Ladies and gentlemen, welcome to Roche's Angiogenesis 2022 meeting. My name is Marco, and I am 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 presentations, there will be a question and answer session. You are 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.
At this time, it is my pleasure to introduce you to Bruno Eschli, Head of Investor Relations. Bruno, the stage is yours.
Thanks, Marco. Can I have the first slide, please? Next one, please. Welcome to our event, and let me quickly guide you through today's agenda. We have three speakers with us. First of all, Nilesh Mehta, our Global Franchise Head in Ophthalmology. He will present an update on our overall franchise strategy. Then we have Christopher Brittain with us, our Vice President and Global Head of Ophthalmology Product Development, who will provide you an update on our growing clinical development pipeline. Finally, last but not least, we have Nancy Holekamp with us, a well-known retina specialist and also a Vabysmo clinical investigator, who will lead us through the two-year data of Vabysmo and Susvimo, which we have just presented over the weekend at the Angiogenesis meeting. Overall, we have, I think, planned for 1 hour and 50 minutes.
We will have a Q&A session with all the speakers present following the presentations. I would also want to highlight here that we have a little online poll, five questions only at the beginning of the Q&A session, which I would ask you to maybe fill in. Next slide, please. I also wanted to quickly use this occasion to give an update. You know, we have a busy year ahead of us when it comes to pivotal readouts in 2022, and there is also a first green tick here on the regulatory side, which we have set, which is for Vabysmo in AMD and DME, the U.S. approval already achieved.
I also wanted to point out that on the ophthalmology side, there is two additional readouts, pivotal readouts to come later in the second half this year, which will for Susvimo in DME and diabetic retinopathy. On the bottom in the box, I also wanted to use this occasion here to highlight some events where we have been able to fix dates. The next event, virtual IR event, will be following the MDA conference. It's scheduled for the sixteenth of March, where we will present our latest data for Arystay and providing an update on our neuroscience pipeline.
Then at the sixteenth of May, we will have our first little Roche ESG day, where we will focus on the access to healthcare and equally represent both our divisions, the dia side and the pharma side. Next slide, please. Before handing over to our first speaker, I wanted to quickly share some recent external surveys from among ophthalmologists, which I found quite interesting, which focus on the remaining needs in AMD and DME. If you look to the left side, this survey result was collected among 990 U.S. and international ophthalmologists at the ASRS conference last year.
The question was, "What do you think is the biggest unmet need in wet AMD therapeutics?" What you can see here is that, the need for longer-lasting treatments was named first with around 40%, and the need for new drug pathways was named second with, around 30%. Then if you go to the right side, you see here, this was a survey conducted by Deutsche Bank last October. This was a survey amongst 41 U.S. ophthalmologists, and, they were asked again about unmet medical needs in AMD and DME. Again, dosing frequency was mentioned here on the number one position, followed by efficacy and then also by, patient access and to a lesser extent, by safety. Overall, I would say a pretty consistent picture here on the unmet need side.
Next slide, please. This is my final slide. It just shows another poll, which is just two weeks old and was published by FirstWord Pharma. This is following our Vabysmo approval in the U.S. When asked about which proportion of patients would gain meaningful benefit from fewer eye injections, the answer was again 72%. What is also interesting here on the right side is that there would be a benefit for new patients as well as for patients who could be switched from other treatments. With that intro, I would like to hand over to Nilesh, our Global Head of Ophthalmology, for his presentation. Nilesh, please.
Thank you, Bruno, and good morning and good afternoon to everybody. Allow me to add my warm welcome to you all, and thank you for joining the call on Valentine's Day. My name is Nilesh Mehta, and over the next few slides, I'd like to cover the unmet need in retina, provide an overview of the ophthalmology market with a focus on retina, discuss the recent approvals of both Susvimo and Vabysmo, which we think take us a step closer to addressing some of these unmet needs, and then close with an overview of our ongoing approach to ophthalmology innovation. Next slide, please. As you can see, despite the tremendous advances in retinal care since the advent of anti-VEGF therapies some 15 years ago, we firmly believe there remains a significant unmet need and an opportunity to improve upon patient outcomes.
Let me explain a little bit deeper. On the left-hand side here, what we see is that even in clinical trials where people with retinal disease are treated rigorously, many don't achieve 20/40 vision, which is a threshold that's usually required for driving. In the data recently presented over the weekend, only about half of patients achieve this level of vision. Further, when we move into the real world, the application of IVT treatments often cannot keep pace with disease requirements, and many more people lose vision over time. We all know that these populations will become ever more prominent in society as the world ages and the diabetes epidemic continues. On the next slide, we show that the advances in retinal treatment and the EPI factors mentioned really have made retina a key segment in the ophthalmology market.
We estimate the full market to be worth about $22 billion and the retina forming about two-thirds of that, at about $13 billion. The outlook is for growth to about $15 billion by 2025. Tailwinds being innovation and EPI, and the headwinds being biosimilar impact. If we move to the next slide. Want to focus for a moment on the real world outcomes we see. We see from data on the left of the page here that healthcare systems really vary in their ability to deliver sufficient IVT treatments, and these are really correlated with the outcomes people achieve. Today, only about 50% of patients can be extended to Q3 month dosing with current anti-VEGF IVT therapies.
We believe, really, this is where both Susvimo and Vabysmo have a role to play in allowing people with retinal disease to maintain their vision gains with fewer treatments and in a manner that healthcare systems and providers can deliver. Next slide, please. Now I'm really very pleased to update you on the recent events for Vabysmo, faricimab, and you will have noted the publication of the one-year primary data published in The Lancet. This is the first time that two major indications, neovascular AMD and DME, have been studied together in phase III, presented jointly and published simultaneously. The publications highlight the data across the four phase III studies with greater than 3,200 patients. They show that faricimab, when dosed up to 16 weeks, was consistently across the studies, shown to deliver vision outcomes that were non-inferior to aflibercept dosed every 8 weeks.
This is the first time that such a durability, supported by consistent anatomic findings, has been demonstrated in a large randomized controlled setting. On the next slide, we see that just a week after The Lancet publication, the FDA granted approval for Vabysmo for the treatment of both neovascular AMD and diabetic macular edema, and with dosing flexibility from Q4 to Q16. faricimab is under review with health authorities, including the EMA and others around the world as we speak. You're all familiar that this is the first bispecific antibody for intraocular use that simultaneously neutralizes both angiopoietin-2 and VEGF. It's engineered using Roche's proprietary CrossMAb technology, which was developed in-house within pRED, and, you know, represents more than 10 years.
