. They'd like to see more CST data in terms of anatomy moving forward. From our side, don't wanna really comment on other people's products.
What I'd like to say is that from a Vabysmo perspective, you know, this is the first bispecific antibody. We're seeing sort of increased drying. We're seeing really strong anatomical impact when patients are switched over. That's leading to kind of confidence in the durability as well as the confidence to move into first line.
Thank you.
Tim, did we answer all your questions, or you had an question also on high-dose EYLEA and how this plays out in the market? Tim? I mute you.
Yeah. Sorry. on high-dose EYLEA, well, I mean, no, you didn't really answer that question. I would just love to get your perspective for how you think that's gonna play out. I understand it's a competitor brand, but Regeneron is willing to talk often about your product, and kind of throw shade on Vabysmo, and I didn't know if you think there's particular shortcomings with their product and that sort of thing. I was giving you a chance to kind of address things that they point out with your product.
Tim, I think previously we've pointed out that some of the numbers that being used, there are occasionally kind of cross-trial comparisons. We also probably want to have a look at the importance of retreatment criteria there. What I was alluding to in terms of our practice is that in the real world, as patients, as doctors are treating their patients in clinic, we're seeing building confidence not only from switch patients, but also going into earlier lines of therapy with our product. I think you need to take that data and analyze it and scrutinize it more. In terms of playing out, you know, this is a competitive marketplace, but we've seen that Roche can be a competitive player as well.
Thank you very much.
Thanks a lot, Nilesh. The next question I will take from the Q&A here sent in. It comes from Richard Parkes, from Exane BNP Paribas. Richard is asking, can I ask Dr. Sheth to explain why the focus on macular leakage in the RVO studies, why we focus on RVO in the RVO studies rather than on anatomical measures such as CST? I'm trying to understand the relative importance of those measures to physicians in managing RVO patients.
Yeah. Great question. I think for us, when we look at new mechanisms of action, what we really wanna know is, you know, what impact does that anti-Ang-2 effect have in our patients. This is one of the trials where we actually looked at that. I think that's why, one, it's an important point to highlight. The second is, you know, if we're looking at CST thickness, we want to see... We're only looking here at week 24 data. So it's hard to make kind of anatomic assessments in that short period of time. We're just looking for any signals. To me, this was a nice signal to see that this mechanism of action is potentially impacting us.
The good thing is that Roche is doing a good job of looking at this more specifically in future clinical trials. There's a diabetic macular trial that's going on right now, looking at anatomic change. From my standpoint, this is kind of the first signal we're seeing, and hopefully first of many to come. I think for me, that's personally why I'm looking at this and whether we're really differentiating or not in the real world.
Thanks, Vidal. Next question will come from Dominic Lunn, from Credit Suisse. Dominic, please.
Hi. Thank you. Two questions. On Vabysmo, how significant is the prefilled syringe in achieving internal ambitions for the drug? Does the current lack of prefilled syringe hold you back in any patient settings? Secondly, on the future of the PDS, it's probably fair to say that Susvimo didn't start like you hoped it would, but you do say significant progress has been made with understanding the septum dislodgement issues. I was wondering if you could elaborate on what that progress is. Vitreous hemorrhage looks higher, I just wanted to get your overall level of confidence that these issues can be addressed. Thanks.
Thanks, Dominic. Maybe I'll pick off with prefilled syringe and Vabysmo. I mean, we're fully committed to the prefilled syringe. We brought the vial to market faster, given how fast we recruited the studies and the impact we saw of bispecific, you know, inhibition of VEGF and Ang-2. We're working on that diligently. We think it's an important characteristic, you'll probably remember from the marketplace that a number of other products didn't have prefilled syringe and still gained a lot of market share and adoption based on their clinical profile, and that's what we're confident with. Having said that, I would reassure you that we're working on that quite diligently to bring the prefilled syringe forward. It will make it easier for practices to adopt.
