Good morning. This is Tim Power from Bristol Myers Squibb, Investor Relations. Welcome to our Investor Event at ASCO 2023. We're presenting important data across our hematology and oncology portfolios this week. It's exciting news for patients and a lot to discuss today. I'm joined for today's discussion by Samit Hirawat, our Chief Medical Officer, by Adam Lenkowsky, our Chief Commercialization Officer. Samit and Adam will go through our slide presentation, followed by Q&A. At the end, I'll also be joined by two of our cell therapy leaders, Lynelle Hoch, Senior Vice President, Cell Therapy Franchise Lead, Rosanna Ricafort, Vice President, Cell Therapy Clinical Development Lead. We go to Slide 2. On this slide, I'll refer you to a forward-looking statement. With that, I'll hand over to Samit to begin the presentation on this slide.
Thank you, Tim. Good morning, everyone. ASCO is a very important meeting for BMS, and this year we are excited to share updates spanning both hematologic disease and solid tumor malignancies. Later this month, we will also present important hematology data at both EHA and ICML congresses. Turning to Slide 4. What did we show at ASCO? First, our COMMANDS study data shows that Reblozyl is superior to ESAs in the first-line treatment of patients with transfusion-dependent, low-risk MDS-associated anemia. For the first time in over 30 years, there is a new option for patients, and Reblozyl has the opportunity to become a new standard of care in frontline treatment for this disease. We are also making great progress in cell therapy, advancing multiple programs across our portfolio.
Breyanzi has the potential to expand into new indications like chronic lymphocytic leukemia. Our TRANSCEND CLL study is the first and only pivotal multi-center trial where a CAR T-cell therapy has shown improvement in efficacy and durability in this patient population with considerable unmet medical needs. We also look forward to presenting new Breyanzi data at ICML in additional indications, including follicular lymphoma and mantle cell lymphoma. We saw real-world data from Myeloma CAR T Consortium, which further strengthens Abecma's profile and reinforces prescribers' confidence outside the clinical trial setting. We are also excited about our emerging CAR T targeting GPRC5D in relapsed and refractory multiple myeloma.
We have seen new data for Opdivo across both hematology and oncology, with the SWOG Cooperative Group presenting improved PFS using Opdivo versus the current standard of care, brentuximab vedotin, on top of a chemo backbone in first-line advanced Hodgkin's lymphoma. Finally, we are progressing our research in lung cancer, reinforcing the long-term benefits seen with three-year follow-up. In the neoadjuvant data from study CheckMate -816 and four-year updated data in the first-line metastatic setting with CheckMate -9LA. We have also shown that repotrectinib provides a durable clinical benefit in patients with ROS1-positive non-small cell lung cancer, including those with CNS metastases, which is very meaningful. As we know, CNS involvement leads to poorer outcomes. We received priority review status in the U.S. with a PDUFA date of November 27th and look forward to a potential approval later this year.
Taken together, this shows the breadth and the depth of our development programs across hematology, cell therapy, and oncology. Let's begin with our phase III COMMANDS study data for Reblozyl on Slide 5. We know there remains a high unmet need for patients with transfusion-dependent, lower-risk MDS-associated anemia, who need treatments that effectively address chronic anemia better than ESAs with a more durable response. Chronic anemia and dependence on blood transfusions leads to a greater than 50% increased mortality in these patients, with a median survival rate of less than five years. COMMANDS is a randomized head-to-head trial of Reblozyl versus ESAs in the first-line treatment of patients who are ESA-naive.
The study enrolled an all-comer patient population of RS-positive and RS-negative, with a composite primary endpoint of red cell transfusions, independence for at least 12 weeks, with a concurrent increase in mean hemoglobin of at least 1.5 g/dL . Looking at COMMANDS study results on Slide 6. Reblozyl showed superiority over ESAs, with twice as many patients in the Reblozyl arm achieving the primary endpoint. In addition to the overall intent to treat benefit, Reblozyl also showed benefits across subgroups regardless of EPO levels, transfusion burden, and common mutations like SF3B1. As you can see on the right side of the slide, Reblozyl also delivered more durable responses, with median transfusion independence of nearly 2.5 years, one year longer than those receiving ESAs. Turning to Slide 7, we are looking at RS subgroups.
