Ladies and gentlemen, welcome to Roche virtual event Update following ASH 2022. 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 on listen-only mode during the call. After the presentation, 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 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, 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, for the introduction. Can I have the first slide, please? Welcome to our last IR call for this year, where we would like to provide you an in-depth insight in our growing hematology franchise. Let me first quickly take you through today's agenda. We have several speakers with us joining. The first section will be with Peter Ahnesorg. Peter is our Franchise Head Hematology and Global Product Strategy. He will present our malignant and non-malignant hematology strategy and the overall portfolio. The second part goes to Charles Fuchs, our Global Head of Oncology and Hematology and Product Development. Charlie will take you through the key data presented at ASH 2022. Finally, we will close with a presentation from Gallia Levy, our...
The Chief Medical and Product Strategy Officer of Spark, and she will provide us an update on the SPK-8011 program. This is our gene therapy hemophilia A program. We will have roughly, I think, 60 minutes for the presentations, and we will have a 30 minutes Q&A session then following. Can I have the next slide, please? I also wanted to use this occasion here quickly just to sum up a bit and provide an outlook here for 2023. We had some trials which have shifted over into 2023, so 2023, again, is a very busy schedule. If you look here, in terms of the key readouts to come, it's, I think, I counted 18 readouts which we currently have scheduled.
What I wanted to highlight here is, I've highlighted a couple of them which we'll touch upon today. These are readouts, five readouts, late-stage readouts in hematology. You see them here colored in dark red. We have two studies for VENCLEXTA reading out, which are novel indications for this molecule in relapse refractory multiple myeloma and in first-line high risk and myelodysplastic syndrome. We have the readouts for crovalimab. This is our recycling C5 antibody which is dosed monthly subcutaneous in PNH. These are the COMMODORE 1 and 2 studies we are looking forward to. Also, I think here to highlight two CD20/CD3 studies. These are combination studies in second line DLBCL.
One is the STARGLO study, where we combine glofitamab with GemOx, and then the second study is mosunetuzumab with Polivy, the SUNMO study. These studies are actually scheduled for late 2023, early 2024, and this would be a big step forward here in terms of our CD20/CD3 program of taking the bispecifics into earlier lines of treatment. If I move on on this slide and just then cover the remaining oncology readouts, you see on the top we have a whole set of studies, neoa djuvant and adjuvant studies for Tecentriq reading out. Overall, in four indications, there is readouts for lung cancer, liver cancer, head and neck, and then later in the year in TNBC. You also see like two studies for tiragolumab and Tecentriq in combination.
Of course, everybody is watching the Sky 1 study, SKYSCRAPER-01 study here, first-line PD-L1 positive non-small cell lung cancer. Here, I just wanted to confirm the timelines we have previously communicated. We expect the interim OS data in Q1, and we will have roughly six months later, the final OS or towards mid of the year, early second half. If the interim passes and if the study will continue to the final readout, we will provide you with an update at one of the quarterly results calls. We have a second data set for tiragolumab and Tecentriq expected next year. This is in first-line esophageal cancer. This is the SKYSCRAPER-08 study. Just to remind you, this is a China-only study.
If we move down on the slide, you see we have an additional adjuvant study here in ALK-positive NSCLC for Alecensa reading out. This is the ALINA study. Outside of oncology, I think there's also several highlights here in neuroscience. We expect pivotal data from our phase III study, EMBARK, for our gene therapy in DMD. This is the study which is the basis for our filing in Europe and all the countries who reference to the Europe. It's also, I think, here important to keep in mind that our partner company, Sarepta, already is progressing with a filing in the United States and might even get approval as of next year.
This would also allow us, for example, to launch in some countries which reference to the United States, to have launches prepared. Two other, the two final studies I want to call out here is then the OCARINA study. This is our Ocrevus six-month subcutaneous home administration study, a PK/PD study, where we expect data middle of the year. This, I think, is also an important study as it would be a big step forward for our Ocrevus franchise and would allow us to go after roughly 20% of the current MS market. On the bottom, with TNKase, this is the enzyme tenecteplase. This is a molecule which is for a long time already in our portfolio.
Here we have a study reading out for patients who suffered from a stroke within a very narrow time window of four to 24 hours after the incident. If this study would be positive, would be a significant upside to this molecule, to TNKase, would probably double or even a bit more than double the potential for this molecule. This is just our update here on what is coming next year. We will remain very busy, and hopefully we are a bit more lucky than we have been in 2022 in terms of late-stage readouts. With that, actually, I would like to hand over to Peter Ahnesorg on the Roche Hematology strategy and providing an insight here on our overall pipeline. Peter, please.
Great. Thanks a lot, Bruno. I'm really excited to be here with all of you. My name is Peter Ahnesorg. I'm leading the hematology franchise in global product strategy. Over the next few minutes, I'll walk through broadly our hematology portfolio and how we are strategically thinking about it. Then, I'll pass it over to Charles Fuchs, our Global Head of Development for Oncology and Hematology, who will be able to share with you some of the data that was presented here at ASH. It's really timely to connect with you.
We had a pretty amazing ASH here in New Orleans, with lots of exciting data, and I think you'll agree with me, that we certainly have one of the broadest and deepest portfolios across both the non-malignant and malignant space in hematology. If you go to the next slide, this portfolio is obviously not by coincidence. It's really a result of a, of a very clear strategy. I just wanted to sort of elaborate a little bit on four points that I believe are very critical to our success in hematology here at Roche. The first one is really the balance in which we are investing both in areas of strength, like lymphoma, but also in new areas.
I would sort of point out multiple myeloma as an area where we have made significant efforts over the last couple of years to establish a very competitive portfolio. I think here at ASH, we've been able to start to demonstrate that we're on a really good path there. Also in the non-malignant heme space, we're making significant progress. Charlie will be able to share some of the pivotal data that we were able to present at ASH on crovalimab. Next to that, I think it's really important to appreciate that more and more a success factor in hematology becomes the ability to build combinations, and across many of the disease areas, we have a portfolio that allows us to really build novel combinations.
Specifically, we're excited about polatuzumab, Polivy, in lymphoma as a combination partner to our bispecifics. I'll spend a little bit of time later on talking about the costimulatory molecules because we're really industry leaders here in a very exciting area of building powerful combinations for patients suffering from lymphomas. Beyond just these bispecific molecules, we're also quite focused on diversifying our pipeline into different modalities. We're very honored to be joined by Gallia Levy here today, who's the Chief Medical Officer at Spark. Who'll be able to speak to you later on about our progress in gene therapy. As you probably saw, we also made a quite important strategic partnership earlier this year with Poseida Therapeutics.
I'll spend a couple minutes later on to speak about why we believe the Poseida allogeneic CAR-T platform is quite unique and will really enable us to broaden our approaches across different hematologic disorders. Lastly, you probably have seen this consistently as you've been following us. We're also quite focused on improving patient and provider experience, ranging from, you know, four-weekly subcutaneous administration in PNH, which we think is going to be a true convenience benefit for patients, all the way to fixed-duration treatments for patients suffering from malignant hematologic disorders, where we believe this can really make a difference both for patients as well as for healthcare systems.
If we go to the next slide, and before I head into sort of more of the specifics of the portfolio, I just wanted to reiterate that we believe in significant growth of the hematology market over the next five years. And if you look at this chart and you will appreciate that, specifically in areas of tremendous growth, like large cell lymphoma, CLL, multiple myeloma, we have built a quite comprehensive and competitive portfolio that we believe will enable us to continue to be leaders across the heme space. On the next slide, I wanted to double down on the concept of bispecific antibodies.