On the Port Delivery System, in terms of launch, actually, our launch was relatively in line. We'd always wanted a purposeful launch. You know, there's this is a very different setting to the intravitreal setting, which has had many years of practice and patterns adopted. I think it's gonna be really important that we train on the surgical procedure. Obviously, we were, you know, disappointed to have to voluntarily withdraw the product. I think that the launch was relatively well considered. We had more than the number of patient doctors that we had anticipated trained on the surgery, so we're looking forward to relaunching that product as we move forward. Your third question on the hemorrhages, I'd like maybe to address to Christopher Brittain or Veeral Sheth.
Yeah. Perhaps I can take that one. Yeah, so great question. Yes, as you recall, in our phase II, in our phase II neovascular AMD study, there were issues with vitreous hemorrhage. We then optimized the surgical procedure, and that rate of vitreous hemorrhage came down significantly in the phase III Arch way study neovascular AMD. Now, when we look at the diabetic macular edema population, I'll give you an example of the Pagoda study. There were a number of vitreous hemorrhages. However, it's really good news in that the vast majority were mild or moderate in severity, as in 90%, so 28 out of the 31 cases were mild or moderate, and the vast majority recovering or recovered already, as in 94% at the time point of the data cut.
Only three events of vitreous hemorrhage actually required an additional procedure. The surgical training in terms of the outcomes for patients, continues to improve and reduce the rate of vitreous hemorrhage. I think this is being managed very nicely. I mean, from a clinical perspective, Veeral, do you want to make any comment on those numbers?
You know, I think that's exactly right. I mean, even if there was one red blood cell, we had to classify it as a vitreous hemorrhage, and the vast majority of these were mild to moderate, as you mentioned, Chris. I think practically speaking, we always expect, you know, something like that, but I think the rates and signals are pretty low.
Mm-hmm. Okay.
Okay. Thank you.
Can move on. The next questions would come from Matthew Weston from Credit Suisse as well. Matthew.
Thanks, Bruno. I was gonna say full corp press from Credit Suisse. Two questions please, if I can. The first is just a very simple commercial one. Given that the launch is clearly progressing ahead of expectations, can you give us a confirmation that you have the manufacturing capacity to sustain the launch at the current trajectory? Secondly, a question for Dr. Sheth, if I can. Dr. Sheth, it's always hard when we ask you to speak on behalf of a community of physicians, many of whom are gonna do different things.
The other dynamic that we're gonna have in the industry coming up soon is biosimilar LUCENTIS, and I would be very interested how you see it playing out in terms of the balance of patients who are likely to see, let's call them marketed brands, and those who are likely to move to what are probably gonna be cheaper alternatives in terms of biosimilars.
Did you mean Matthew biosimilar LUCENTIS or biosimilar EYLEA as well?
Well, any of the above.
Okay.
Thanks, Matthew. Maybe I'll take the first question then hand over to Veeral on the practice anyway. Yeah, no, thanks for the question on Vabysmo. Yeah, the launch is progressing very well. In terms of your question on manufacturing capacity, I think we have really confident sufficient supplies of Vabysmo available. We're looking forward to doctors adopting it more and more and testing that, but we're very confident and able to supply the vials as the uptake grows. One comment just before we move to Veeral on...
In this marketplace, and I've commented on it before, you know, we're really looking forward to seeing and learning about biosimilar adoption in a marketplace like this where other products have been used that aren't licensed as well at very cost-effective prices. I'll hand over to Veeral in that context.
Yeah, Matthew, great question. I mean, I just got back from a meeting where we were discussing biosimilars. I think what I will tell you is there is very little consensus on how we're going to be using them or deploy them. In fact, I'll go one step further and say there's still a lot of confusion on how to incorporate biosimilars into our practice. Just from a personal standpoint and in our own practice, we have not really looked at using biosimilars just yet. I think there's a lot of aspects to that. I think we like the options we have. We like the on-label options.
you know, once you start introducing new treatments, there's stocking issues, there's, you know, payer issues, all these other things that we have to deal with, and we're still hesitant to kind of open that Pandora's box. I would say right now, to your point, there is really no consensus in our practice community or, you know, in our microcosm of our practice alone. I would say I think certain things will drive it. Payer, you know, payers asking for step edits and things like that may drive that a little bit. Right now we are not looking at using a lot of that.