An important objective of treatment is to both achieve transfusion independence and, even more importantly, sustain it. You can clearly see longer durational response in both subgroups, including in RS-negative, where the median has not yet been reached. Moving on Slide 8, we see that Reblozyl had a manageable and predictable safety profile that is consistent with what was seen in previous clinical studies. On Slide 9, you see the ongoing studies which are part of the Reblozyl development plan. INDEPENDENCE is a phase III trial in the first-line treatment of patients with transfusion-dependent myelofibrosis-associated anemia, who are also receiving a JAK inhibitor. This trial is currently accruing, and we anticipate data to read out in 2025. The second trial is an ex-U.S. phase II study in patients with both transfusion and non-transfusion dependent alpha thalassemia. Data is also anticipated in 2025.
Lastly, we will initiate the phase III ELEMENTS trial later this year in first-line, non-transfusion, dependent, lower-risk MDS-associated anemia. Shifting now to cell therapy on Slide 10. Later today, we will be presenting our TRANSCEND CLL data for Breyanzi in patients with relapsed or refractory CLL or SLL, whose disease has progressed on a BTK inhibitor. The study also explored a subgroup of patients, which we call the primary efficacy analysis set, who, in addition to progressing on a BTKI, have disease that has also failed venetoclax. This is a patient population with a significant unmet medical need, as there are no other approved treatments or established standard of care once both BTKI and venetoclax treatment options have been exhausted. Patients have poor outcomes with other available therapies, with very low complete response rates and duration of response of less than six months.
The primary endpoint of TRANSCEND CLL was complete response rate, key secondary endpoints included overall response rate and MRD. On Slide 11, you see the efficacy in the subset of patients included in the primary efficacy analysis set. The study met the primary endpoint with a complete response rate of 18.4%, with a median duration of response of over 35 months and the upper bound not yet reached. In this heavily pre-treated, high-risk population, this is a very encouraging outcome. It means that Breyanzi is the first CD19 CAR T to demonstrate a benefit in a pivotal CLL trial and is a potential new treatment option in this patient population. Turning to Slide 12, Breyanzi demonstrated a safety profile consistent with prior studies, with no new signals observed. Rates of Grade 3/4 CRS and neurological events were low and manageable.
Now, before we move on, TRANSCEND CLL is the first and only pivotal study where a CAR T-cell therapy has shown a significant improvement in this patient population, with no approved options after failing a BTKI and venetoclax. Additionally, we are excited about expanding Breyanzi even further into new potential indications as we announce the positive top-line data in relapsed or refractory follicular lymphoma and mantle cell lymphoma earlier this year. We will present both data sets later this month as late-breaking oral presentations at ICML. Starting on Abecma on Slide 13. Here you see the real-world efficacy and safety data published by the Myeloma CAR T Consortium earlier this year. In the real-world setting, the study showed that despite 75% of commercially treated patients not meeting eligibility criteria for the pivotal KarMMa study, they still observed comparable efficacy and safety results.
There were similar overall response rates and complete response rates, and Grade 3/4 CRS and neurotoxicity events were all in the low to mid-single digits. Furthermore, Abecma demonstrated strong manufacturing reliability in this commercial setting with a 94% success rate. These data support the confidence prescribers have in the reliability of Abecma's profile in patients treated in the commercial setting, and we continue to see important real-world evidence in BCMA-targeted cell therapies at ASCO this year. Turning to Slide 14, our GPRC5D targeting CAR T is a potential first-in-class agent in relapsed or refractory multiple myeloma. While BCMA-targeting therapies have transformed the treatment landscape in multiple myeloma, there is a need for new agents with novel mechanisms in the post-BCMA setting as more patients become relapsed or refractory to BCMA-targeting agents.
GPRC5D is an attractive target as it is highly expressed selectively on multiple myeloma cells, but not expressed on most other tissues. Slide 15 shows our phase I study design, which is a dose-finding study evaluating five dose levels, followed by a dose expansion cohort. The study enrolled patients who were post-transplant and triple class-exposed to an IMiD, proteasome inhibitor, and anti-CD38 targeting agent, and allowed patients who received a prior BCMA-targeted therapy onto the study. The dose expansion cohort is currently ongoing, and we anticipate initiating registration trials in early 2024. Moving to Slide 16. As a reminder of what we presented at ASH, we see encouraging depth and duration of response in heavily pre-treated, relapsed, and refractory multiple myeloma patient population. The efficacy and durability in patients who were both naive and exposed to prior BCMA-directed therapy look promising.