We have invested a lot of energy over the last decade in building first-in-class capabilities of antibody engineering, now we're reaping the results. Obviously, we've proven with Hemlibra and in collaboration with our colleagues at Chugai that a bispecific antibody can really revolutionize the treatment of a disorder like hemophilia A. Now we're also seeing that in malignant hematology. This year, we had the approval of Lunsumio in third line plus follicular lymphoma. I think as you're all aware, we actually decided to progress with two CD20, CD3 bispecific antibodies, because we really believe that these molecules are differentiated based on their engineering, that translates in different opportunities for providers and patients.
I will speak a little bit more about that as we dig deep into the different disease areas. As a first disease area, if we move forward two slides, I'd love to speak a bit about non-Hodgkin's lymphoma and start really with large cell lymphoma here. As I think you all know, patients in large cell lymphoma can be cured with R-CHOP, it's also pretty apparent and well established that roughly 40% of patients are not cured. More progress is needed here.
With the POLARIX study that explored exchanging vincristine for polatuzumab, Polivy, we, for the first time in 20 years, have delivered a positive study that established that really using Polivy in this setting is an advance over using R-CHOP. Why is that relevant? Well, it's relevant because we know that if patients progress after first-line therapy, options are limited. In fact, beyond first-line therapy, there's really only two options, probably, CAR-T and transplant that are truly curative. Both of these options come with a certain mortality and certainly significant morbidity. Also, these treatments for patients that relapse come with significant financial toxicity.
As you can appreciate here on the right side of the slide, there's been several external analyses now of the immense burden of cost that happens when patients recur. We believe with Polivy, we really are introducing a solution that offers more patients in the frontline setting an opportunity for cure. Certainly, we've established that exchanging vincristine for Polivy improves the possibility for patients to enjoy a longer relapse-free survival in that setting by roughly 27%. If we go to the next slide, based on these exciting results, we're now seeing approvals all across the world. In fact, the map you see on the left side here is already outdated.
We have more than 50 countries that have approved the POLARIX regimen by now. We're making progress day by day, gaining reimbursement. In the countries where it is already reimbursed and available, like Germany and Japan, we're seeing significant uptake and very positive feedback from providers. We are super encouraged by this launch. As I'm sure you're all aware, we're currently in conversations with the FDA and have a PDUFA date of, in early April next year. We are very excited to bring this option also to patients in the United States. Beyond Polivy, on the next slide, I already mentioned the two bispecifics we have in lymphoma.
As you see the data mature, also some of the data we presented here at ASH that Charlie will go through with you in a couple of minutes, really underscores that these two molecules are differentiated, and they address different needs for patients and providers. With Lunsumio, we not only have the first CD20, CD3 bispecific antibody approved in Europe, and we believe approval in the United States is imminent. Our PDUFA date is just before the new year. We also see that this molecule really is suitable for outpatient and community delivery and particularly well-suited for treating patients that have indolent diseases or that are not able to tolerate intensive therapy. On the flip side, there clearly is a need for intensive therapy.
You all know that CAR-T therapy is well established by now, we believe with glofitamab, we've developed a molecule that really has a chance to see eye to eye with CAR-T therapy, suitable for aggressive, particularly aggressive large cell lymphoma. You probably also saw if you followed ASH that we presented some pretty exciting data in mantle cell lymphoma, which is another really aggressive disease. We've gotten a lot of really positive feedback from treaters of mantle cell lymphoma on the promise that we're showing there. If we go to the next slide, I just wanted to deep dive a little bit in where we are with Lunsumio.
As I mentioned, it's approved, and we're quite excited that next year or maybe in early 2024, depending on sort of how events stack up, we'll be seeing randomized phase III data in combination. Lunsumio, we believe, is a molecule that is very easily combined with other agents, we're excited to see data in combination with lenalidomide in follicular lymphoma and in combination with Polivy in large cell lymphoma. We believe that these combinations are really a, an opportunity to move Lunsumio to earlier lines of therapy and make the benefits available to more and more patients broadly.
If you go to the next slide, and deep diving a little bit more on glofitamab, as you probably saw, we published in The New England Journal of Medicine, over the weekend, concurrent with the presentation here at ASH, that glofitamab is a really active molecule, in diffuse large B-cell lymphoma.
We've submitted that data to both EMA and FDA, and we'll be working with regulatory authorities to get approval hopefully next year. Also in the timeframe of next year, again, maybe based on events early 2024, we'll be seeing the STARGLO data, which really will be the first randomized data set in diffuse large B-cell lymphoma, establishing what these bispecifics in combination with chemotherapy can really do for patients that have a very aggressive type of lymphoma. We're also combining glofitamab with these costimulatory molecules. I'll speak about that in a couple of minutes.
Lastly, we're also very excited to announce and had an opportunity here at ASH to also announce that to our investigators that we'll be taking glofitamab to the frontline setting in a phase III study really looking at glofitamab in combination with Polivy and R-CHP. Building on the POLARIX regimen, we believe this will be a very attractive study for both patients and investigators as you'll be able to get the best available regimen in the frontline setting and then an opportunity to add a bispecific which we believe is really going to increase the chances for cure for patients suffering from this aggressive form of lymphoma.
On the next slide, I just wanted to point out another feature of glofitamab that we believe is really important, and that's the convenience aspect. glofitamab is both given as a fixed duration regimen, and it has a very simple dosing schedule, as you can appreciate here from the slide, that minimizes the time that patients need to spend in the clinic. We believe that this makes glofitamab very competitive as a choice in large cell lymphoma. As Charlie will go into in a bit more depth, we're also very encouraged and presented data here at ASH that patients who actually achieve a response with glofitamab have durable responses, and these responses persist beyond stopping the treatment with glofitamab.
These patients really go into durable remissions, and you don't need continuous treatment with glofitamab to maintain these remissions, which we believe is a really strong value proposition for patients, and one that we're very excited to bring to patients hopefully next year. On the next slide, I wanted to change gears a little bit. I promised, I guess, twice now, to talk about the costimulatory molecules. These we believe are very differentiated and quite unique to our portfolio. They also speak to our ability to engineer these bispecific antibodies. The concept here is one that we learned from CAR-T.
If you understand what's happened with the generation of CAR T technology, it's that the very first generation of these that was just based on the T-cell receptor was actually not very effective and quickly sort of needed to be revamped. The current generation of autologous CAR Ts that you see in lymphoma are actually all cells that were engineered to have a dual signal, both for the T-cell receptor as well as a costimulatory receptor. What our antibody engineers have done is to basically mimic that in a molecule. We'll be able to use glofitamab as sort of the T-cell engaging therapy. We have a molecule that binds CD19 and the costimulatory receptor 4-1BB that would basically then give you your second signal.
We have some very exciting, sort of emerging T-cell data. You can see one example here on the right side of the slide, that suggests that this approach will really enable us to get more responses off sort of what we're seeing with glofitamab. As I just mentioned, glofitamab gets you into very durable long remissions. If you can increase the number of patients who are getting into these remissions, we believe, this will be a very potent combination. On the next slide, I just wanted to also highlight that we have two approaches here in parallel. Not only CD19, 4-1BB, but also CD19, CD28. We're exploring both of them in parallel as combination partners for glofitamab at the moment in phase I studies.
We're very encouraged by both of these molecules and see quite differentiated activity. lots of excitement there and, you know, hopefully more hope for cure for these patients suffering from aggressive lymphomas. Changing gears now, I wanted to move to myeloid malignancies. On the next slide, this is probably not a surprise to you know, we're focusing quite a bit on multiple myeloma because we believe there's still significant unmet need in this area. If anything, this has been underscored by many conversations I've been able to have here at ASH. Over the past couple of years, we've now built a competitive portfolio in multiple myeloma.