Matthew, did we answer all your questions?
Yeah, that was everything. Thank you very much indeed.
Okay. The next one would be Simon Baker from Redburn.
Thank you, Bruno, for taking questions. Louis, if I may, just going back to Vabysmo, and the questions that Tim and Matthew asked. It does indeed look like the launch is going extremely well. I just wonder if you could tell us if there are any remaining gating factors on access and coverage in major markets that you still have to overcome for Vabysmo. Secondly, on the IL-6, one of the hypotheses that has emerged on glaucoma in recent years is that there's an autoimmune dimension to it, mediated by T cells. Now, if that's indeed true, then an anti-IL-6 could have a beneficial effect in reducing T cell activation.
I just wondered what your thoughts were on the autoimmune dimension to glaucoma and the potential for your IL-6, if indeed there is one there. Finally, just a quick update on LUXTURNA. Didn't see it in the presentation, didn't see it in the annual report, I just wonder if you could tell us where we are with LUXTURNA. Thanks so much.
Sure. Thanks. Thanks so much, Simon. Maybe I'll take the first question on the Vabysmo and the reimbursement landscape. Maybe Chris then, hand over to you for IL-6 and glaucoma, maybe Bruno, you can comment on Spark and LUXTURNA, if that's okay, from our side. It's a great question. You know, we're really encouraged that in 11 months we have 8-9 national reimbursements that have occurred since the approval of Vabysmo. There are still a number of negotiations ongoing, Simon. Predominantly, France, Italy, Spain are still to come on board. That plus other countries out into Europe and around the world.
you know, approvals for the Vabysmo in Europe was September last year, so you can imagine that that's an ongoing process. More to come on that, but we're really encouraged by the fast adoption and payer recognition of the value Vabysmo brings in this short period of time. Does that answer your question?
Yeah.
I can hand over to Chris.
Yeah. No, sure. That was great. Thank you. Are there any additional hurdles to clear in the U.S.?
Permanent J-code I think was achieved in October. I think it's just local reimbursement that we're working through. Not in the U.S.
Okay. Maybe I'll answer roughly the good question, Simon, on IL-6 and use in glaucoma. Taking a step back, just as a reminder, we are a company who's like firmly established, we believe now in retina globally, and we're looking forward to expanding to novel indications across ophthalmology, which includes glaucoma and other front of the eye indications. Within glaucoma, we see kind of two broad unmet needs. Number one is better delivery of intraocular pressure-lowering therapeutics, by which I mean long-acting delivery to reduce the burden on patients of daily drops from multiple bottles. The second is around neuroprotection. Clearly there are challenges with both, otherwise they'd have been developed already.
Specifically on the IL-6, to your question around T cell and autoimmune, autoimmunity, I'd say right now we are currently looking at all potential opportunities for the use of IL-6 in all indications. We've not made any firm decisions, but certainly glaucoma would be one that we will be looking at in more detail to understand better the science behind that discussion. Thank you for the question, but I can't really give you anything concrete except to say that yes, certainly very interested in glaucoma therapeutics.
Maybe to finish from my side, Simon, I think there's not a lot I can say on Luxturna. I think we... it's still on the market and available for patients. I think we have a sales, which we have not broken out, which are on the CHF low double-digit million range, and we would expect it to remain roughly in, you know, in this sales range.
Great. Thanks so much.
Yeah.
We would move on, and the next question would come from Peter Welford from Jefferies. Peter, please.
Hi. Thanks for taking my question. just a couple left. firstly, just returning, I guess to maybe Dr. Scheidl just with regards to his practice. Again, appreciate Matthew's comments, well, this is not necessarily the consensus as a whole, but can you just talk a little bit about the type of patient in particular that you've put on Vabysmo so far? We appreciate the data, obviously, that Roche has given. Can you talk about, you know, for you, does your personal practice, you know, generally mirror this? And I guess perhaps more importantly, at what stage are you at with regards to considering putting a patient first line newly diagnosed in your office straight onto Vabysmo as their therapy of choice? and perhaps, you know, what do you need to see to get there?