Particularly in the subgroup of patients who have received a prior BCMA-targeting agent, the overall response rate is 78%, with a complete response rate of 44%. Our GPRC5D CAR T was also well-tolerated, with low rates of Grade 3/4 CRS and infrequent neurotoxicity. We saw encouraging tolerability with respect to on-target, off-tumor adverse events affecting the skin, swallowing, or taste, potentially because targeting GPRC5D with a well-designed CAR T relieves the continuous target pressure seen with other modalities, such as the bispecifics. We look forward to presenting updated data at EHA on June 10th. Now, turning our attention to Slide 17, we see a new opportunity for Opdivo with the results of the SWOG S1826 cooperative group study. This is a phase III trial of Opdivo versus brentuximab vedotin, each on top of AVD chemotherapy in first-line advanced stage classical Hodgkin's lymphoma.
While classical Hodgkin's lymphoma is a highly curable disease, there remains a need for improved first-line options, as 7%-20% of patients with advanced stage disease still fail treatment. The trial enrolled both adult and pediatric patients, 12 years old and up, with newly diagnosed stage 3 or 4 classical Hodgkin's lymphoma. Progression-free survival is the primary endpoint, with overall survival as a key secondary endpoint. Patients were randomized one to one. It is important to note that prophylactic G-CSF was required in the brentuximab vedotin arm per the product label, but G-CSF was optional in the Opdivo arm. Looking at the results of the SWOG study on Slide 18, the Opdivo plus chemo arm showed superior PFS at 12 months and a hazard ratio of 0.48.
Opdivo is currently approved in classical Hodgkin's lymphoma for adult patients who have relapsed or progressed post-transplant. We believe the use of Opdivo chemo in first-line advanced classical Hodgkin's lymphoma provides a potential new treatment option for pediatric and adult patients. This study is still ongoing and will collect longer follow-up data. We are very encouraged by the data presented here at ASCO. We are working closely with SWOG on next steps as we analyze the full data set and prepare for future discussions with the regulators. On Slide 19, the safety profile of the Opdivo plus AVD arm was manageable and differentiated from the brentuximab arm in rates of neuropathies. We see lower rates of peripheral neuropathy in the Opdivo arm, 29% versus 55%, which may improve tolerability and adherence in patients.
Next, on Slide 20, I want to switch gears and talk to you about the lung cancer data we shared at ASCO, starting with the three-year follow-up results from the CheckMate -816 study for Opdivo plus chemo in neoadjuvant setting in the non-small cell lung cancer indication. The proportion of patients who had definitive surgery was numerically higher in the Opdivo plus chemo arm versus the chemo alone arm. Neoadjuvant Opdivo continues to demonstrate sustained clinical benefit in the metastatic lung setting. We are also pleased with what we saw in the CheckMate -9LA four-year follow-up data, particularly in the non- PD-L1 expressive population, where a significant unmet need still exists. The hallmark of IO is prolonged survival, which we see in the flattening of the curve. These data show long-term survival benefits in first-line lung cancer, with 21% of patients alive at four years.
Lastly, repotrectinib is our next generation potential best-in-class TKI targeting ROS1-positive non-small cell lung cancer. Repotrectinib continues to demonstrate high response rates and durable responses to patients with or without CNS metastasis. We are pleased with the continued progress we have made in lung cancer. Before I hand over to Adam, I'm sure you can see why we are very encouraged by our progress. We have a new potential option with Reblozyl in the first-line transfusion-dependent, lower-risk MDS-associated anemia. We're expanding our leadership in cell therapy with Breyanzi and Abecma, and we continue to improve outcomes for patients with lung cancer. I will now hand it over to Adam to share his thoughts from the commercial perspective. Thank you. Adam?
Thank you, Samit. Good morning, everyone. It's been a very good ASCO for Bristol Myers Squibb so far, as you just heard from Samit, we continue to make progress and generate compelling data advancing our hematology, cell therapy, and oncology franchises. If we could turn to Slide 22. We continue to demonstrate a strong presence at both ASCO and EHA, with significant disclosures across a broad range of diseases. Today, I'm excited to cover some of our commercial opportunities that are essential to both the current and future growth of Bristol Myers Squibb. Starting on Slide 23 and our opportunity with Reblozyl. Reblozyl has the potential to be the first approved treatment and a new standard of care in first line, lower risk MDS-associated anemia. What we hear from our customers is that the current treatment options with ESAs have significant limitations.