We've just presented the two-year data from DME at Angiogenesis over the weekend and look forward to sharing the two-year neovascular AMD data later in the year. There are ongoing extension studies with Rhone-X and Avonelle-X for both indications, and these will provide four years of data. Further, and not to be forgotten, we have ongoing studies in retinal vein occlusion, which is the third largest indication in retina. On the next slide, I'd like to move to Susvimo. Also another focused development over more than 10 years, and it's the first and only eye implanted device providing continuous delivery of anti-VEGF and requires twice-yearly dosing, which is equivalent to 12 monthly doses of ranibizumab. Susvimo was approved by the FDA just at the back end of last year. As you can tell, it's been a fairly busy time for us, folk in ophthalmology.
We again have ongoing discussions with the EMA as well as other health authorities around the world. There's an expansive ongoing phase III trial program covering diabetic macular edema, diabetic retinopathy and also testing dosing up to nine months in neovascular AMD. Moving to the next slide, what does this really mean? As outlined, by, you know, addressing key unmet needs, we have an opportunity to improve sustained vision outcomes for people with retinal pathologies, with treatment schedules that healthcare systems can provide and which patients can manage and adhere to. With Susvimo, patients can attain outcome certainty with just two refills a year following a surgical implant procedure. With Vabysmo, about three-quarters of patients can achieve Q12, 4 times a year dosing in an IVT format.
This comes without compromising visual outcomes associated with more frequent anti-VEGF dosing, which is either every month in the Susvimo studies or every two months as studied in the Vabysmo studies. Finally, if I go to my final slide. So you know, we're really very pleased with the introductions of both Susvimo and Vabysmo in the U.S. market. Our ongoing efforts won't stop there, and I wanted to conclude by sharing some of the four pillars that guide our efforts, and continue to address unmet need. First, there'll be ongoing efforts towards novel modes of action and pathways, including DutaFab, which you'll hear more about from Chris, as well as for geographic atrophy. These aim to get more people to better outcomes by addressing pathways beyond anti-VEGF.
The number of long-acting approaches with Port Delivery System as a platform, at first, but also expanding into long-acting IVTs as well as into gene therapy, which holds so much more promise to get real-world outcomes closer to those seen in clinical trials. In addition to our significant internal R&D efforts, we're active to bring in and partner with external innovations. Ionis and the recent foray into cell-based therapies are just two examples of that. Finally, with the improvements to imaging and clinical biomarkers, we believe that the field is really poised for more specific therapeutics and management approaches in the future. All of this makes this such an exciting time to be in ophthalmology. Thank you for your attention. I'll hand over to Chris to overview some of these in greater detail.
Great. Thank you, Nilesh. As you've heard from Nilesh, one of the opportunities that we've been given here at Roche is to recognize that ophthalmology has actually become one of the three core areas for investment, the others being oncology and neurology. In the next few minutes and before Dr. Holekamp talks us through the newest data, I really want to explain how we're looking at the future opportunities which we intend to utilize to improve patient outcomes and reduce the burden of retinal disease on them, their caregivers and healthcare systems.
Looking at the next slide, after the launch of Susvimo in the U.S. last year, the launch of Vabysmo just in the last couple of weeks and some of the exciting quotes which we heard over the weekend as we presented some of these two-year data at the Angiogenesis Conference, such as, "Very impressive data. Can't wait to get my hands on this drug," and, "Makes us think we have a new gold standard." I'm actually really pleased that we're gonna have a continued flow of exciting data in the near and upcoming future. Starting, as you can see, in 2023, we're gonna potentially be filing, as Nilesh has already implied, potential filing opportunities for Vabysmo in both CRVO, so central retinal vein and branch retinal vein occlusion.
For Susvimo in patients with diabetic macular edema and diabetic retinopathy, with treatment intervals going out as infrequently as 9 months with a Pavilion diabetic retinopathy study. Then beyond that, we have further in the coming years two of our exciting programs in geographic atrophy, just to call out to the anti-HTRA1 and the Ionis complement factor B inhibitor, about which we'll talk a little bit more later on. As you can see, there are a number of additional phase I programs in both diabetic macular edema, GA and neovascular AMD. Now if we just move on to the next slide. As a reminder, which Nilesh has already spoken to, Vabysmo is a true bispecific molecule, targets two distinct pathways, aims to reduce vascular leakage and inhibit neovascularization through the established anti-VEGF pathway.
While the anti-angiopoietin pathway also enables stabilization of vessels, reduce vascular leakage and inflammation. As you'll see in Dr. Holekamp's presentation, this dual inhibition has led to even more durable efficacy in the long term in our phase III DME program. Moving on to the next slide.
Recording in progress.
On the significant unmet need which remains for patients with geographic atrophy. On the next slide, I just want to spend a minute talking a little bit about the DutaFab platform. As you can see, DutaFabs enable the binding of multiple targets from two or more distinct pathways. These are both highly potent and stable. This in turn allows high doses for both intravitreal injections and compatibility with the Port Delivery System. The most advanced example is our VEGF/Ang-2 DutaFab, which is in phase I currently in patients with neovascular AMD, and which will be moving into the Port Delivery System. The next slide. This moves us on to the Port Delivery System platform, which as a reminder, is designed to continuously deliver therapeutics through first order passive diffusion kinetics.
The concentration of ranibizumab in Susvimo, as we know, is 100 milligrams per mL. I hope you can start to see why new therapies that are potentially higher in concentration and bispecific in nature have the potential to take this platform play to the next level. Moving on to the next slide to discuss briefly geographic atrophy. As you know, geographic atrophy is an advanced form of age-related macular degeneration and affects the elder generation at exponentially increasing rates, rising from about 1% at the age of 70 to over 10% of patients in their eighties. The number of complement and non-complement associated genetic markers that impact environmental stressors and pathological findings, including the presence of lipids and amyloid within the retina. This is a disease that will likely require combination therapies in the future.
On the next slide, you will see how we are approaching this. We're approaching it by having currently four programs ongoing, three of which are discussed here. The first one at the top utilizes the Anti-HtrA1 serine protease as an intravitreal injection, and that is in phase II. The second program is our partnership with Ionis, which utilizes a subcutaneous injection of complement factor B. By targeting the liver, which is the source of complement factor B, this approach potentially enables simultaneous bilateral treatment effects for patients with bilateral geographic atrophy. At the bottom, you will have seen in the last few months, our recent deal was with Lineage Cell Therapeutics, and we're really excited about the potential of this allogeneic RPE cell therapy to enable us to take a step towards restoration of retinal structure and improvement in vision.