Second thing, can I just ask with regards to the Port Delivery System, can I ask whether or not, you know, potentially with that you think there is a risk here of a, I guess, I don't know what the right word to use is, but I guess false start in the sense, you know, we've seen this before in the eye market where companies have, you know, had an issue then at launch and have had to sort of go and sort of revise and restart again.
I guess, what do you think the risk is with Susvimo at this point, that because of what they've seen with the device deficiencies that actually, you know, to rebuild confidence in the medical community, what steps need to be potentially done to be able to do that? Thirdly, just returning to Luxturna, can I just ask you more broadly, do you have any plans to go gene therapy in this market, or do you believe that, you know, due to fabs and the implants are more than sufficient and actually a longer-term gene therapy sort of approach is frankly, you know, not avoided at this point? Just finally, can I ask you just on the GA market, what Roche's sort of thoughts are on this?
I think there's been a lot written in terms of how this market could potentially develop over time as new therapies come. You know, are you worried about being, I guess, a latecomer to this market? What do you think you can bring that perhaps won't be addressed by the time you get to market with the GA therapy? Thank you.
Great. Thanks. Viral, do you wanna answer on the first question?
Yeah. Yeah, I will take that, the first of the four parts there. Peter, I think your question really is around practice patterns and, you know, we're really kind of approaching or have just approached the one-year anniversary of having Vabysmo approved in our offices here in the U.S. What I can tell you is the initial patients that we used Vabysmo on were switch patients. The majority of those being patients switched from EYLEA. These are patients that probably had some persistent subretinal or intraretinal fluid, or patients that we just could not extend beyond six, eight weeks, for example, was kind of the majority of the patients that we switched over initially. I think like anything else that's new, we learn a lot from those patients.
We saw, you know, a smooth transition for those patients. We saw a good number of them do better clinically. A lot of those patients are reflected in the TRUCKEE data set that you saw earlier today. I think, we've since transitioned patients that are not just switching from EYLEA that are not doing as well, but we're switching some more patients over where we're looking at that durability effect, trying to get those 8-weekers out to 10 weeks or 10-weekers out to 12 weeks. That was kind of the phase II of our implementation. Now we're at the point where we certainly are comfortable using Vabysmo as first line for our neovascular AMD.
Once the J-code became available, more of our diabetic macular edema patients kind of got rolled into that, just from a payer perspective and being able to make sure we have coverage for that. Certainly I think at this point, I just pulled the data last week from our own clinic. Personally, I'm using about just over 50% of my patients, receiving on-label injections are Vabysmo. We kind of just crossed that threshold with a number of kind of new patients now being started on Vabysmo as first line.
Okay. I think we move to the question on port delivery. Peter, if that answers your question.
Yep. Sorry, I couldn't mute this up. Yes. Yeah, that's great. Thank you.
Port delivery. I think one thing to note, and I'll invite Pierre-Alain to comment on anything additional. It's a great question about, you know, false starts or not. First of all, as I mentioned earlier, you know, we definitely wanted a purposeful launch for this product. Secondly, something to note, a lot of the false starts that you may be remembering had safety issues. This is not a safety issue per se. This is a manufacturing variability issue. Is the second point to note, and we're still looking to do that. The patient preference data we see, the physician adoption data for the patients that they have on Port Delivery System is still highly positive. I mean, and maybe Viral can even comment on that, but certain patients we...
certain physicians we speak to, you know, requesting the Port Delivery System back because their patients want the Port Delivery in their fellow eye when they get the launch. There's preference there. Third is the competitive dynamics in this marketplace. There's very little that's similar to this, and in other false starts, there's been alternatives. I think it is different. We're not at all being complacent about that. We're taking really responsible, thoughtful decisions about how we bring that back. We think the unmet need for durability and consistent outcomes is very high. We're not seeing anything approaching 6 months durability or 9 months durability with anything like the consistency of both visual acuity or anatomy that we're seeing with Port Delivery. It is an investment up front in terms of the surgical implant.