Few patients achieve transfusion independence, and when they do, they don't achieve a durable response. We know this is important because transfusion dependence increases mortality rates. Therefore, more effective and durable treatment options are needed. Reblozyl has a strong profile demonstrating superiority over ESAs in the COMMANDS trial, with twice as many patients achieving a response and showing a durability improvement of one year over ESAs, the durable benefit that was observed across RS subgroups. Additionally, we heard from Samit, and we hear from physicians that an every three-week dosing schedule is more convenient over weekly ESA treatment. Let's turn to Slide 24 to highlight our go-to-market strategy. COMMANDS had the opportunity to more than double the market and drive adoption for first line use of Reblozyl in MDS, based on its clinical profile and superiority over ESAs.
We plan to position Reblozyl as a new standard of care, displacing ESAs, as physicians want to provide the most effective and durable therapy available to their patients in front line. We have demonstrated strong performance in the second line setting, and I think the COMMANDS data just strengthen our confidence and continue to de-risk Reblozyl to achieve our goal of an excess of $4 billion of potential revenue in 2030. Our teams are launch-ready in the United States with a priority review PDUFA date of August 28th. Turning your attention to cell therapy on Slide 25. We continue to focus on growth and building our long-term leadership position in cell therapy. Bristol Myers Squibb is the only company with two approved and commercialized CAR T therapies addressing two distinct targets.
Breyanzi, which targets CD19, and Abecma, the first approved cell therapy to target BCMA, have made significant impact on improving patients' lives and has demonstrated strong demand in the market. Physicians clearly recognize Breyanzi's best-in-class strong clinical profile as further strengthened by its safety profile as a truly differentiated asset. Now, Breyanzi continues to generate strong demand with the broadest label in second-line plus large B-cell lymphoma. We now have the potential to expand the patient population beyond our large B-cell lymphoma indication in areas of high unmet need, including CLL, as well as follicular lymphoma and mantle cell lymphoma, where patients need more options. Abecma also continues to generate strong demand in relapsed refractory multiple myeloma as we continue to increase our supply.
First, let me just remind you, we recently published results from our KarMMa-3 study, highlighting deep and durable responses in difficult-to-treat triple-class exposed patients in the New England Journal of Medicine. These data are now under regulatory review across the United States, Europe, and Japan. What we think is really important is that our customers value the reliability of Abecma's profile. What do I mean by reliability? First, Abecma's strong clinical profile has been strengthened by the real-world experience, as noted by Samit earlier. Second, Abecma has a reliable safety profile, which is now clearly understood by physicians. Third, we continue to see strong manufacturing reliability with an outstanding manufacturing success rate of greater than 90%.
We continue to make a number of investments to increase our capacity for both of our cell therapy products, including vector sourcing as well as drug product, with our future new facilities in Devens, Massachusetts, as well as in Leiden, Netherlands, which will expand our footprint internationally. We're very pleased with the progress we're making on enhancing our manufacturing capabilities to bring these transformational innovations to more and more patients. We remain confident that both products will yield significant commercial opportunity over time. Our cell therapy platform continues to extend its potential beyond the success of Abecma and Breyanzi, as we look to providing more updates on our GPRC5D CAR T in multiple myeloma next week or later this week. We are well positioned with our current commercialized product and pipeline to lead in cell therapy into the future.
Now let's turn to Slide 26, where I'll discuss the important CHL data that was presented. What you heard during the presentation on Sunday, that these data are practice-changing. We've heard from our physicians, it's been very, very consistent. Opdivo plus AVD could be a paradigm shift for patients with first-line advanced CHL based on the data generated by the SWOG Cooperative Group. Recall, Opdivo is currently approved under accelerated approval in the United States in adults, in post-transplant relapse refractory in that setting. This is the confirmatory study that was agreed upon with the FDA. There remains a high unmet need in the frontline setting, where patients and HCPs continue to look for more effective and tolerable treatment options.