This would be a real step change because as currently the current study programs and therapeutics in studies are aimed simply at reducing the rate of disease progression. Next slide. In summary, I'm sure I hope to share with you that with our execution of the launches of Vabysmo and Susvimo on track, our expansive pipeline is also setting us up for a really exciting future of possible treatment options for patients with retinal disease. Now it's actually a great pleasure to ask Nancy Holekamp, retinal specialist, professor of clinical ophthalmology and visual sciences at Washington University School of Medicine in St. Louis, and the director of retinal services at the Pepose Vision Institute. Most importantly, a very experienced principal investigator across many of our programs, including Susvimo and Vabysmo, to talk through some of the new two-year data.
Thank you, Dr. Holekamp.
Well, thank you, Chris. Thank you for that introduction. It is my pleasure to be here to talk about the Vabysmo DME two-year data set and the Susvimo neovascular AMD 2-year data set. Next slide. We're gonna begin with faricimab in diabetic macular edema. Again, the two-year results from the phase III YOSEMITE and RHINE trials. This was presented by Jack Wells on Saturday at the Angiogenesis meeting on behalf of the YOSEMITE and RHINE investigators, and I was quite pleased to be a YOSEMITE investigator. Next slide. First, we're going to look at the clinical trial design. YOSEMITE and RHINE investigated faricimab dosed either Q8 weeks or dosed as a treat and extend dosing posology called a personalized treatment interval with up to Q16-week intervals. Both of these trials were large phase III randomized, double-masked, active comparator-controlled trials.
In fact, combined, they looked at over 1,800 patients with center-involved DME and best-corrected visual acuity between 20/40 and 20/320. These patients were randomized equally to one of three treatment arms. At the top, we see faricimab dosed Q8 weeks after six loading doses. We then have faricimab dosed according to this personalized treatment interval after four loading doses. The active comparator was on-label dosing of aflibercept every 8 weeks after five loading doses. Of importance to this clinical trial design is the faricimab 8-week arm, which offers a direct comparison to the aflibercept Q8-week dosing arm, with the only difference of that additional loading dose. We also see that the primary endpoint was an average of change in best-corrected visual acuity averaged over weeks 48, 52, and 56.
At the study end, which we will share today, is the average of change in best-corrected visual acuity averaged over weeks 92, 96, and 100. Next slide. Just a word about this personalized treatment interval algorithm. This is a protocol-driven treat and extend regimen. Essentially, it's doing what we clinicians, we retina specialists do in our clinics in the real world under the auspices of a clinical trial. Importantly, decisions are based on both changes in central subfield thickness or anatomical changes and best-corrected visual acuity. There's an initiation phase where patients receive four initial Q 4-week dosing, and if their CST is less than 325 microns, they go to the PTI phase. If the CST is improved, you maintain the treatment interval.
If the CST is stable compared to the reference CST, you can extend the interval by four weeks up to Q 16 weeks unless there is a significant decline in vision of 10 letters or more. If the CST is worsening, if vision is unchanged, you can maintain the interval, but if vision is worse, you can reduce the interval by either four weeks or eight weeks. Again, this was a way of approximating what we retina specialists are doing in the real world. Next slide, please. It's important to note that baseline patient characteristics were well-balanced across the treatment arms and that the patients enrolled in YOSEMITE and RHINE really mirror or match what we see in clinical practice. Patients with DME tend to be in their early 60s. They experience moderate vision loss, and the median vision here was equivalent to about 20/50.
The retinas are very thick, with the CST measurements being in the high 400s. Next slide. We've seen this data before. This is the one-year data that was just published in The Lancet, and we see vision gains with faricimab dosed every Q8 weeks and PTI up to Q16 weeks. They were non-inferior to aflibercept dosed Q8 weeks. If we build the slide, we'll see that these vision gains are maintained through year two. Importantly, these visual acuity lines are on top of each other, and we see that there are no clinically meaningful differences when we compare all the arms across both trials. In fact, visual acuity improvements were robust, ranging from 9.4 letters to 11.4 letters. Next slide, please.
Now we wanna look at durability, and we wanna look at durability in the faricimab PTI arm. We already know this from the data released at week 52, that approximately 50% of patients in the faricimab PTI arm could be dosed at Q16 weeks. Next slide. Now we have data through week 96, and we see that the proportion of patients who achieved faricimab Q16-week dosing actually increased to greater than 60% by week 96. If we look at the percentage of patients who could be dosed at those extended intervals of Q12 weeks and Q16 weeks, the number was 78.1% of patients in both YOSEMITE and RHINE. When we look at the median number of injections in year two, that means that the PTI arm was receiving three injections on average in year two.
Now, a critical question is, for those patients who achieved Q 12-week or Q 16-week dosing at week 52, what percentage of those patients could maintain that extended dosing interval until week 96? That answer is 79%. If we only look at Q 16-week dosing and ask ourselves what percentage of patients could stay at that interval without having to contract or shorten the dosing interval, that number was 76%. The excellent durability of these extended treatment dosing intervals through week 96. Next slide. When we talk about extended dosing intervals, we wanna make sure that we're not placing patients at risk for not being the big winners, not getting that greater than or equal to 15 ETDRS letter gain at two years.
On the left-hand side of this slide, we see that these results are balanced across the treatment arms of both studies. On the right-hand side, we're answering a slightly different question. We really don't want to have fewer doses and expose our patients to severe vision loss as determined by losing greater than or equal to 15 ETDRS letters at two years. We see that's not the case. The vision is maintained and preserved across all treatment arms, including the faricimab PTI arm at two years. Next slide, please. Now we're gonna take some time to look at the anatomical results. This was already known at year 1, that there were greater reductions in CST with faricimab dose Q8 weeks and PTI up to Q16 weeks versus aflibercept dosed at Q8 weeks.
We have a direct comparison between the faricimab Q 8-week arm and the aflibercept Q 8-week arm, and those comparisons in both studies favor the faricimab-treated arm. If we go to the next slide, we'll see that these greater reductions in CST in both faricimab arms were maintained through year 2 and that the anatomical results favor both arms of faricimab in the YOSEMITE and RHINE clinical trials. Next slide. We're gonna look at other secondary anatomical endpoints. Just a note that where you see an asterisk, there is a nominal p-value that's less than 0.05 when compared to aflibercept dosed every eight weeks. Here on this slide, we see that more patients achieved absence of DME with faricimab-dose Q 8 weeks or PTI up to Q 16 weeks compared to aflibercept through year two.
Again, I draw your attention to the dark blue lines comparing to aflibercept because those are Q8-week dosing arms for both drugs. Next slide. More patients achieved absence of intraretinal fluid with faricimab, either dosed Q8 weeks or PTI up to Q16 weeks compared to aflibercept through year 2. Next slide. Here we look at the rates of absence of subretinal fluid through year two, and they were high and comparable across all treatment arms. I have to say that DME is not really a disease of subretinal fluid. It is much more typically associated with intraretinal fluid. Next slide. Here we see the proportion of patients with a greater than or equal to two-step improvement in the diabetic retinopathy severity score. This is consistent across studies and treatment arms. We tend to learn from large clinical trials.