We have venetoclax that we're studying in the CANOVA study together with our partners at AbbVie. We originally, I know, communicated that we might even be able to see data from the CANOVA study by now. Events are unpredictable, they are taking longer. We haven't been able to unblind the CANOVA study thus far. We're really looking forward to do that in the beginning of next year because we believe that venetoclax in a selected multiple myeloma population of patients that have the t(11;14) relocation translocation will make a tremendous difference. This would be the first targeted therapy for multiple myeloma, and we're very excited to bring that forward. In addition, we have two bispecific antibodies.
I'll talk a little bit more about the two of them in a subsequent slide. I mentioned earlier on that we believe in the power of combinations. We feel these two molecules offer a unique ability to combine. Lastly, the front-runner asset in our partnership with Poseida Therapeutics is the BCMA-targeted allogeneic CAR-T, and we're quite excited to move that forward. I also have a slide to get a little bit deeper into that. On the next slide, I first wanted to focus just a little bit more on VENCLEXTA. As you know, we've been very successful with VENCLEXTA. We're approaching roughly $2 billion probably in this year in terms of overall revenue.
This is driven, as you know, from the CLL and AML settings where VENCLEXTA is established by now. Moving forward, next year we're going to see data from not only multiple myeloma, as I just mentioned, but also MDS in the VERONA study. We believe that not only these sort of new phase III data points reading out, but also additional progress we're making in AML and CLL will contribute to significant growth for VENCLEXTA over the next couple of years. On the next slide, I wanted to spend a minute just sort of telling the story of the two bispecifics we have in multiple myeloma. We have cevostamab, which targets FcRH5. It's actually the only molecule in multiple myeloma that has this target.
We have some really good data that shows that targeting FcRH5 is a very potent way to address multiple myeloma. We're excited to move this program forward. It's currently in phase I dose finding, we will be hopefully able to communicate next year more on what next steps will look like with cevostamab. On the other side, we have a bispecific molecule that has a two-to-one format that targets GPRC5D. This actually now also has a WHO name. It's called forimtamig. Forimtamig, we believe, has best-in-class opportunity to target GPRC5D.
We know there are other molecules out there that have that target, but we also believe that these molecules have limitations in terms of their ability to really address a broad patient population because of the safety challenges that are being seen with this class. Forimtamig is a bispecific antibody that has been very thoughtfully designed to overcome some of these limitations. We believe this has a best-in-class potential. Again, we're in phase I dose finding right now and look forward to next steps next year. On the next slide, I wanted to talk about the CAR-T platform from Poseida. As I already mentioned, we believe this is a quite differentiated platform.
We believe that allogeneic CAR-Ts are going to be critical in the future because of the limitations that we're seeing to the manufacturing of autologous CAR-Ts and the high demand for this type of modality, particularly as it moves to early lines of therapy and the potential to cure patients. Poseida has established a really strong mechanisms of manufacturing these cells. We believe in the scalability of their process. We're also really excited about the product, which has a highest in industry level of T-cell T stem cell memory cells. These types of T cells, we believe are prone to persist much longer than other T-cell populations.
We believe this sets this product up for more durability as compared to competing products. As I mentioned, we're moving this forward predominantly in multiple myeloma, where we already have a phase I ongoing. We're quite encouraged by the first dose levels in that study. We'll hopefully be able to share more updates with you and the scientific community next year. We're also moving forward a CD19, CD20 dual CAR for lymphomas that we believe is going to be very differentiated. We have a couple of other assets and are particularly excited also to combine our capabilities in antibody engineering with the Poseida platform to generate additional products for hematologic disorders.
On the next slide, I just briefly wanted to touch on another aspect of antibody engineering and bispecific technology. As you probably are aware, one of the limitations of sort of the first generation of bispecific antibodies is that you need a cell surface target, which limits the diseases that you can address with these types of antibodies. So what our engineers have been able to do is to actually engineer a bispecific antibody that is able to bind peptides on expressed on MHC-1 complexes on the surface of cells, and thereby targeting sort of intracellular proteins that are being displayed.
Our front-runner program in that space is a WT1 by CD3 bispecific antibody that we believe can make a big difference in AML. We have some very encouraging preclinical data, some of which you can see here on the right side of the slide that gives us confidence that this molecule is active, so we're moving it forward in the clinic, and are quite excited to hopefully also bring bispecific technology to AML, which as you may know, is another area across hematology that has significant remaining unmet need, and would benefit from additional treatment options.
Changing gears now, and moving towards the end of my presentation, I would obviously be remiss to talk about our non-malignant hematology portfolio, and the standout here obviously is Hemlibra. On the next slide, you know, we had another really amazing year with Hemlibra. It's the number one prophylaxis treatment in the U.S. and in Europe. We're seeing, you know, north of 60% non-inhibitor share in some European countries, and, you know, believe there is still significant room for growth in the markets where Hemlibra is already established. We're also currently in communication with EMA about the mild to moderate label expansion based on the HAVEN 6 study.
Here at ASH, we've been able to share data on HAVEN 7, which Charlie will talk a bit more, which really kind of underscores the opportunity to start prophylactic treatment early in babies. You know, underscores the difference that Hemlibra can make even in very early pediatric treatment. In the rest of world, we also believe there is significant growth opportunity for Hemlibra. We're still sort of getting reimbursement in more and more countries, particularly for the non-inhibitor population. Are excited to see more and more patients getting access to Hemlibra as we progress into the next year.
On the next slide, I just wanted to touch, sort of briefly on the bar that Hemlibra is setting for the treatment of hemophilia A. It's clearly, as a prophylactic treatment, way superior to factor VIII, and patients are highly satisfied with treatment by Hemlibra. Many of them are choosing to use it in more infrequent dosing intervals. Hemlibra by now has a very well-characterized safety profile, of more than 18,000 patients, treated globally and seven-year follow-up data. We believe the bar for new molecules to come into this space is very high. We also believe that just incrementally improving factor is not going to be the solution.
I think, if there is innovation beyond Hemlibra by bispecific antibodies, it would need to demonstrate normalization to really have significant benefit for patients. We also believe that new treatment options would need to really demonstrate head-to-head with Hemlibra that they are superior and that they have a safety profile that offers the same confidence to patients as Hemlibra does. You'll hear from my friend at Spark, Gallia Levy, the Chief Medical Officer there, about our gene therapy, because we do believe that for patients who do not want to choose prophylactic treatment, gene therapy in the future might become a really interesting choice, and we're certainly very encouraged by the data that our colleagues at Spark are producing in this area.
Last but not least, on my last slide, really want to talk about crovalimab. This ASH has been the big coming out. We were able to present the first phase III data on crovalimab, which, as you know, is an anti-C5 monoclonal antibody that has recycling capabilities, which allows for a very low dose, very low volume administration, that enables a monthly dosing at home, subcutaneous, which we believe, despite the fact that there are many treatment options for patients suffering from PNH, is something that is very differentiated. For these patients who have to have frequent visits to the clinic to get infusions so far, this is going to be a very liberating choice.
We're quite excited about the potential that the COMMODORE 3 study offers for us to bring this to China. There's really very limited treatment options currently for PNH patients in China and a significant patient population. The COMMODORE 3 dataset has allowed us to actually already submit this in China, and we're looking forward to regulatory approval and reimbursement hopefully next year. Beyond that, we have a very comprehensive clinical development program for crovalimab, not only in PNH and aHUS, but also in sickle cell disease, where we started two studies this year looking both at the acute as well as the chronic population. We believe there is significant lifecycle opportunity for crovalimab beyond just the first sort of C5 indications in PNH and aHUS.