This year, there are estimated to be about 8,500 new cases of CHL in the U.S. alone, and the strong data, which demonstrated 12-month PFS superiority over brentuximab vedotin, gives great promise in this disease that, despite being highly curable, still has a need for more effective and tolerable options for patients. We continue to collaborate with SWOG on next steps and prepare for discussions in the future with regulators. We also look forward to sharing this data with NCCN, as we believe these results are clinically meaningful and could potentially be a new standard of care in treating CHL. Finally, as we turn to Slide 27, where we continue to provide options for patients for lung cancer, we have consistently said that the benefit of Opdivo and Yervoy comes with the hallmark of a flattening of the overall survival curve.
We see this clearly in the four-year overall survival data for CheckMate -9LA. This gives us an important opportunity to grow our first-line non-small cell lung cancer business, especially in the PD-L1 negative patients, as there still remains a significant unmet need in that patient population. In early-stage lung cancer, we've already established Opdivo as the standard of care in neoadjuvant disease with CheckMate -816 data, which positions us very well for the future. We look forward to potentially expanding into the peri-adjuvant setting with our CheckMate -77T data that's expected next year. These data will be very important to help physicians understand the optimal role of immunotherapy in the early lung cancer treatment setting and which patients actually need to go on to additional treatment in the adjuvant setting.
Finally, as Samit mentioned, repotrectinib was added to our portfolio from the Turning Point acquisition last year. We believe we have the opportunity to double the ROS1 market, and we're so excited about our opportunity to achieve best-in-class share based on the durable responses seen in patients with the ROS1 mutation. We're pleased with the recently announced priority review, the due date of November 27th, as the teams are currently preparing for launch in the U.S. Finally, on Slide 28, if I take a step back and tie it together. At BMS, we continue to make meaningful advancements in our leadership in oncology, hematology, and cell therapy with a broad set of programs across cancers. Importantly, the data presented here not only advance the science across our franchises, but also support our near-term and long-term commercial opportunities.
We continue to deliver strong execution and largely de-risk our new product portfolio. We see significant expansion opportunities for Reblozyl, moving to first line with the COMMANDS data, advancing our differentiated cell therapy business with Abecma, Breyanzi, and more data to come with our novel GPRC5D, as well as expanding opportunities across our important lung cancer business. I am excited for the future of Bristol Myers Squibb with our young and diverse portfolio and continued opportunities to solidify our leadership across hematology, cell therapy, and oncology. Now I'll turn the discussion back over to Tim. Tim?
Great. Thanks very much, Adam, and we're going to start getting ready for Q&A now. Just give us a minute to get the lines connected, and once we do, if you could put your hand up if you're in the Q&A room, so we know to go on, that would be great.
We are now ready for Q&A.
Terrific. Thank you. Can we go to our first question from Chris Schott at JP Morgan, please?
Just a reminder, if you'd like to ask a question, please select the Raise Hand feature at the bottom of your Zoom screen to enter the queue. Once Q&A begins, Tim Power will call out your full name and firm when it is your turn. When your name is called, you'll be prompted to unmute yourself, and once unmuted, you may ask your question. We will allow one question per person. No follow-up questions will be permitted.
Great, thanks again. Can we go to our first question from Chris Schott at JP Morgan, please?
Hey, can you guys hear me now? Sorry.
We can hear you now.
Okay, perfect. Thanks for the questions. Just from our perspective, maybe sort of a two-parter on the CAR T portfolio. Maybe just first on Abecma, in light of what we saw from CARTITUDE-4, can you just talk about how you're thinking about the competitive landscape on the BCMA side of things? Maybe the second part of this with the GPRC5D CAR T, how quickly can you move this forward? I think I heard 2024 registrational studies, I just wanted to confirm that. Maybe just more holistically talk about how you see that asset fitting in the treatment paradigm as we think about, I guess, bispecifics versus a CAR T approach for that target. Thank you.
Sure. Samit, do you want me to start with that one?
Yes. Maybe Rosanna, you can start with the GPRC5D, and then, of course, Lynelle, for the Abecma versus the CARTITUDE data would be good to follow.