We're very confident to bring this back, and we're planning quite a lot of pipeline around it. Pierre-Alain, I don't know if you wish to add anything to that.
No, it's, we, it's very clear what the technical challenge is. We have multiple product specification standards, and we have one single of these standards where we have an issue. The teams are working currently to understand the source of the problem, and we have already some improvements options in front of us. We are currently doing the testing, and it's just a matter of time until we are back with a product meeting the specification.
Maybe, Veeral, if I can put you on the spot just to ask you to comment on your perception on how the recall's been handled and how you're planning to work it, maybe to add context for Peter.
I mean, I appreciate, you know, the level of concern in how Genentech Roche has handled the recall and the level of transparency that we have as providers. You know, I think, Neil, actually you made the point about patients that have received it in one eye kind of requesting the second eye. We experience that routinely in our patients. Again, we were in a number of the clinical trials, a lot of those patients, if they haven't received the fellow eye, they are asking and looking forward to receiving it. That has been our kind of experience with it as well. Certainly, you know, when it does come back to us, we're looking forward to restarting that process again.
Thank you. I think, Peter, your third question around gene therapy and whether there's still interest in that, maybe Chris, you wanna take that from a development perspective.
Thanks, Nilesh. Thanks, Peter. Great question. The answer put simply is yes, we are still robustly interested, and we have active research programs ongoing in gene therapy. I think currently what we see in the later stages of other companies' development programs, there remain issues and concerns around intraocular inflammation. We see both, you know, cells in the vitreous and also there's concerns around mottling of the retina, which may or may not be related to some sort of localized inflammation or overactivity of the RP. That's still to be understood fully.
I would describe our approach as probably looking for more the second generation or arguably the third generation of capsids to kind of really reduce that immunological concern based on these capsids. Yes, the answer is very much remaining very interested in gene therapy. I think I mentioned earlier on, you know, we have, we did the recent deal with Avista to acquire their capsids, and we're looking actively at, in optogenetic approaches.
I think your final one, Peter, if that addresses the previous, is around the GA landscape a little bit and how we view that, and maybe I'll start and then Chris or anyone else would like to comment on this. First of all, as Chris mentioned, this is an area of high unmet need for us. There's no therapies right now. We're anticipating some therapies coming forward. As we look at that, we think of that as a starting point in the journey. You know, treating patients that are asymptomatic with repeated injections is going to be something that the field will adapt to. Second piece is that a number of these products also have adverse events associated with them in terms of CNV formation as they're moving.
As we're looking at this, you know, we're looking that even if we're a following player in this area, depending on the profile of the product and what we can offer patients, as you know, we're focused on innovation at Roche here. We think that there's sufficient market size for that, given the unmet need and the promise of the profile that we see of the products that are currently, you know, being considered. I don't know if either Chris or Veeral want to comment further on that.
Maybe just one quick comment. Just kind of, again, just to reiterate what I said earlier. You know, we have the Ionis complement factor B program, and that's potentially differentiated through subcutaneous injections which would treat both eyes and potentially the patient can self-treat at home in the future if that treatment is efficacious and safe. You know, two great ways to differentiate. It reduces the monthly treatment burden of having bilateral, potentially simultaneous intraocular injections, which is a real challenge for patients of this age and their caregivers. That's one. Then the second, obviously the second molecule, which is the OpRegen program, the cell therapy. A number of years off, I recognize, but potentially restoring visual function and anatomy. Not just kind of reducing the rate of progression.
I'd say that's kind of our position on GA. Viro, over to you.