With that, I'm very happy to pass the baton on to my colleague, Dr. Charlie Fuchs, who's the Global Head of Oncology and Hematology Product Development here at Roche. Charlie, over to you.
Peter, thank you for that terrific review of our strategy across hematology, and it's great to be here today.
As you point out, this year's ASH Meeting put on display the extraordinary breadth and depth of our portfolio with high-profile presentations across a gamut of hematologic malignancies and rare blood disorders. While I won't be able to cover all of those presentations, in this meeting, I would like to share with you some key studies highlighting the work in non-Hodgkin's lymphoma, multiple myeloma, hemophilia, and paroxysmal nocturnal hemoglobinuria. I also want to point out that, beyond today's speakers, we're also joined today by Marion Ott, our Global Franchise Head for Myeloid Malignancies and Multiple Myeloma, Ginna Laport, our Global Franchise Head for Lymphoma and CLL, and John Pasi, our Global Franchise Head for Rare Blood Disorders. Marion, Ginna, and John will be available to answer your questions during the Q&A portion of our meeting.
If, turning to the next slide. You know, Genentech and Roche have a extraordinary legacy in transforming the landscape of non-Hodgkin's lymphoma from the first introduction of Rituxan to the advances presented at this week's ASH Meeting. As you'll see on the next slide, Peter outlined the fact that although R-CHOP transformed the care, the first-line therapy of large cell lymphoma, that despite the clear benefit of R-CHOP, there remained an unmet need in the first-line treatment with approximately 40% of patients experiencing relapse or just refractory to frontline therapy. At last year's ASH, as you know, we first reported the results of the POLARIX trial comparing pola-R-CHP, which in which Polivy, our CD79B antibody drug conjugate, replaced vincristine.
These results, as you're aware, proved to be the first positive trial in the first-line therapy of large cell lymphoma in more than 20 years. Last week at ASH, we reported continued follow-up on the POLARIX trial. With more than three years of median follow-up, patients treated with Polivy plus R-CHOP continue to show a statistically significant reduction in the risk of disease progression or death. Moreover, no new safety signals were identified in the longer follow-up analysis. As Peter mentioned, pola- R-CHP is now emerging as a new standard of care across the globe with health authority approvals in 56 countries, including the EU, the United Kingdom, Japan, Germany, Canada, and others. We're working currently toward approval in the U.S. with, as Peter mentioned, a PDUFA date in April of 2023.
Turning next to our CD20, CD3 bispecifics, we presented updated results from our pivotal phase II trial of Lunsumio monotherapy in patients with relapse refractory follicular lymphoma. At ASH 2021, this trial reported a 60% complete response rate and a 78% overall objective response in patients with heavily pretreated relapse refractory follicular lymphoma. This compares quite favorably to the 14% historic complete response rate seen in this setting. With longer follow-up at this year's ASH Meeting, we reported that the majority of responding patients remain in remission after two years with a 24-month duration of complete response of 63%. Of note, therapy was delivered entirely in the outpatient setting with a very manageable CRS profile, which was almost entirely low grade. Additionally, on the next slide, we compared the Lunsumio response to that of the patient's last prior therapy.
As we reported last week, the duration of complete response associated with Lunsumio was markedly longer than their immediate prior therapy, with the majority of patients treated with Lunsumio remaining in remission after two years. Moreover, as seen in the right panel, progression-free survival associated with Lunsumio was double compared with the progression-free survival for patients on their last prior therapy. As you're aware, in oncology, response to therapy steadily declines with each subsequent line of therapy. As such, this marked improvement in tumor response with Lunsumio as compared to their prior therapy, documents the impressive efficacy of this molecule. In sum, Lunsumio represents an important new treatment option as a first-in-class, off-the-shelf, fixed duration, outpatient therapy for these patients. As Peter mentioned, Lunsumio is now approved in the EU, and we eagerly await the imminent approval in the U.S. in the next coming weeks.
Sorry, my lights went out. We're using green technology. Well, I suppose you can see me in the dark. Turning next to our other CD20, CD3 bispecific glofitamab, which leverages a unique two-to-one format of CD20 to CD3. At this year's ASCO meeting, we reported the data for fixed duration Glofit monotherapy in heavily pretreated relapse refractory DLBCL with a complete response rate of 39%, including a similar response rate among patients who had progressed after CAR-T therapy. At this week's ASH Meeting, we shared updated data demonstrating that 12 months after the end of treatment with fixed-duration glofitamab, the majority of patients remained in remission after the cessation of therapy. Moreover, two patients who had progressive disease after achieving a CR returned to CR following retreatment with glofitamab.
We were very pleased that in conjunction with these data presented at ASH, there was a simultaneous publication of our data this week in The New England Journal of Medicine. As Peter mentioned, these data have been submitted to both the EMA and FDA, and we await the results of those ongoing reviews. Beyond relapse refractory DLBCL, we also provided updated data for glofit monotherapy in relapse refractory mantle cell lymphoma, a highly aggressive, difficult-to-treat lymphoma, especially after a BTK inhibitor. As we shared, following a BTK inhibitor, glofit monotherapy conferred an 84% objective response and a 73% complete response rate. Based on these very promising data, we will be launching a phase III trial in relapse refractory mantle cell lymphoma.
At this week's ASH, on the next slide, we presented updated data evaluating glofitamab in combination with R-CHOP in high-risk, previously untreated diffuse large B-cell lymphoma. Of note, in this trial, the majority of patients had stage four disease, 75% had extranodal disease, and a third had bulky disease with masses greater than 10 cm. Nonetheless, glofitamab plus R-CHOP induced early and high response rates with very low CRS rates. The majority of these high-risk patients achieved a complete metabolic response, and 93% achieved an overall response. Additionally, CRS events were all low-grade, grade one or two, and occurred in only 10% of patients. The requirement for cycle one hospitalization was removed entirely from the protocol.
As Peter mentioned, on the basis of these and other results, we will be launching a global phase III trial of glofitamab with the POLARIX regimen in the first-line therapy of DLBCL. Turning next, further building on the data for glofitamab, we shared data from our dose escalation trial for the combination of glofitamab plus our CD19 4-1BB ligand bispecific in relapse refractory non-Hodgkin's lymphoma. In this heavily pretreated patient population, this combination demonstrated a 49% complete response rate in aggressive non-Hodgkin's lymphoma, which was heavily pretreated, and a 65% complete response rate in indolent lymphoma. As further documented, rather, on the waterfall plot, the response across the range of escalating doses of therapy is quite impressive. Additionally, the combination has a very manageable safety profile.
We look forward to continuing study of this chemotherapy-free combination that leverages the signal one effect of glofitamab and the co-stimulatory features combined that really mimic CAR-T therapy in an off-the-shelf, easily accessible format. As Peter mentioned, we continue to build on our growing portfolio of novel therapies for multiple myeloma, which now includes VENCLEXTA for patients with 11-14 translocations, our two bispecific molecules, and our allogeneic BCMA CAR-T therapy being developed in collaboration with Poseida Therapeutics. This week, on the next slide, we presented updated results from our phase I dose escalation trial of cevostamab in relapse refractory multiple myeloma. Patients on this trial were heavily pretreated, having received a median of six prior lines of therapy, and 85% were triple class refractory.