I think the teaching point here is that DRSS improvement is likely related more to VEGF than Ang-2 inhibition. Next slide. Now we'll look at safety. Faricimab was well-tolerated through the end of the study. Here we're looking at events per 100 patient years, and we see that ocular AEs and serious ocular AEs were well-balanced across the treatment arms when the data was pooled between the two studies, and that the confidence intervals are overlapping. Next slide. Inflammation, and retinal occlusive events have become critically important to clinicians understanding the safety of new molecular entities. Again, here on these tables, we see events listed per 100 patient years. I want to call out intraocular inflammation events. We see these rates are low, balanced across the treatment arms with overlapping confidence intervals.
The endophthalmitis events occurred in all three arms and were low, and infrequent. Retinal vasculitis and occlusive retinal vasculitis events were not seen in any of the treatment arms of either study. When we look at retinal occlusive events, these numbers were small in all arms of the study and were not associated with any inflammation. Next slide. In summary, over two years, faricimab demonstrated durable efficacy through disease control with up to Q16-week dosing. I think this really speaks to faricimab targeting two distinct disease pathways, which really lends credence to the thought that there is more vascular stability, more durable therapy, and that we're able to maintain long-term vision gains, at least through two years, as seen in these studies, because of targeting this second pathway.
When we look at the durable vision gains, the one-year BCVA gains were maintained through year two, but with less frequent dosing in the PTI arm. 78% of patients were dosed at Q12 weeks or Q16 weeks. When we look at the Q16-week dosing alone, it was 62% of patients. When we looked at anatomical outcomes, the initial improvements were maintained over two years. When we looked at key secondary analyses involving change in CST, absence of DME, or absence of intraretinal fluid, these results favored faricimab. Faricimab was well-tolerated, and importantly, there were no cases of retinal vasculitis or occlusive retinal vasculitis. There is a long-term extension study, the RHONE-X, that will continue to generate both efficacy and safety data through the next four years. If we now take the next slide, we will shift gears slightly.
Again, it's my pleasure to share with you the two-year outcomes from the phase III Archway trial, management of neovascular age-related macular degeneration using the Port Delivery System with ranibizumab. This was presented on Saturday at the Angiogenesis meeting by Charlie Wyckoff on behalf of the Archway investigators. I'm proud to say that I was one of the Archway investigators. Next slide. Again, it's important to begin with the Archway clinical trial design. It was designed to evaluate the efficacy and safety of continuous drug delivery with the Port Delivery System refilled every 24 weeks. Again, this is a first look at continuous drug delivery as opposed to the pulsatile drug delivery we have been experiencing with frequent injections.
In this study, there are just two arms, the Port Delivery System with 100 milligrams per mL of a special formulation of ranibizumab, compared to intravitreal ranibizumab injections given every four weeks, which has been the gold standard for more than 15 years. At screening, both arms of the study receive intravitreal ranibizumab injections, but at day one, the PDS arm receives the implant with the initial fill of drug. That drug is refilled at month 24, but the two visits prior to the refill are called supplemental visits, where patients are evaluated to see if they need supplemental ranibizumab injections. We'll be looking at these visits in the upcoming slides. Now, we already know that the primary endpoint was an average of the mean change in best-corrected visual acuity at weeks 36 and 40.
We already know from the reports in The Lancet that the PDS was non-inferior, and equivalent to monthly ranibizumab. But if we advance the slide, what we're going to present now is the end-of-study results going out to week 96, where patients would roll over to a port extension study. This extended follow-up gives us additional refill exchange procedures, and it gives us additional information on safety and additional information on the need for supplemental injections. We're going to look at key secondary endpoints through the second year, essentially, of the Archway study. Next slide. Again, the baseline demographics and ocular characteristics were well-balanced, and the average age of patients in Archway was around 75 or in the mid-70s. Importantly, patients had received on average five anti-VEGF injections prior to enrollment in the study. Next slide.
This is data that has been presented before. It shows that the PDS dosed every 24 weeks maintained vision through week 96. But here we're just showing the primary endpoint where the visual acuity results were found to be non-inferior and equivalent when averaged between weeks 36 and 40. There's one exception, and that's an expected transient post-surgical drop in vision, and this is real, and I do counsel and advise my patients that because it's a real surgery, they will have blurred vision for four to eight weeks until they recover. Then see that the lines are on top of each other. If we build the slide, you will see that these visual acuity results are maintained through week 96, and we have three additional refill exchange procedures. Next slide, please.
Per protocol, only non-inferiority and not clinical equivalence was assessed, and the PDS was found to be non-inferior to monthly ranibizumab when averaged over weeks 60 and 64 and averaged over weeks 88 and 92, and we see that the confidence intervals are overlapping. We also see that the difference in adjusted means at time points is less than one letter difference. Next slide, please. Let's look at anatomical outcomes. When we look at retinal thickness measured as the center point thickness, again measured from the ILM to the RPE through week 96, we see that these lines are essentially on top of each other and they include four refill exchange procedures. You may see that the lines begin to separate a bit between week 80 and week 96.
I'll just draw your attention to the vertical axis where it's measured in 50-micron increments. This difference is likely 20 microns or less, and as a clinician, that would not be significant to me or actionable to me. It's reassuring to recall the earlier slides that show that the visual acuity lines were essentially on top of each other with less than a letter difference at key endpoints. Next slide. Now look at the central subfield thickness measured from the ILM to Bruch's membrane through week 96. Again, we see through refill exchange procedures and out to week 96, these lines are essentially on top of each other. However, now we can see perhaps the separation at week 80-96. Again, this difference is small and is likely 20-25 microns or less.
As we think back to the visual acuity results we just reviewed, it makes us rethink the presence of fluid vis-à-vis visual acuity, that maybe control of disease through continuous therapy is as effective as maintaining vision despite these anatomical differences. Next slide. Now we're gonna talk about the supplemental treatments, and 95% of patients did not meet the supplemental treatment criteria. That criteria was a decrease of 15 letters from the best recorded BCVA in the study or an increase of greater than or equal to 150 microns in CST measured from the lowest CST measurement or a combination of both anatomy and vision, where an increase of 100 microns in CST was associated with a decrease of 10 letters or more in best corrected visual acuity.
Now we have 4 PDS treatment intervals to assess, and we see that the results are consistent through week 96, that essentially 95% of patients did not meet this retreatment criteria or supplemental treatment criteria, and vision and anatomy were able to be controlled. Next slide. Systemic safety of the PDS dose q24 weeks was generally comparable with monthly ranibizumab, as expected. Next slide, please. Now we're gonna look at ocular adverse events of special interest, and these are identified as adverse events of special interest because they emerged as we introduce a surgical procedure into the management of wet macular degeneration. What we'll find is that these adverse events of special interest in the PDS arm were well-characterized in the clinical trial setting and were generally manageable.