I'll just make a quick additional comment. I think, you know, GA is such a wide-open space still, I think, and it's such a multifactorial disease that I don't think there's really, you know... I think there's a lot of room here to achieve something that's successful. To Chris's point, different ways of addressing this, whether it's systemic therapies, different local therapy approaches. You know, I think the great thing is that, you know, we've been part of the previous LAMPA studies, and I think Genentech has a very long history with this and a deep understanding of it. So I think what they're developing is exciting and certainly we'll have some space in this, in this area.
Thanks, Veeral. Peter, did we address all your questions?
Yes. Thanks, Nilesh.
Okay. Next questions would come from Emmanuel Papadakis from Deutsche Bank.
Thank you for taking the questions. A couple of follow-ups on geographic atrophy, please. Perhaps you could just elaborate on when we're likely to see the first phase II data from the factor B and OpRegen studies. It sounds like OpRegen is some years away, but maybe the factor B sooner. Indeed, what's your confidence on improving upon the data we've seen so far from the complement molecules you have alluded to, which are due regulatory decisions fairly shortly, potentially. Then second question related, but it sounds like from your comments, the room to improve is perhaps more around formulation presentation rather than mechanism. Is there any comment you can make on the mechanism for RG6312, which is in phase I?
Can you give us any color on why you discontinued the HTRA1 molecule last year, galegenimab, after the phase II study was apparently negative? Thank you.
Chris, do you wanna take the GA questions?
Sure. First one around the timing of the complement factor B program. We'd expect phase II results in 2024, so next year for those. In terms of the OpRegen, we're just in the process of starting the phase II program. I'd probably give a kind of a year range, you know, 2026 potentially for 2026. A number of years away from the phase II reading out for the OpRegen program.
In terms of galegenimab, just going, jumping a couple of questions forward, that program, so the GALAGO study was terminated at the end of last year due to an interim analysis in which the data safety monitoring board found that there was Not an opportunity for the program to demonstrate efficacy, bearing in mind the safety which we've demonstrated at the same time. We will be sharing more details of that program at an upcoming congress. More to come from that program. I'm terrible with numbers. RG6312. Just have a quick look, but anything to add, Nilesh, in the meantime?
I think you added it on H CRA. We know this is a very difficult space and we'll continue to innovate there. You know, as programs, you know, don't have the right risk benefit, we'll be closing them down and moving our resources to other areas of investigation. I think Veeral also mentioned that, you know, the LAMPA studies, you know, whilst they weren't the result we were looking for, are a massively useful dataset for further research to continue. I'm really pleased that as a company, we've continued to share that data and interrogate that for the community to build on those learnings.
Emmanuel, could we address all your questions?
Yeah. Perhaps my only follow would be around the factor B, where you're expecting that phase II data next year. Is your confidence really in offering a more convenient solution to patients, or you're actually hoping to see something on efficacy relative to the peers that are in development? Thank you.
Sure. I find it unlikely that we'll have superior clinical efficacy outcomes. I don't think that's a realistic outcome. I think in terms of the best for patients is the convenience in terms of subcutaneous at-home injection and bilateral treatment. I don't think there's a strong belief they would have superior clinical efficacy.
Clear. Thank you.
Okay.
Just for your final one, I think RG6120 is the bevacizumab DutaFab. I think Chris had mentioned that's the most advanced towards clinic in the Port Delivery System. It's the first of our platform.
Thanks, Nilesh. The next questions will come from Peter Welford from Jefferies. Peter, please.
Yeah. Can you hear me?
Yeah. Yeah, we can.
Yeah. Thanks. Thanks very much, Bruno. Just a very basic question. In terms of Vabysmo peak sales, what do you think is the precedent? Is this more LUCENTIS or is this more EYLEA in terms of peak sales? In that context, are you confident with your marketing resources on the ground, ex-U.S. for Vabysmo? The second question is, it's also very basic, is on Susvimo. On Susvimo what actually happens if a patient does not return for refills? That's it. These are my questions.
Thanks, Marcel. Maybe I'll address a couple of the Vabysmo questions. I think the two you had, one is about ambition and the second is about commitment and on the ground. In terms of ambition, I think we would like to see this and we think that We're confident in the profile to become a standard of care in the IVT setting for retinal conditions here. You know, I think you can take from that our ambition is quite significant. Second, in terms of boots on ground, I think we've demonstrated as a company that, you know, as we see even into competitive markets, we have the ability to ramp up, address access issues and drive adoption.