Sure. Absolutely. I will say that, you know, really proud of our multiple myeloma portfolio, having multiple targets and multiple modalities of therapy. We are seeing a really rapidly evolving treatment landscape in multiple myeloma, as always, and we've seen intriguing data sets here at ASCO. Relating to the question on GPRC5D, we're extremely excited to progress this program forward. Related to the bispecifics, we've seen really interesting data here at ASCO of different bispecific therapies targeting both BCMA and GPRC5D, and the combination of both. And with this increase in modalities and targets that are available for the treatment of relapsed refractory multiple myeloma, I think it's important to think about the optimal way to sequence these different assets.
We've seen some data here and a nice discussion at the myeloma education session about the optimal way to sequence therapies. What we see is that we know with BCMA therapies from our own data in KarMMa, that antigen loss is rare, and so you can sequence BCMA, post-BCMA. With the data that we have on hand, we do believe that having and employing a CAR T therapy prior to a bispecific is the way to go. We've seen that with real world evidence. We've seen that with CARTITUDE-2, we've seen activity with T-cell engagers in that post-BCMA setting. That said, there is, there can be antigen, lower expression and immunogenicity that can take, that we need to take into account when we are sequencing in the post-BCMA setting.
This is where having a different target is really attractive. We are excited with the GPRC5D CAR T that we have. We think it's differentiated from bispecific in terms of the safety profile, and that may be due in part to the cellular genetics of giving a cell therapy, where you have that initial rapid expansion and then a nice downregulation, versus giving the continuous target pressure with a bispecific. We are seeing more on target, off tumor effects with the bispecific.
The combination data that we've seen with tec and tal is also validates, using both BCMA and GPRC5D, and we have as our BCMA, as our GPRC5D program progresses, we are thinking about combination therapies, and then we also have our bispecific CAR T, that's in the pipeline that we are excited to progress into clinical trials.
From there, I'll take the competitiveness. Actually, we've always felt that Abecma to be a very competitive asset, and actually the data that we have seen here at ASCO actually even brings greater confidence in our competitiveness. For one, the real world data that Adam had spoken about, we're seeing consistent and reliable results across efficacy, safety, and manufacturing. What does that mean for customers? What it means for them is what they can expect from a Abecma is something that no matter what patient they're putting on, they really can rely on with efficacy and safety, and more importantly, that they can get the product successfully from a successful manufacturing process. Further, what I would say, as we have seen additional data here at ASCO, it really also makes us confident in KarMMa-3. Remember, this is a patient population with a very high unmet need.
We had 95% of our patients that were Dara refractory, this is a highly convenient, I'm sorry, consistent with what the patients we see today and the treatment paradigm that we see today. When you think about that patient population and the efficacy we saw in KarMMa-3, we're quite confident. In addition, I think most of you know about the statistical methodology that is required by the FDA when assessing CAR Ts, and we're quite confident that our data also looks very strong from that prism as well.
Great. Thanks very much, Lynelle. Could we go to our next question, please, from Carter Gould at Barclays?
Great. I hope you can hear me. Good morning, everyone. Wanted to come back to the commentary on luspatercept. Samit, I appreciate your comments and highlighting sort of the longer duration of treatment. I think, you know, there's been some critique that, you know, the hazard ratio, you know, definitely, while impressive, the confidence intervals are fairly broad, and the denominators get rather small towards the tail end. Could you maybe just address your, you know, your confidence in the face of that commentary and maybe also comment how ELEMENTS fits into the strategy and if that maybe addresses any of the shortcomings of COMMANDS? Thank you.
Sure. Thank you. Carter, I'll start off, and certainly, Adam will add on a commercial perspective. The number one, this is a study, an intent to treat population, where all comer population was enrolled in the first-line setting and compared directly against an active treatment arm, which is ESAs. When we think about when the trial read out, it is still at the interim analysis that the trial read out from an efficacy perspective, we crossed the boundary, and therefore we were unblinded, and you've seen the results. We've also seen the results from a subgroup analysis perspective, which trend in the right direction for all of the subgroups.
You've also seen the forest plot, which shows very clearly that no matter how you look at it, from hypo levels, from mutation status, as well as from durability perspective as well, you see the equal efficacy across all the subgroups. The beauty of doing phase III trials in a randomized fashion, especially when you're comparing your drug against an active competitor, these are exactly the results that you want to see. If you think about what was presented at ASCO and what the investigators that did the study and the presenters said, as well as the discussants, they all said that these are truly the data that they were looking for as they think about applying them to their clinical practice.