At last year's ASH, we reported that among patients who received this unique bispecific at a target dose of 132 mg or higher, the objective response rate in this heavily pretreated, highly refractory patient population was 57%, with 33% of patients experiencing a VGPR or better. At this year's ASH, we reported on the duration of response, showing the durability among patients who completed the planned 17 cycles of therapy, finding that 17% of patients remain in response without progression, with a median of 10 months following completion of cevostamab. Based on these results, cevostamab appears to be a unique new efficacious treatment option. This is the only FcRH5 targeted agent and therefore, beyond monotherapy, offers the potential to combine with other agents, including BCMA-targeted therapies.
Also at this year's ASH, we share the results of our dose escalation study of our GPRC5D CD3 bispecific in relapsed refractory multiple myeloma, which included patients who had previously received CAR-T and other bispecifics. As shown, we are seeing similar activity for both the IV and subcutaneous formulations, with an objective response rate reaching 71% and very manageable CRS events. Given this very promising activity and tolerability for monotherapy, we are moving forward with both monotherapy and combination studies for this molecule. Finally, I want to conclude my discussion with our growing portfolio in non-malignant hematology. As Peter outlined, Hemlibra has transformed the treatment landscape for people living with hemophilia A. There remains an unmet need in infants, young boys with severe hemophilia A.
In routine practice, infants do not receive prophylaxis owing to the challenges of delivering one to three intravenous injections of factor per week, requiring typically central venous catheters. However, Hemlibra, which is approved for infants, enables initiation of prophylaxis at the time of diagnosis through subcutaneous administration, thereby mitigating the potential serious bleeding events in infancy, including intracranial hemorrhages. HAVEN 7, which we presented at ASH, is a multicenter open label, single-arm study of Hemlibra in boys under the age of 12 months with severe hemophilia A. Turning to the next slide, as reported this week, among these young boys treated with Hemlibra, 78% had zero bleeds requiring treatment. There were no spontaneous bleeds that required treatment, no muscle bleeds requiring treatment, and no intracranial bleeds. Those bleeds that required treatment were exclusively traumatic.
These interim results from HAVEN 7 demonstrate that Hemlibra achieved meaningful bleeding control with a favorable safety profile in infants with severe hemophilia A. Moreover, overall, the composite data from the HAVEN clinical program across the gamut of patient populations with hemophilia A continue to reinforce the safety and efficacy of Hemlibra and its potential to redefine the standard of care for people living with all severities of hemophilia A. Finally, turning to the next slide, at this year's ASH, we presented data on crovalimab, our anti-C5 antibody, using recycling technology that enables rapid and sustained complement inhibition as well as monthly subcutaneous dosing. COMMODORE 3 is a single-arm phase III trial conducted in China evaluating crovalimab in people with PNH in China who had not been treated previously with complement inhibitors. I should point out that in China there is no available complement therapy for paroxysmal nocturnal hemoglobinuria.
As shown, the trial met both its co-primary endpoints of hemolysis control with a marked reduction of LDH and transfusion avoidance. This is an important result since without treatment with a C5 inhibitor, median survival is five years. With a C5 inhibitor, life expectancy in this population is essentially normal. Based on these data, we are moving forward with a China first filing while we await the results of our other global phase III trials, COMMODORE 1 and 2. We are actively studying crovalimab in other diseases where complement inhibition may be important, including sickle cell disease and atypical hemolytic uremic syndrome. Thank you for the opportunity to share our results from ASH. Now I want to turn it over to Gallia Levy, the Spark CMO, to review with you the data from the SPK-8011 program. Gallia?
Thank you very much, Charlie. It's fantastic to see all the progress in the hematology pipeline. As mentioned, I'm the Chief Medical and Product Strategy Officer at Spark Therapeutics, and I will talk to you today about our data on SPARK 8011, our gene therapy for hemophilia A. If we go to the next slide. Before I launch into data, I just wanna talk a little bit about what we are looking for in a successful gene therapy, as well as Spark's approach to hemophilia A gene therapy. We are really anchoring on what we call the four pillars that we believe are necessary for a successful gene therapy. Safety, efficacy, predictability, and durability. The approach that Spark has taken to try to achieve these four pillars is highlighted on the slide.
One is to use the lowest effective dose. This has always been the goal at Spark to target expression within a therapeutic range using the lowest effective dose to minimize liver toxicity and risk of anti-capsid immune response. We also know from literature that HCC risk correlates with increased dose in animal studies. What you can see on the right is a schematic of the doses being used in hemophilia A clinical trials. You have our four doses you'll see on the next slide for Spark SPK-8011 on the left compared to the doses being used in other hemophilia A clinical trials. It's not obvious when you look at the way gene therapy dosing is described, but the Spark AD11 doses are between, you know, 2.5 to... Oh, sorry. Previous slide.
2.5 to 120 x lower than other doses being investigated. In addition, we believe it's important to ensure durable factor VIII expression. We've always believed this is possible in hemophilia A, that there shouldn't be a difference really between hemophilia A and hemophilia B in this respect. Hemophilia B has demonstrated now up to probably more like 10 years factor nine expression in those early trials. Also in hemophilia A dogs, there's been no decline in expression up to 10 years. Though there have been unexpected declines in expression observed in other programs, we've always believed that it's possible to achieve durability. Then predictability, and what do I mean by this? This is what is a patient going to be told that they can expect to get from a gene therapy.
It's a one-time treatment. There's no chance at this time to get another one. We believe it's important that patients have a sense of what they are likely to achieve. To that end, we are aiming to deliver the optimal dose and immunomodulatory regimen. Next slide. This is our trial design. You see the eligibility criteria on the left. They're pretty standard for hemophilia A trials, and we've tested four doses ranging from 5e 11 to 2e 12 vg per kilo. Our last dose is 1.5 e 12 vg per kilo. You see the numbers of patients that we've treated now.
We've evaluated several different immunomodulatory approaches, our trial objectives were quite standard, evaluating safety and efficacy, as well as the extent and durability of factor VIII expression. Next slide. These are the data that we're really excited about from this trial. As I mentioned, we always believed it was possible to achieve durable factor VIII activity in hemophilia A, and that is what we sought to do. We believe that our data demonstrate that we've now done that. What you see is the majority of participants maintain factor VIII expression within the mild hemophilia range. You see here the data from 16 participants who have data going more longer than a year.
It's the same data on the left in the table and on the right in the graphical format, essentially showing that over more than one year, two, three, four, and in the cases of two patients, five years for the first two, we have durable factor VIII expression, with the majority being in the mild hemophilia range. Then, overall, in the whole data set of 23 patients, we have sustained expression of factor VIII in 21 of those 23 with several methods of immunomodulation. We've only had two patients that have lost completely lost factor VIII expression. Those were in the very early days of the program, and they've been reported on before. Since that time, all patients newly enrolled have maintained factor VIII expression. Next slide, please. Here you see the bleed data.
The ABRs, annual bleed rates for the participants on the trial. You see on the left, the pre-infusion annual bleed rates, and on the right, the post-infusion annual bleed rates for the same individuals. With the blue being the traumatic bleeds, and the dark blue being the traumatic bleeds and light blue being spontaneous bleeds. Really, the ones we really look at are the spontaneous bleeds. You can see for all types of bleeds, there was a significant decrease. Significant reduction in ABR, 82% for people that were on prior prophylaxis and 99% for people that were on prior on demand. Clearly these factor VIII levels that we're seeing expressed in these patients are translating to decreased bleeding, which is obviously fantastic to see. Next slide.
Our safety profile. Always important to mention the safety. We have seen quite a nice safety profile in Spark AD11. No fatalities, no factor VIII inhibitor development, and no thrombotic events reported. We've seen adverse events similar to what is seen for other systemic gene therapies, LFT elevations that we believe are related to a capsid immune response. They have been mild for the most part, and all were transient, asymptomatic, and resolved with steroid treatment. There was one that was considered an SAE. That's because the patient was brought in for elective steroid administration, and we've previously reported on that. There's been no further SAEs since that report.