We're already seeing elements of that from a number of countries. Obviously that's work in progress, but I'm really confident that the organization is flexing towards the opportunity that we see here. On top of that, I think, Chris, the next question may be for you.
Thanks Marcel for the question. This is around what happens if a patient does not return for a refill with Susvimo. I'll describe the two sets of patients. They're trial patients currently, and we are continuing to see all trial patients, and they are continuing to have refills provided within the clinical trial. For those in the U.S. who were implanted from commercial stock prior to the recall, again, they are still able to have refills because we're still providing stock for those patients to be refilled with. As a reminder, previously in our phase II study, you know, Half of patients actually made it out to 15 months prior to requiring a refill. There is a key safety margin if a patient misses an appointment.
That said, the benefits of Susvimo are that you have these robust, clear, known effects and consistency of outcomes for patients if they have regular refills. That's the true benefit of Susvimo. I think in answer to your question, what happens if they don't return? They will still get some treatment ongoing because there remains some drug within the device and the physicians tend to kind of follow up these patients. I mean, anything to add? Maybe Viral and then maybe Pierre-Alain, if there's anything else afterwards.
Yeah. I mean, I think.
Clinically speaking, you know, compliance is always an issue. Patients, you know, have other issues that they have to deal with. From my standpoint, this is one of the reassuring aspects of having a Port Delivery System implemented in these patients, is that, you know, if they're just getting intravitreal injections, for example, we see a number of those patients, and historically, over the last 15 years, have had a number of those patients not come back after a while and then come back and things are not so good, especially in our diabetic patients. I expect less of that to happen when Port Delivery is involved and Susvimo is involved. That's, I think, from my standpoint, a reason for these types of platforms.
Thanks, Will. Oh, Pierre, do you want to? No. Okay, maybe just Marcel to add from my side. I think, you asked also about, explicitly about peak sales, we don't guide for peak sales. I think I just can say, you know, consensus is still looking at the number of 3.5 billion CHF, I think we have been communicating before that we are a bit more optimistic than that number. I think nothing has changed on our side. I think really the launch is going, yeah, along the lines as we would have hoped for.
Well, that's, I'm not asking for a number. It's just U.S. versus rest of the world peak sales.
The split. The relative split.
Mm-hmm
U.S. versus ex-U.S. maybe Nilesh could provide some insights here on how the split would play out.
Yeah. I mean, you know, we know that the U.S. is the largest market in the world right now. It's probably about 65%- 35%, depending on the agent. I think we expect our launch to mirror the worldwide use.
Can you, if you allow a last question, can you talk a bit about pricing U.S. versus U.K.? Obviously, NICE has quickly endorsed the product because it saves a lot of healthcare resources. In other countries that may play less of a role. In that context, can you give us an indication about the effective price that you can charge in a country like the U.K.?
Yeah. We don't comment actually on pricing, but I think what we can comment on is that we've had about 8 or 9 countries that have national reimbursement, and they're quite different systems. You know, from U.S to U.K. to Switzerland to Japan to Australia. They will be based on being able to get broad access into those, to those markets. We're not seeing any particular challenge based on the profile that we've shown, the consistency of the data that we've shown in phase III, and augmented by the real-world evidence that we shared some of there. Yes, there are differing prices around the world. But we're not seeing any particular problem on that.
You know, I think the one thing we're encouraged by is how quickly the adoption in reimbursement has been achieved based on the recognition of the value that we're seeing from Vabysmo.
Many thanks.
Thank you.
Okay. Next one on the row would be Sachin Jain from Bank of America. Sachin, please.