Of course, when we submitted the data to the FDA, we've got our priority review as well. We're looking forward to that and bringing it to patients as soon as possible. From the ELEMENTS perspective, again, we are taking a step further now to apply these learnings and bringing it to the non-transfusion dependent population, so that patients can stay off of that transfusion, which creeps in in patients with MDS because the bone marrow does get impacted. We want to get these red cells to continue to mature so that the anemia doesn't creep in, and the patients don't have to go on to transfusion. As I said during the presentation, patients who become transfusion dependent have increased mortality, and the overall survival rate over five years, it continues to decline.
The longer we can stave off that transfusion dependence, the better it would be, and that's why ELEMENTS becomes important in the conduct. Adam?
Yeah, just coming back to COMMANDS, as we said, remember, COMMANDS was studied in an all-comers patient population, and it really was the first time in over 30 years where therapy showed superiority versus ESAs in lower-risk MDS. You know, as we've shared these data now with hematologists post the presentation, what they're telling us is that it's the durability of the transfusion durability and transfusion dependence have been really key regardless of RS status. You know, we do believe that Reblozyl will become a new standard of care in the first-line setting, regardless of RS status. As I mentioned, this significantly provides the opportunity to grow the addressable patient population. Our teams are launch-ready for our production date, and they're ready for a RS-agnostic label.
Thanks, Adam. Could we take our next question from Matt Phipps at William Blair, please?
Thanks, Tim. Hopefully you can hear me. Yeah, Adam, I mean, maybe just following up, can you contextualize a little bit of maybe how you see the market opportunity or how the market opportunity compares between RS-positive and RS-negative patients?
Yes, thanks. We were cutting out a little bit, RS-positive represents around, you know, 25%-30% of the, you know, of the patient population. as I talked about, when you look at the totality of the first-line business, you know, we believe that this opportunity will more than double the addressable patient population that we see in second line, which is the MDS patient population. We've been out there since 2020, with the second-line plus indication, where we've established Reblozyl as the standard of care in second line with our shares across the, you know, most of the markets are north of 70% in that second line RS-positive settings.
We feel really good about our opportunity to really move into the first line setting, which is a much greater opportunity for patients to achieve transfusion dependence and durability of response with Reblozyl.
Thanks, Adam. Thanks, Matt, for the question. Can we take our next question from Dane Leone, from Raymond James, please?
Hi. Oh, there we go. Yeah, so sorry to keep on this topic, but I think what we're all getting at here is there was a trend favoring ESAs on the primary endpoint for the RS-negative patient population. I think we're just trying to understand, you know, one, why the enrollment of the study actually skewed towards RS-positive, given the patient population should skew towards RS-negative. Does that actually infer clinical bias to the RS-positive patient, or is this incorrect, and your team does think we should be modeling adoption in the RS-negative patient population based upon the COMMANDS data? Thank you.
Thank you for the question. The way we have thought about it is, number one, there are two ways of looking at the overall data. One is the overall response rate, and the second is the longevity of transfusion independence. I think the mistake that many people make is to look at just the response rate part of it. It is, I think, more important because what we said earlier, transfusion dependence equals mortality in terms of the overall outcome for patients. If we can continue to stave off that transfusion for the longer duration, it is better for the patients. The trial was an intent to treat trial, meaning all comer patient population was the primary analysis, and we have shown statistic significance as well as clinically meaningful outcome overall from all patients' perspective.
In a similar way, as I said earlier, across the subgroups, you've seen all of that. From a trial enrollment perspective, certainly, geographical differences do occur. It's a heterogeneous population, and it is not just about RS positive and RS negativity in the clinical trial. There are number of inclusion and exclusion criteria that patients have to fit to be able to get enrolled in the clinical trial. All of that has to be taken into account, and that's why it is important to look at the forest plot as well as the stratified analysis that we conduct. Therefore, the application of the results applies to the overall population and not only in a subset.
The way we look at it is, how the study was conducted. That's why we've submitted the overall datasets to the FDA. We'll continue, of course, to follow up. We'll do an updated analysis at a later date and present the data in the future. This was an interim analysis-based outcome, where the study already met the outcome and the endpoints that were predefined. You'll continue to see the data. Of course, more excitedly, we are looking forward to the approval date on August 28th.