I do believe it's important to talk about the AEs related to immunomodulatory agents. We have seen this. This is for the most part related to the use of oral steroids, which we showed in our separate poster that often leads to long steroid usage and may lead to adverse events. This is something that we've decided that we would like to move away from, and that's why we're exploring different immunomodulatory regimens and anticipate a better safety profile with respect to these steroid-related adverse events. Regardless, they were all mild to moderate and all resolved except hypertension and headache and nausea and stomach pain in one patient. Next slide. In conclusion, we really are anchoring on these four pillars: safety, efficacy, durability and predictability.
We aim to achieve these four pillars in a hemophilia A gene therapy. We have demonstrated durable factor VIII expression with the majority of participants expressing levels in the mild hemophilia A range up to five years. 82%-99% in bleed rates and substantial reductions in factor VIII consumption. No major safety signals. We have some transient ALT increases which are, you know, at the timing of a expected capsid immune response but have been easy to manage. We are currently continuing our investigations to overcome the challenge of AAV-mediated gene transfer and the anti-capsid immune response to further reduce variability in factor VIII expression that's getting at that predictability pillar. We have obviously an ongoing evaluation of our phase I/ II study data with continued commitment to achieve these four pillars.
I suspect there is a lot of curiosity as to timing for next steps, we look forward to providing our next update early next year. With that, I will thank you for your time, I'll pass it back to Bruno.
Thanks a lot, Gallia, for this update on our gene therapy efforts at Spark. With that, we would open the Q&A session with our three speakers and also our three additional panelists. The first question would come from Richard Vosser from JP Morgan. Richard, please.
Hi. Thanks for taking my questions. Hopefully you can hear me. Maybe two questions. Firstly, just on crovalimab. Just thinking about the commercial opportunity and how you see it. The data in China, and I admit it's China data, and we haven't seen Soliris in China, to my knowledge. The transfusion avoidance, when you look cross-trial, looks a little bit lower than Soliris. How do you think about that as we think about the other COMMODORE trials and the commercial positioning if that is true? Also your thoughts on the factor B data as well. Iptacopan has shown superiority at ASH in C5 refractory patients, so how are you thinking about how that all fits together? Then maybe just 1 question on the Hemlibra and... Sorry, excuse me.
On Hemlibra and, BIVV 001. Admittedly Hemlibra is way better, but factor VIII is gonna get an upgrade. Just your thoughts on how that changes your ability to switch patients over to Hemlibra for the growth going forward. Thanks very much.
Okay. I chip in and answer this. I think the first thing we were talking about was crovalimab and the treatment avoidance, and the figure that we got, which was around 51%. I think it's really important to note that the patients coming into the C3 study in China were quite different from the historic studies which you mentioned, where there was a significant number of patients who weren't so treatment, transfusion dependent. In fact, in the study that was undertaken in China, the C3, there wasn't a single patient who was not treatment, transfusion dependent. That is, everybody was dependent on transfusion. We had a much more significantly dependent population. We had a population with much more aplastic anemia and myelodysplastic syndrome and a population with much longer diagnostic time.
We have a much more severe population that we're looking at. I think we need to bear that in mind when we try and compare data across trials. The second point you mentioned is about factor B. They're clearly very interesting data, particularly refractory patients. I think we would all welcome to hear more data and particularly in naive patients about how this might work. Clearly the mechanism of action is somewhat different in that it's higher up the complement cascade and that could have its own implications. I think a number of unanswered questions, but anything that brings new treatments to the patient forum is clearly something that we're all very excited to hear more about. The third question I think was about Hemlibra and BIVV001.
Clearly, as you say, yes, factor VIII gets an upgrade with BIVV001. I think Hemlibra is a drug that's well established. It's proven its effectiveness. Its bleed rates are really low. It's simple to use. We wouldn't really expect to see patients moving back from Hemlibra onto BIVV001 on the basis of how we see the real world data and how patients report to us. I hope that's helped answer your questions.
Thanks very much.
Next questions would come from Michael Leuchten, UBS. Michael.
Thanks, Bruno. Three questions if I could, please. One, just for my understanding on Mosun. I get that the CRSs that we've seen are, we have seen are low grade, but in the community, how are they dealt with? How do patients get managed when epilogue three CRS happens? That's question number one. Question number two. Talquetamab, Johnson & Johnson's GPRC5 x CD3, looked decent, maybe a touch better than yours from an efficacy, but certainly from a CRS perspective. Just wondered if you could comment on how you think you can maybe manage that safety side of things going forward. You talked about monotherapy and combination. On 8011, Gallia, just going back to what you said at the very end.
How are you thinking you're gonna be able to manage the suppression of the immune system to allow easy administration? You went through that quite quickly. I just wondered if you could give a little bit more color on that. Thank you.
Hi, this is Ginna Laport. I'll take the first question. I'm the franchise head for lymphoma and CLL at Roche. For Mosun, on how the low-grade CRS can be managed in the community, at our launch, we are planning a very broad and deep physician education. As you know, low-grade CRS is usually manifested by a fever and the physicians, their sites and the patients will be educated on how to identify fever, when to call the patient. I'm sorry, when to call the physician. Most of these community sites, as you know, have infusion chairs, and with a fever, it's really, it's clinical judgment on what to do next. You know, we are confident with the broad education and support that this should be able to be managed very appropriately.
I will take the AD11 question, so thank you for the question. Yeah, I mean, taking a step back about two years ago, we looked at, you know, all of the data that we had on oral steroids with prophylactic oral steroids, reactive oral steroids, and decided that that was not the way, right? We decided to take some time to step back, follow the science, really try to figure this out. We've put some different immunomodulatory regimens in our trial since that time. It's premature to talk about the specific results from those, but we're really encouraged that we found a better way forward.
We answered all your question, Michael?
There was one about the, you know, your side effect profile on compared to the change J program on the CRS.
Marion, can you get your audio to work?
Yes. I'm lots of problems with the voiceover. Dr. Kusuma from GPRC5D . For inventory in those escalations, are we able to say here, making any comparisons, various demos and we also will have GPRC5D sub-q.
I think we have here some technical issues.
Marion, we're having trouble hearing you. I can chime in while you're working on your audio, Marion. Just that, you know, obviously the data we showed at ASH for our molecule is early in dose escalation, both for IV and sub-q. As Peter mentioned, during his presentation, we actually have reason to believe that the toxicity profile for our molecule, you know, will be a value proposition in terms of managing both CRS and the skin toxicity, which is important with this molecule, particularly for patients who are going through the experience. You know, I think we see potential for this molecule, which has, you know, in dose cancellation is at this point having reasonable response rates approaching 71% or higher.
What we think is, you know, very good, toxicity profile. More to follow as we continue to advance this program.
Thank you.
Thanks, Charlie. We would move on. The next questions would come from Tim Anderson with research. Tim.
Yes. Thank you. A couple of questions, if I could. On slide 10, you talk about bispecifics in a first-line setting. You mentioned glofitamab, but you also, in that same slide, talk about these costimulatory molecules. Both of those are, you know, quite early. My question is, what would be the realistic timeframe to move those into a frontline combo setting? I would have to imagine that's, you know, several years away yet. The second question on Hemlibra. You mentioned 36% patient share U.S. and Europe, so, you know, factors are still the predominant therapy, essentially the other 60% of the market. Where do you think that 36% can go to over time? Do you think that can, kind of, flip it around and maybe ultimately become something like 60% of the market? Thank you.