When we look at this table, we see that the number one adverse event was cataract, which is not surprising in this patient population. We also see adverse events in the PDS arm that we don't see in the intravitreal injection arm, such as conjunctival bleb or conjunctival filtering bleb leak. The rate of vitreous hemorrhage was small, and they generally cleared, not requiring vitrectomy surgery. We're now gonna talk about conjunctival erosions, conjunctival retractions, and endophthalmitis. Importantly, endophthalmitis occurred in 4 PDS patients and one monthly ranibizumab patient. The FDA has issued a boxed warning for the PDS because it has been associated with a threefold higher rate of endophthalmitis compared with monthly intravitreal injections of ranibizumab. Now, three cases of endophthalmitis were associated with conjunctival retraction that, in review of surgical videos, we could identify the root cause for the conjunctival retraction
This indicates that early detection and appropriate management with potentially surgical repair of conjunctival retractions or erosions could reduce the risk of endophthalmitis. Because of learnings from the Archway clinical trial, we can make recommendations for follow-up of these patients, again, using slit lamp examinations, perhaps a cobalt blue light and fluorescein stain, or serial longitudinal photographs of the conjunctiva overlying the implant to optimize patient outcomes. Next slide, please. In summary, the Port Delivery System refilled every 24 weeks, maintained vision and anatomic outcomes comparable with the gold standard for over 15 years, which is monthly ranibizumab injections. This has now been demonstrated through two years of follow-up in the phase III Archway clinical trial. What we saw was comparable vision and controlled retinal thickness through 96 weeks.
With the extended follow-up, we can see that the PDS was non-inferior to monthly ranibizumab for BCVA change at multiple points during the study. When we look at the durability of the Port Delivery System, we see greater than 95% of patients were able to go the full 24 weeks without requiring supplemental treatments with ranibizumab injection. When we look at the safety profile, it's one of the advantages of phase III clinical trials, is that you can have a well-characterized safety profile. Importantly, with extended follow-up, the safety profile was generally unchanged from the primary analysis, and no new safety signals emerged. The adverse events were generally manageable, but importantly, key learnings are being continually implemented to optimize patient outcomes.
Importantly, the PDS was associated with a threefold higher rate of endophthalmitis compared to monthly intravitreal injections, but meticulous implementation of the improved instructions for use with the PDS will be key for maximizing patient outcomes in the real world. I believe that is my last slide, and I would be happy to take any questions regarding both Vabysmo or Susvimo in the two-year data sets. Thank you for your attention.
Thanks, Nancy. We will now start the Q&A session. We have also currently, just to let you know, 185 people joining. The first question will come from Vimal Kapadia from Bernstein. Vimal, I will open your line.
Oh, great. Thanks, Bruno. Thanks, everybody for taking my questions. Just two, please. You mentioned that subretinal fluid is not a major issue in DME. Can I just ask how we should think about intraretinal fluid with respect to long-term outcomes in patients? Now, clearly, there's a benefit there for Vabysmo over Eylea. Based on the two-year data, would you argue this benefit has been proven, or could we actually see this benefit expand further beyond the two-year period? Then my second question, I appreciate it's not your data, but just given the debate on higher doses of, you know, anti-VEGF not driving differences in visual outcomes, I would appreciate your thoughts on the Eylea high dose trial data.
You know, at first glance, it seems like it's slightly better on BCVA, but it's more of a debate on drying capability. Just what are your thoughts on this data and how importantly, you know, keen to hear how you think Vabysmo stacks up against this high dose Eylea data. Thank you.
Sure. Nancy, maybe do you wanna take the intraretinal fluid question first, and then I'll take a stab at high dose.
Sure. I actually have a great interest in fluid compartment. Intraretinal fluid is damaging to vision, period. Whether it's an AMD or DME, intraretinal fluid is the real driver of visual acuity outcomes in my mind. I think it is critically important to understand that DME is an intraretinal fluid disease, and it is quite impactful that the anatomical results really favored faricimab when it comes to the absence of DME or the absence of intraretinal fluid. I think that this is a key finding from the YOSEMITE and RHINE clinical trials.
Thank you, Vimal. On the other data, a key point to note is really fundamentally this is where we're kind of different in our approach to unmet need. We actually think that the additional pathways is where we will get more benefit. The data that we've seen thus far.
From a phase II setting that didn't meet its primary endpoint, from what I understood. Yes, I think you're gonna see different agents with different impacts to CST. I think when we look at the totality of the data in phase III setting with Vabysmo, 3,200 patients showing consistent durability across the studies and the arms and the supportive CST and anatomic features, you know, we're really confident that this is a data set that stands up to scrutiny.
Great. Thank you.
Next question. The next question would come from Simon Baker from Redburn. Simon, I will open the line.
Thank you, Bruno. Thank you for hosting the event and taking my questions. Two, if I may, please. On YOSEMITE and RHINE and the PTI dose frequency, I was just wondering if there were any factors that led to Q 16 dosing interval other than baseline disease. If there were any other factors that were determining which patients were in that group. Secondly, a slightly broad question. You mentioned as one of the planks of Roche's ophthalmology development efforts gene therapy. I just wonder if you could bring us up to date with where you are there. As far as I know, the only project in ophthalmology that Spark have currently disclosed is in Stargardt disease.
I just wonder if you could tell us where we are there, given that was of course where Spark began its gene therapy efforts. Thanks so much.
Well, Chris, do you want to take the gene therapy, and then maybe we can discuss PTI after that?
Sure. Thanks for the question. I think broadly, as you will have seen in the announcement at the end of last year, we did have a gene therapy interest with 4D Molecular Therapeutics. We've terminated that relationship and wish the company good luck in the future. I think gene therapy remains a key platform of investigation for us within retinal conditions, and Spark remains very interested, and we're collaborating across our early research groups with Spark there. I can confidently say that we remain very interested in the potential for gene therapy to have an impactful contribution to therapies in the future for retinal diseases. No updates on any additional programs though as of today, but we remain very interested in the gene therapy platform. I think may-
Yeah.
Shall I just kind of take a stab at the YOSEMITE and RHINE factors leading to influencing the Q 16 and then maybe Nancy, I'll ask you to comment perhaps on the impact of that in real clinical practice. When we transitioned individuals from YOSEMITE and RHINE into the Q 16 arm, we actually took a number of factors in which included both assessments of visual acuity and retinal thickness over time. Patients can move upwards and downwards dependent on the state of their vision and the anatomical status of their retinas. That's...