Hi there. Thanks for taking my questions. A few for Dr. Sheth, if I may, on the Vabysmo Eylea dynamic. The first question is, I think we've referenced 2/3 of Vabysmo patients are Eylea switches. I know Nilesh provided his perspective on high-dose Eylea, but I wonder if you could provide yours. When high-dose Eylea is available, how easy is it to uptitrate a patient to high dose to try and extend versus switch that patient? Like, is that a dynamic that you would think about, and how would that impact your usage? Secondly, have you had any switchbacks to EYLEA from patients who've been on Vabysmo for any particular reason, safety, duration? Then thirdly, how is your injection interval with Vabysmo faring relative to what you've seen in clinical trials, i.e.
are you achieving the extension of 2, 3 weeks or more versus EYLEA, that has been touted in the clinical studies? Just one, for Nilesh, maybe Bruno. You talked about obviously successful launch ongoing. I wonder if you could just provide any soft color around that. We've obviously in the launch to date seen sequential acceleration each quarter. Are you continuing to see that sequential acceleration? Are there any factors that would cap that as we think through the course of this year? Thank you very much.
Sure. Yeah. I can take the first part of that question, which is, Sachin, I think your question was more around if and when high-dose EYLEA does become available, how do we transition patients? How do we ramp patients up? Something to that extent. I think, you know, I think we've learned a lot from the most recent launches, bevacizumab being one or brolucizumab being one and then Vabysmo obviously. I think the point is that when we switch patients, these are patients that aren't in the clinical trials, right? We're not seeing patients that are actively being managed and then switched to a new agent. This is kind of a different world.
It's not data that we know or understand because it's never been presented in clinical trials. A lot of it is trial and error. A lot of it is when these agents do become available to us, we have to see for ourselves how they work in patients that are already being treated with a different agent. I think it's tough to answer your question of how we're going to implement high-dose EYLEA and what I think is going to happen or predict, you know, potential splits with that, because I have not used it in a patient that has been previously treated with another agent. I think just to give you insight on how I will roll that out, that's probably how I will roll that out, right?
Similar patient profile to what I described earlier with the patients that were switched to Vabysmo. I think there was another question in there on splits. Sachin, can you just kind of?
Yeah, sure.
Which-
Yeah, sure. Just injection intervals, what are you achieving in real life versus-?
Yeah.
clinical trial?
Yeah. Okay. We're still learning a lot with this as well. Initially, I was keeping the interval the same when I was switching the agent. In some patients, we have extended now and had time to kind of see how the medication's working and extended them out. I think you'll see that data reflected in the future TRUCKEE data sets. I think. Oh, you had another question about have I switched people back from Vabysmo to EYLEA? Not because of efficacy issues, if that's the question. I think there might be other issues, coverage and things like that, but not because of efficacy issues.
Thank you. There was one from Nilesh.
Hi, Sachin. Nice to hear you again. We're really confident that the launch is going on, the quarter-by-quarter acceleration, especially after the J-code. I think we're continuing to see. You asked about headwinds. I think some of the uncertainties remain around the market. Things that have affected us significantly being additional lockdowns, et cetera, which have affected the whole market, so that can happen. Aside from that, I think that the profile we're seeing and the adoption we're seeing, I anticipate greater acceleration as new markets come on board as well, whilst the U.S. continues to grow on their trajectory that they're showing at the moment.
Aside from other lockdowns and/or, you know, unanticipated use, let's say, that we're not seeing from biosimilars, we don't see huge challenges on that side. As you probably know, the tailwinds for this marketplace are the EPI and that's continuing to grow and we're seeing that in the figures, you know, quarter on quarter as more patients come into treatment. Thank you.
Okay. If there are no additional questions, I think we would be at the end of our event today. I would like to use the opportunity to thank again all the speakers and also the panelists for their time and commitment, and also the IR team members who were involved in preparing the slide decks and putting everything together. This was Loren Kalm and Anita Tang, and also Sonya for organizing. I hope this event was helpful in summarizing our ambitions here for the ophthalmology franchise. If there are any remaining questions, then please feel free to reach out to the IR team anytime, and we will follow up with the teams. Other than that, I would like to wish you a good day and hopefully talk to you soon. Bye.