Hi, this is Ginna Laport again. I can take the first question on the use of bispecifics in the first line setting. As Peter mentioned, we are planning a large phase III trial in the first line setting with Glofit combined with our POLARIX regimen of R-CHP and Polivy, and we anticipate first patient in later this year. As far as Glofit combined with the costimulatory molecules, those programs are still earlier in development, are in dose finding. speaking about those, the use of that combination in the first line setting is a bit premature right now, really depends on over the next year, the results we see when those, when and if those will go to first line. Our highest priority now is the Glofit plus the POLARIX regimen.
Thank you.
Yeah, thanks, Ginna. Maybe I can speak about the question with the sort of the opportunity in the non-inhibitor population. I mean, well pointed out, Tim, right? I think we're seeing actually that the average across countries is really an average that comes from very different sort of realities in different markets. We have markets in Europe, for example, that have more than 60% share in the non-inhibitor population, which kind of speaks to the opportunity. We remain very optimistic that there is significant room still to grow based on significant numbers of patients who, you know, are bleeding and will really benefit from prophylaxis.
We're seeing, you know, a significant proportion of the market being more, more conservative, and sort of looking at the evolution of Hemlibra and with the, you know, long follow-up data, we now have the established safety profile. We believe that there is a significant opportunity for us to increase share in the non-inhibitor population, which will sort of result in growth over the next several years.
Thank you. Tim, did we answer all your questions?
Yes. Well, actually, if I can just ask one more. When there is apprehension to use Hemlibra, you know, in favor of factors, you know, what's the driver of that apprehension? You talk about certain markets, penetration being 60%, why wouldn't it be that high in, you know, all markets?
Yeah, great question, Tim. Well, I think it's multifactorial, right? I would, one, point out that there are economic factors in markets that are driving behavior, right? Economic factors that are different between infusing versus giving a subcutaneous solution. Then as I said, I think there's also, you know, patients who have a very long experience with factor and have been sort of apprehensive in changing to something new and have sort of been, you know, waiting to see how things will pan out for other patients on Hemlibra. We're seeing more and more of those switching, right, based on the increasing sort of data set and comfort, and also positive patient experience that we're reporting on Hemlibra.
Thank you.
Thanks, Peter. Before we move on in the queue, I would maybe take one question from the Q&A section, which comes from Rob Lim. It's a broad question, so maybe Peter, you can start. It's about, can you elaborate how you see the NHL bispecific market competitive landscape evolving with regards to other CD20 bispecifics that are in late-stage development and how it will compete against CAR-Ts, so outpatient versus hospitalization requirements, et cetera?
Yeah, no, I mean, you know, we are very confident that we're in a very good position here with CD20/CD3 bispecifics. We don't believe that one size will fit all. We do actually see significant differentiation between Lunsumio and glofitamab, and we believe that that will drive preference and provider behavior. Lastly, you know, just to double down on what I said in my presentation, we also believe that a fixed duration of therapy is an incredibly strong value proposition as compared to having to treat patients forever, right, and not knowing if you actually achieved a durable response or, you know, if you're dependent on just receiving the treatment over and over again.
You know, I feel very good on that. With regards to CAR-T, you know, I think there will always be a space for CAR-T. That's why we also decided to partner with Poseida. I also believe that's going to be a limited number of patients that really will be great candidates for that. Hopefully we can cure these patients, right, and that'd be amazing, and we're definitely committed to be a part of that. Then there is going to be a lot of patients that will not be well served with CAR-T, where bispecifics will really make a difference.
Particularly as we think about sort of the early, you know, the early line settings, we believe that bispecifics have a much better, and particularly, you know, our bispecifics, Lunsumio and glofitamab, have a much better value proposition, as compared to CAR-T therapy.
Mm-hmm. Thanks, Peter. The next question would come from Steven Scala from Cowen. Steven, please.
Thank you. I have several questions all revolving around Venclexta's ultimate potential. To what extent do safety issues limit its use today? Do you expect any potential competitors now in development to differentiate on efficacy and/or safety? Third, early on in its launch, AbbVie estimated Venclexta's potential at $6 billion in 2025. Without being specific, at the time, it seemed Roche thought the potential was maybe half that, but the trend certainly suggests AbbVie's correct. How are you thinking about Venclexta's potential now? Just to be clear, when will you file crovalimab in the United States? Thank you.
Hi, this is Ginna Laport. I can take the first Venclexta question. As you know, with Venclexta, we currently have a trial with the CRISTALLO, which we anticipate finishing later this year, which is Venclexta plus Gazyva for the first-line fit population. We have Venclexta/Gazyva approved for the first-line unfit from CLL14. Expecting that the results are positive with CRISTALLO, you know, we will be, we hope to be approved for a more fit population. We also have Venclexta in the second line after the MURANO trial. Going with how will Venclexta, how will these second-generation BCL-2 inhibitors differentiate? We don't know yet. We think the data's too early. As far as safety, Venclexta, you know, I know you're referring to the tumor lysis syndrome, how that's managed.
As far as we know with our, the second-generation competitors, they also are tackling this TLS ramp-up and the scheduling. As far as the data we've seen so far, it does not look differentiated from VENCLEXTA. Obviously we have the first-mover advantage, and I think we just need to wait and see with these second-generation BCL-2 inhibitors.
Mm-hmm.
Yeah, I'm building on top. Thanks, Ginna. In terms of the overall potential, I mean, I'm, I can't comment on specific numbers. As I mentioned during the presentation, we're going to be around about $2 billion finishing 2022. Really strong growth trajectory. You know, we are adding a significant number of new indications in the next couple of years. I mean, I mentioned MDS and multiple myeloma, and there is still an ongoing, you know, development program that will lead to more indications. You know, where that is ultimately going to take Venclexta, I'm not going to speculate on, but we're definitely very happy about the collaboration and the trajectory here.
Thanks for the question on Crovalimab. As we mentioned, we're going to read out the non-China studies, COMMODORE 1 and 2 in 2023. We're going to look at the datasets, you know, COMMODORE 1, 2, 3, and then, you know, submit the totality of that data to health authorities all across the world. It's too early to speculate what the timelines for that are going to look like. You know, we're definitely going to update you all once we read out the data and obviously are, as always, committed to presenting that at upcoming scientific conferences.
Mm-hmm. Thank you.
Thanks, Ginna and Peter. Next question would come from Richard Parkes. Richard?
Hi. Thanks, Bruno. Thanks for taking my question. Firstly, on the multiple myeloma bispecifics. Obviously with the CD20 bispecifics, it's taken quite a while to get through clinical development, given, you know, you've had to learn around dosing and management of the CRS. I'm just wondering whether that, you're confident those learnings have put you in a better place to accelerate growth of, accelerate development of the multiple myeloma programs going forward. The second part to that is just, you mentioned BCMA combinations in multiple myeloma. Is it possible to combine two CD3 bispecifics in one combination safely? I just, I don't know whether that's possible or not. Second question, just on Hemlibra. I don't know if this is probably for John.
I remember when Hemlibra launched, speaking to physicians, and the feedback was happy to switch patients to Hemlibra, but those patients that want an active lifestyle, maybe encourage them to stay on factor VIII because you don't get full normalization of factor VIII levels and it's obviously, is that benefit that ALTUVIIIO offers with BIVV001. Is it fair to assume that those patients are probably still have remained on factor VIII rather than switch to Hemlibra, so kind of naturally protects you from competition from BIVV001? Is there a pool of patients out there that are taking Hemlibra and then maybe topping up when they want to play sports at the weekend? Thank you.
I can. Let me just. Marion, is your audio working?
Yeah.