These are the factors which clinicians use in the real world, and that's why, you know, as I say, as you see, we have this 80% are able to achieve Q8-Q12 or greater vision. But anatomy and vision were the main factors. I mean, Nancy, in terms of real world clinical practice, do you want to comment?
Sure, I'd be happy to. I can say in my own clinical practice, I have patients who are on a Q12-week dosing posology for their diabetic macular edema, and it's like clockwork. I have some patients who are on a Q16-week dosing posology, and they absolutely have to have their injections at those time points. In clinical practice, it's very hard for me to know what the underlying, either patient characteristics or ocular characteristics are that lend patients to these extended dosing intervals. This is really the advantage of having these incredibly large prospective clinical trials. I think that is a great question for a post hoc analysis to see what the patient profile is that does well with these extended dosing intervals with faricimab.
I think we have a lot more to learn from these large studies, and I look forward to those analyses.
Thank you very much.
Thanks, Nancy. Next one would be Sachin Jain from Bank of America.
Hi there. Thanks for taking my questions. It's a really simple one for Dr. Holekamp. I'm just trying to get a bit of a perspective on the clinical relevance of these assets. I wonder if you could just share with us your rough split of existing usage in AMD and DME, Lucentis, Susvimo, and Avastin, and just take a stab at how you think that shifts in the next two or three years with the introduction of Vabysmo, Susvimo. I just want to get a sense of how quickly you think that shift happens. Is it new patients or are there, you know, very frequent injectors or uncontrolled patients that are subject to a quick switch within the next, say, 6, 12 months? Thank you.
I'd be happy to take this one. I can tell you that I think the adoption of faricimab, of Vabysmo will be very, very rapid. It's an injection. It's easy for clinicians to reach into their refrigerators and pull out an injection. I think it will be a very quick adoption. I think patients will initially be switched because that's the model we saw when people switched from Lucentis to Eylea in the past. I can tell you that, again, I really like phase III clinical trial data because YOSEMITE and RHINE show us that, you know, like, almost 20% of patients will be dosed Q4 weeks or Q8 weeks. This is what gets me really excited about the PDS being a platform.
That Chris mentioned that hopefully soon we'll have the PDS for treating DME because I think even with Vabysmo, there will be a small percentage of patients, perhaps 20%, that might want the extended dosing durability of six months should the data prove good in phase III clinical trial. I think the uptake with Vabysmo will be very rapid based on the year two data. Again, I'm looking to the future for that small percentage of patients that still might want a different platform. Now, I'll turn to AMD. I am very excited about the Susvimo platform. In fact, I operated on three patients two weeks ago and implanted Susvimo, and they were very excited about it and looking forward to doing more. I think this uptake will be slower because it's a new surgical procedure.
I think the more physicians do, the more physicians will do, and that the uptake will accelerate as physicians get more experience with this new surgical procedure.
Did we answer your question, Sachin?
That's perfect. Thank you. I just wonder if I can push for any share assumptions in your own practice now and how do you think that shifts?
I can tell you that today, February 14, is the first day that I can buy Vabysmo from my provider, and I have placed an order for it, and I'm starting to get authorization for use. I am an early adopter and very much looking forward to it, but I was in the clinical trials. Again, I think other clinicians who weren't in the clinical trials, I think there will be an early adoption in DME because the data is so convincing, particularly the anatomical data. To summarize, I think Susvimo will have a slower uptake that will accelerate as more physicians get experience with this new surgical procedure.
Okay. Thank you for your time.
Thanks. Next question would be from Michael Leuchten, UBS.
Thanks, Bruno. Just a quick question for, I think, Dr. Holekamp, but maybe for Christopher. When we look at the PDS patients that are being treated today, how would you describe the characteristics? I'm assuming a surgical intervention is a bit of a tougher pitch to a patient than a straight-up injection. Maybe the three patients that you mentioned, Dr. Holekamp, like what's a typical patient that gets a PDS today, and how do you think they will develop over time?
Maybe a quick comment first, and then I'll pass to Nancy in terms of the clinical practice. I would say that as we've expressed over previous calls, that we continue to, and as Nancy's described, we continue to ensure that surgeons are trained very extensively because this is an important and new surgical technique for the Port Delivery System. The patient selection is an integral part. They have to be committed, and they have to be of the type whereby managing an implant is carefully considered. I think we have a two-pronged approach in terms of the training.
We have extensive case reviews, discussions, virtual reality simulators, and then we go on to in kind of peer-to-peer discussions to share how that training takes place, and to share direct experiences from case to case. I think that's really important. We will continue to learn how best to select these patients. Nancy, perhaps describe how you went through your three recent implants.
Well, I will say that these three patients, they were aged 81, 80, and 78 years old. They had all had multiple injections. They were quite enthusiastic about getting an implant. Now, when it comes to discussing the Susvimo implant, in this age group, two out of the three patients had already had cataract surgery, so they understood that they had a lens implant. This is a drug delivery implant. However, for each patient, I had special informed consent that included safety data from the clinical trial. I used not only standard surgical consent, but also special informed consent based on the data we learned from Archway.
Your question, you said, "Well, how would people, you know, balance a surgical procedure versus an intravitreal injection?" I have to say that we have routinely underestimated the anxiety and the burden that goes along with these injections. Patients are really quite enthusiastic about not going through that anymore, about having an indwelling long-term drug delivery system where it just gets refilled every six months. They are being told of the safety profile, and they're really still quite enthusiastic about it. Again, you know, when we say balancing injections to an implant, from our standpoint as a physician, I can tell you it seems like there's a big difference there, but we're underestimating the anxiety and discomfort that goes with those injections.
Thank you.
Did we answer all your questions, Michael?
Yep, that's great. Thank you.
Okay. Next in the row would be Peter Welford from Jefferies.
Hi. Thanks for taking my questions. Just taking this Susvimo for a minute, I wonder if you can just talk a little bit more about the monitoring you were talking about for the safety events. In particular, I guess what I'm trying to understand is the sort of burden, I guess, on the patient for that in terms of, does this require repeat visits? How many days, I guess, do you have to go back around, you know? How regularly does this require following up?
Just trying to get an assessment, I guess, of how, you know, how much we're actually reducing the visits or what the amount of monitoring that was required on a regular basis to reduce these side effects, particularly, I guess, at the moment as you know, experience grows. And then secondly, forgive me if this is an ignorant question, but just to understand, with Susvimo, would you immediately go ahead and do bilateral implants, or would you do one eye and then the other? How do you think about adoption of that drug or that med device in the case of patients in that case? And then secondly, just one for Roche. Just understanding the Port Delivery System longer term, with I think the DutaFabs, et cetera.
Can you just perhaps outline for us how predictable, I guess, once you have the phase I data, now you've got the PDS approved with Susvimo, how predictable can you be able to guess the pharmacokinetics, I guess, understand the future drugs, how, you know, how they could potentially fit in the PDS and the duration of dosing you've got? Or is it very much a case that for every drug, the PDS platform and how it applies and how the side effects, I guess, and frequency of dosing could very much differ from drug to drug, if that makes sense? Thank you.
Sure. Pam, so do you wanna go first, and then, Chris, you wanna follow up on the platform maybe?
Sure. I believe your first question was how am I gonna follow these patients? There are two key points. One is to follow the disease activity, and the other is to follow any safety signals. The data was so convincing that 95% of patients don't require supplemental injections that I really don't think that I need to follow patients for disease activity. I'm going to trust the data from the Archway clinical trial. Now, it's true, and you framed this question very, very well, that, you know, is this really gonna decrease the treatment burden? The Archway clinical trial actually had to see patients monthly, and so clinical trials aren't the practice of medicine. It will be up to physicians to decide how to follow patients from a safety perspective to look at the implant.
This, of course, will be done on an individualized basis. If the surgery was technically perfect and I don't see conjunctival retractions or erosions, and I'm very happy based on my past experience with the PDS that my Susvimo patient looks good, I will not really see them that frequently, but educate them to call me for redness, irritation, blurred vision, floaters, anything at all. But it's quite true. Clinical trials are not the practice of medicine, and physicians using Susvimo will likely determine the follow-up schedule based on an individualized approach. Now, I think your second question is, what do you think the uptake would be if people wanted bilateral Susvimo? We never do cataract surgery on the same day, so this won't be happening in quick succession.
I can tell you that a colleague of mine in Iowa who was in the clinical trials, his first Susvimo cases were actually on the fellow eye of patients from the clinical trial because they were so pleased with the PDS in the clinical trial that they wanted Susvimo in the fellow eye. Of two out of the three patients that I did two weeks ago are already asking about when they can have it in their other eye. I think if it's a successful treatment for patients, I think patients will be requesting it. The third patient I did, she had had a scleral buckle and evisceration in the past, and so she's not a fellow eye Susvimo candidate because those patients are outside of what was studied in the Archway clinical trial.
Some patients will be good candidates for bilateral Susvimo, and some patients won't be good candidates.
Thanks, doctor.
I think one of the elements of patient feedback which we keep getting from investigators around the world is that their patients in the clinical trials, such as Archway, do keep asking when can they have their second eye treated. Obviously, we have greater restrictions on active clinical trials, but that is an important area that patients have a desire for. In terms of the second question on the DutaFabs and potential new molecules within the Port Delivery System. I think what we look for in new molecules to go into the Port Delivery implant are those which are stable and can be concentrated at high molar concentrations.
I think the DutaFabs, as an example, are a great platform in themselves which are able to do that. As I said, we are potentially able to concentrate them at much higher concentrations than ranibizumab. So the answer to your question about how we can use the ranibizumab data to address how long these refills, you know, ultimately, your question is about how long can we go between refills with potential new therapeutics. I think we're still exploring. So I can't show any specific data, but what I can say is that I do believe it won't be incremental change that we'd be looking at as we look for new therapeutics in the Port Delivery implant.
I think the second element of that is, as we saw with faricimab going not an incremental improvement in durability, but a real step change in durability, you know, 75%-80% in the DME studies going to Q12 or more. It's difficult to model the impact of that for DutaFab within the Port Delivery System. So I do believe that that's something where we can't model, but we look forward to seeing the clinical data. But to take away is there are elements that we can model, but broadly, we'll be looking for a step change in durability for these patients. So exciting platform. Outside of the DutaFabs, yes, we will be looking at other molecular platforms which could potentially go into the Port Delivery System as well.
Peter, did we address all your questions? Yep. That's great. Thank you. Okay. We would have a final question, which comes from Christopher LoBianco. Christopher?
Hi. Can you hear me?
Yes.
Hi, this is Steve Scala from Cowen. Two questions. They're both market-oriented. First on PDS in the U.S., in what % of the addressable population is reimbursement set up with payers, since presumably there are drug and procedure components? And are there any intractable obstacles to setting this reimbursement up? We have heard that reimbursement or lack thereof has blunted the adoption of PDS so far. And then secondly, on faricimab, the incidence of serious AEs is very low, but it's still higher than Eylea. I imagine your competitor uses this as a competitive or counter detail. I'm curious what Roche's counter to that counter detail is, and if this isn't the competitor's assertion, what has been the competitor's pushback so far? Thank you.
Thank you, Christopher. A couple of points. On the Susvimo, as with all new products, we're going through all the reimbursement pieces and getting to permanent J-codes. Right now they're on temporary J-codes, but we don't see any unusual obstacles in the way towards getting to those. They obviously take a number of months to put into place, and that's the same for Vabysmo right now. Vabysmo will be having a temporary J-code, and then over the coming months, we'll be looking to transition to a more permanent J-code, which will obviously help practices. Most practices in the U.S. are adept at dealing with these temporary situations. That's happened for all previous launches as well, so they will be working through that.
Now, to your point on Vabysmo, to the clinical safety profile, I'll get Chris to comment or even Nancy further, but we've seen very few cases. These are very low numbers, so it's very difficult to talk about differences in the future. One thing we have done is looked at this, knowing the sensitivity of this in the community. We've looked at this very carefully, and we've been really transparent. We've been sharing the data since year one. You know, we share that data within a couple of months of having the data, and we'll be sharing the year two data. The way I would frame this is that we're very confident but not complacent, and we'll continue to look at this as we move forward.
As to what competitors are asserting about us, they will make many claims. I think we come back to the data. You know, 3,200 patients across four phase III studies and two indications simultaneously is where I think people will look. I don't know if Nancy or Chris have additional comments to add to that.
May-maybe one-
Oh.
Maybe one comment and then over to you, Nancy. I think as Nilesh said, we're extremely sensitive to this issue which I think you refer to by SAEs around inflammation. What we actually did is we looked at, with our reading center, at all the reported cases of inflammation. We went back and looked at the images, and there were, as Nancy highlighted, no cases of retinal vasculitis or occlusive retinitis across all of our programs as reported by physicians. I think we're not anticipating any surprises as we saw with other recently launched anti-VEGFs. Nancy, perhaps over to you.
Well, thank you, Chris. I was just gonna reiterate what you said. What we really care about are those cases of occlusive vasculitis because those are really untreatable and can result in severe vision loss, and they're really poorly understood. I don't see any of that in YOSEMITE or RHINE. You know, I appreciate that Roche has been very transparent because if you're not, it's only gonna show up later. You know, we all appreciate how transparent they have been and the extra effort to look in those cases. I am reassured that there are no cases of inflammation associated with retinal vasculitis or occlusive retinal vasculitis.