Not quite yet. Well, I can take the bispecific question. You know, with regard to the learnings that we've had really across all our CD3 bispecific programs, I think we're in a very good place to accelerate all of these new programs. Namely, I think we've really learned a lot in terms of how we can use tocilizumab, how we can do step-up dosing, how we can, you know, obviously look at both IV and sub-Q formulations. And with all of that, I think we're applying it to accelerating the programs with multiple myeloma. And, you know, to your question about can you combine, that is an active series of studies we're doing now.
You know, that includes looking at our current portfolio of multiple myeloma bispecifics with BCMA bispecifics. you know, beyond that, I think, you know, given our work with Poseida, you know, considering how we might integrate that with off-the-shelf cellular therapy. I think, I think we learned a lot over the years. I think we're now in a very good position to accelerate across indications, using these technologies. John, did you want to take the next part?
Yeah, no, I will do. Thank you. The question is really about patients and men, boys who do a lot of sport and are very active. Clearly you're right. Some people are playing sport three times a week, in which case they'd be very much of the mindset that they would want to be normalized. They were a group that, as you suggested, who haven't moved over to Hemlibra as such. There is a degree of activity there. We talk about active patients, and it can be from somebody who does something three times a week, four times a week, to somebody who does something less intensive, less frequently.
That's a group of patients who could benefit from Hemlibra and perhaps could move to it because the understanding that we've got now about its effectiveness, how much background activity you need to prevent bleeding, how when you stop bleeding, your target joints settle down and all those sorts of things, I think that can play into a changing dynamic. Physicians are also becoming much more comfortable with using this as a drug. It is a novel therapy. It was a novel therapy, and everybody had a degree of anxiety. That's all melting away. The results speak for themselves in real world data. There will be a group of patients who will identify that they definitely need high levels at particular times of the week.
If we think about other therapies, there will be a decline, and they won't necessarily work for everybody. What I tend to feel is that the activity question depends on what you actually mean by activity. Do you mean somebody who's doing an awful lot of sports or not so much? I think there is a move in clinical practice to get more patients on because the convenience aspect, the low bleeding rates actually go hand in hand to make life and quality of life that much better.
Thank you.
Thanks, John. With that, we move on. The next one in the row would be Peter Welford from Jefferies. Peter?
Hi. Thanks for taking my questions. I've got three, hopefully brief. Firstly, just on glofitamab, I wonder if you can update us on the state of the U.S. filing and when that could be accepted. I guess more specifically, as you mentioned in the remarks, we got the data really that could potentially lead to a filing last ASH. It's almost one year ago now. What was it, I guess, that you've been waiting for to supplement the dossier that led to the fact that, you know, now almost one year later, we're still waiting for the FDA to accept the glofitamab filing. Secondly, Roche has a history of looking at in-house combinations and priding yourselves on that, as we can see in the lymphoma portfolio, for example.
In multiple myeloma, obviously CD38 is well-entrenched, probably is the mainstay standard of care at this point. Any thoughts on whether or not Roche should have a CD38 in its pipeline, or are you very happy just to partner and do trials on top of that standard of care? Thirdly, briefly, I think probably for Galli, just with regards to phase III, I'm not going to ask when it's going to start, but just curious what you have or what thoughts you have in terms of what do you think regulators in a pivotal study for particularly FDA want to see in terms of patients in the phase III, how long do those patients need to be studied before FDA potentially is going to be comfortable to accept a filing based on a phase III program?
Thank you.
Hello, this is Ginna Laport. I'm happy to take the questions on glofitamab. The glofitamab BLA was filed with the FDA in early Q4 this year. You're correct that it was the top-line results were presented ASCO six months ago. The agency requested longer follow-up data for survival. To respond to their request, we waited before submitting until the data was a little bit more mature.
you know, with regard to your question about our assets with CD38, you're absolutely right. We don't have a CD38, although we are looking at combinations with these bispecifics. Namely, it's the data for monotherapy in highly refractory settings. The activity has been impressive as well as the tolerability. We know that the real value of these molecules is in earlier settings and in combinations. We are looking at a variety of combinations I mentioned earlier with other bispecifics, but also with, you know, other standards of care, including anti-CD38 molecules. Albeit we don't have an anti-CD38, we have access to them.
We see looking at we, you know, we think those partnerships, with these other molecules is gonna have a great impact in moving these things into the routine earlier therapy of multiple myeloma.
Should I take the AD11 question?
Yes, please. Mm-hmm.
Yeah. Thanks for the question. I think, you know, I think the answer to that question is probably different for different products, right? Every gene therapy is different, we know that FDA has requested longer-term data in the past for others. I believe in that scenario, there was a significant difference between the phase I/II data and the phase I/II program and the phase III program. We believe that our phase I/II data really stands out, our durability really holds up in phase I/II, we anticipate, you know, really being able to leverage those data. It's obviously all premature until the conversations happen with health authorities and, you know, obviously dependent on the phase III data as well.
Mm-hmm. Thanks, Gallia. Then we would have the final questions for today coming from Charlie Mabbutt from Bernstein. Charlie.
Hi. Thanks, Bruno. Firstly, on hemophilia again. Physicians we've spoken to there still seem to be a fair amount of skepticism on patients taking gene therapy, particularly in hemophilia A, when you have Hemlibra available. I guess, what are your thoughts there, and what do you think you actually need to see in the data to start to change those opinions? Secondly, on crovalimab, I presume the focus in China is there first up because there's not really any available. I guess, how are you thinking about the competitive positioning in the rest of the world where C5 inhibitors are better ingrained, particularly in the U.S.? Considering the issue of sort of the drug-target drug complexes you've seen when you switch from other C5 therapies in those patients. Thanks very much.
Yeah. You know, you are right? Gene therapy in hemophilia A is early, right? We think the current options leave a lot to be desired, and that's why we're very excited about AD11, right? We think once we read out pivotal data for that option, that will be very different to what's on the table today and will change the landscape. In terms of who is going to, you know, be looking at that, I agree with you. I think the vast majority of Hemlibra patients are not going to be interested in gene therapy, right? Because they're interested in a prophylactic treatment. We think the patients who are going to be interested in gene therapy are the patients who don't want to get prophylaxis.
We believe there is a patient population out there that is looking for that. You know, it'll be really interesting to see, as gene therapy options improve how these patients are going to be choosing this option. Also, I mean, in the near term, right, how many of them are actually going to make a decision today versus waiting until, right, better options come around. I'll pass it to John for the C5 question.
Yeah. Thank you. I mean, the question is really about how does it stack up against more established C5 therapies. I think one of the big things that stands out for crova is the fact that it's subcutaneously administered once a month. At the moment, we're looking at alternative C5 therapies that are given every two weeks or every eight weeks, or maybe they're given every eight weeks subcutaneously, but that still requires a hospital visit. It could change the treatment burden significantly by being able to self-administer something once a month. I think that's a really important component. The other thing that you mentioned was drug antibody complexes. That is a self-limiting phenomenon which wears out after a number of weeks as we swap over.
We don't see that that's going to stand in its way in differentiating once you're established and you can gain the benefits from the fact that it's subcutaneously administered. I hope that helps.
Thanks, John. I think with that, we are now at the end of our call on hematology. I would like to thank all the speakers and the panelists for all the dedication and the time they put into the preparation. I would also like to thank Loren Kalm and Anita, from the IR team, who were involved in setting up the presentations and preparing the speakers. Also our back office, who was involved in organizing everything. With that, I would like to wish you just a peaceful holiday season with your beloved ones. I'm very much looking forward to meeting many of you again in 2023. Bye.
Happy holidays.
Thanks everybody.
Thank you. Happy holidays.