Okay. I would go on. We have two additional hands raised. The next one would go to Matthew Weston from Credit Suisse. Matthew?
Thank you, Bruno. It's a simple question for Dr. Holekamp, please. It follows on from Sachin's question about commercial uptake. I'd be very interested if you think that you and your colleagues have a warehouse of patients who may be poor responders to Eylea or who would, for various clinical reasons, you would be looking for new therapies as a source of patients to start faricimab on rapidly and whether or not we should expect essentially that warehouse to see very rapid uptake as soon as the drug is available. As clinicians evaluate how it's performed in that group, we can then see a more normal launch characteristic after that. I'd be very interested in that dynamic, please.
Sure. I'm happy to answer that. In fact, when this was discussed on the panel at Angiogenesis, I had my retina colleagues, including Jeff Heier, saying, "Yes, I'm going to use this. I have patients. I have a backlog of patients that I've been waiting to switch to a different drug with a different mechanism of action." I think we will see a rapid uptake, because we do have these patients. It is an injection and we start with switching. I think that we will see this rapid uptake. It will likely occur in patients for whom we know will get reimbursement, and the permanent J-code will certainly help with the uptake as soon as that is achieved.
Absolutely 100%, and I think my colleagues feel similarly that there will be a rapid uptake, and we will begin with switch patients, and we do have those in our clinic.
Dr. Holekamp, if I could push you. Can you give us any guesstimate of what proportion of your patients that is? Is that a mid-single digits number? Is it bigger than that? Is it a handful? I'd be very interested.
Oh, definitely more than a handful. When we talk about high VEGF need patients who need dosing every four weeks or every six weeks, that is, I would say somewhere between 10%-20% of the patients that I see. Those patients are absolutely looking for a treatment with a different mechanism of action that may help them decrease the treatment burden. I think we saw that in the PAT survey too, that we're looking for a different mechanism of action for a lot of our patients who still get frequent injections.
Many thanks, indeed.
The final question for today will go to Marietta Minets.
Yes. Thank you very much. Apologies. I actually typed my questions into the Q&A, so I suppose you didn't see them. I have one question for Nancy, just specifically on slide 57. The rate of cataracts looks increased. I was just wondering, I mean, is that just an artifact or is there actually a mechanism by which PDS can damage the lens, and how would that potentially evolve over time? Then just a couple sort of like market segmentation questions where I would obviously be interested in everybody's perspective. One is you said about 50% of patients in the real world don't make the 20/40 visual acuity.
I was just wondering, you know, if you look at the segmentation of those who don't make it, what proportion would you say are reasonably close to that and really incentivized to get there so they can drive? Or what proportion don't really care if they're a little bit above or below because they don't drive for other reasons? And what proportion are maybe sort of like so low that they also have an incentive to, you know, just really drive up their visual acuity just in order to be able to live a normal life? And the final question, if I can just sneak that in on Slide seven, I was just wondering why the survey participants did not seem to think that better drying agents are needed.
Is that because they actually think the existing agents are already so good at removing the retinal fluid, or is drying basically not considered as critical to the disease progress as we always thought? Thank you very much.
Right. That's quite a lot there. Maybe, Nancy, do you wanna take all the cataract question, and then Chris and I can follow up on some of the others?
Sure. The primary analysis, there was a numerical increase in cataract in the PDS arm compared to the monthly ranibizumab arm. I don't know if statistics were run to see if the numbers that we have at end of study are significantly different. You may not know this, but I've done cataract research in-depth for 20 years. The progression of cataract, it's a nuclear sclerotic cataract, is very common in people in their 70s. We expect to see both groups getting cataract. The difference between the PDS arm and the monthly ranibizumab arm, again, I don't know if it's statistically significant, but here's the key point. None of the cataracts were due to trauma from the drug implant, so none of them were traumatic cataracts. I think that maybe some statistics can be done.
Sometimes turning on the infusion line during the surgical procedure itself may cause some additional vitreous liquefaction. Vitreous liquefaction is associated with nuclear sclerotic cataract. I think the important point here is that none of them were due to trauma from the drug delivery implant.
Thanks, Nancy. Marietta, to respond to some of your other questions. I'll start with the ASRS data where the need for fluid was a little bit lower. I think this, in the way the question is posed, is what are your greatest needs? I think here you can see that durability of agents and new mechanism of action comes high. Obviously, those agents need to be able to show clinical benefit, and often that is supported by anatomic benefits consistently, and that is something we've seen in the studies outlined. To your question about 2040, I mean, interesting. I don't have all the segments that you mentioned. We look at this as really a place where as a threshold for vision that we'd love to achieve for many patients.
They often come in with much lower vision into the clinical trials, and if we get them to 20/40 or so, that's seen as quite successful. It's about 70-73 letters. Most countries around the world use that as a threshold for driving. We see it as a proxy for getting to success in a meaningful way. I think a lot of countries define that as also one of the features for independence of living, where people can get to the shops and do activities of daily living using the car. I hope that addresses your questions.
I was just wondering, you know, sort of if somebody sits below the... I mean, you know, if they can basically get reasonably close to 20/40 with their existing treatment, do they still have an incentive to actually switch to sort of like make that numerical threshold? Or do they say, "Well, you know, it doesn't really matter if I'm a little bit above or below." I mean, I'm just trying to understand, you know, how much inertia there might be in the market. You know, how many patients might be like, "Yeah, whatever, you know, I'll just, you know, stick with the treatment I've always had. Have longer dosing intervals than I really should.
Just accept that I'm not going to, you know, get the best possible outcome, but it doesn't really matter because in any case, I don't drive anymore, and I can't really read the papers. You know I just, you know, I can still, you know, I don't know, cook a cup of tea, and that's good enough for me.
Nancy, do you wanna make a comment on that?
Can I comment on that?
Yeah.
It's really interesting. I find that my patients across the spectrum of vision loss are highly motivated to protect and preserve as much vision as they can. I really don't divide it into, you know, patients getting to be 20/40. Everybody, if they understand what's at stake, which is really quality of life, every patient along that spectrum is motivated. I would just say that I wouldn't compartmentalize it like that. Patients are highly motivated to see better and see better with fewer injections.
That's great. Thank you so much.
Thank you. I think with that, we are at the end of our call. I would like to thank all the speakers again for their hard work and dedication to this field. I would also say thank you to the audience for your interest in Roche and emerging ophthalmology franchise, which we are building, and looking forward to provide you future updates and wishing you a good day. Bye-bye.