I'll just add, again, remember, this is an all-comer ITT patient population. You look at the, not just the durability of response, but also the safety, which is superior to ESAs. We believe that the $4 billion projection is not impacted at all. That's what we're continuing to model because, you know, we believe that this will be in a RS-agnostic label in the United States.
Great. Thanks, Adam. Can we take the next question from Terence Flynn with Morgan Stanley, please?
Hi, thanks so much for taking the questions. Maybe, just two quick ones for me. Samit, just wondering if you can confirm you don't anticipate an AdCom for luspatercept ahead of the PDUFA date here. On Opdivo in Hodgkin's lymphoma, congrats on the data there. I know you talked about a potential compendia listing. Can you just confirm how long that might take to get that on board here, what the timelines would be for compendia and first-line Hodgkin's? Thank you.
On the first one, I'll take that one, then, of course, I'll ask Adam to comment on the compendia listing part of it. For AdCom, for luspa, look, as we've said already, that we anticipate the outcome to be declared as per the PDUFA date in August. At this time, we do not anticipate, but these are regulatory discussions, and we don't comment specifically on what the outcomes could be. We'll certainly be communicating as we look to the approval in August of this year.
As it relates to the first line CHL data, as I mentioned, first, we're hearing from physicians that this is truly practice-changing data showing superiority versus Adcetris in a first-line setting. Samit and I both mentioned this is a SWOG study, and so, you know, not only we've been discussing these data with regulatory authorities, but, you know, working with SWOG, we will be submitting these data to NCCN for guideline adoption. As you're probably aware, each NCCN panel, you know, has their own criteria and takes different time to, you know, to make an assessment around, you know, placement on guidelines. We believe that guideline adoption will happen for first-line Opdivo in the coming, you know, weeks to months.
Maybe, Adam, if I can add a little bit more of the clinical context around this data, because, you know, at Sunday's plenary, we were really excited to see the data for a lot of reasons. First of all, this was an intergroup study that really harmonized adult and pediatric cooperative groups. That's important, right? Because this is a classical Hodgkin's lymphoma, which is predominantly a disease of adolescents and young adults. Why that's important is that the goals of therapy are not only to improve efficacy but to limit toxicities. We've seen really compelling efficacy with the hazard ratio of 0.48 that crossed the superior boundary with p-value of 0.0005. That was accompanied by a safety profile that's better than what the standard of care is.
You have a limit in the G-CSF that's used. That can cause bone pain. That really affects quality of life. Also that decrease in peripheral neuropathies, because you don't have the overlapping toxicities of brentuximab vedotin within blasting. That is important in terms of being able to continue therapy. That was shown in the study. I think, you know, we'll see longer-term data to see if there's any, you know, effects on delayed effects. The PFS advantage is important for an adolescent and young adult population because what that means is that less patients will need salvage therapy, which includes radiation therapy, high-dose chemotherapy, and transplant. We've heard from physicians on both the adult and pediatric side that this is really practice-changing data.
Perfect. Thanks, Rosanna. Just a quick reminder, if you want to ask a question, just put your hand up in the in the Q&A room. Could we take our next question, please, from Steve Scala on TD Cowen?
Hi, can you hear me?
We can.
Thank you. The question is, to what extent do you view Merck's KEYNOTE-671 peri-adjuvant regimen as a risk to Opdivo in the neoadjuvant setting? The Merck data is stronger, but not by much, and demands a higher treatment burden. I guess it could be concluded that the value of peri-adjuvant therapy is debatable. I'm wondering if you agree, are there any key differences in your peri-adjuvant trial versus KEYNOTE-671? Thank you.
I'll take the first part of the question, then turn over to Samit. Steve, thank you for the question. As I mentioned, I mean, CheckMate -816 is the standard of care in the market today. We have over 70% share, physicians continue to tell us that the Opdivo plus Yervoy really limited dose chemo is a significant advantage. You're right, when you look at the data that represented over the weekend, the data looks very similar.
PCR rates are almost identical. I do think that the CheckMate -77T data that we will read out sometime early next year will answer a lot of questions to understand, you know, which patients would require this, you know, for example, Opdivo chemo up front and would not need to go on to additional adjuvant therapy, and which of the patients might need additional therapy in the adjuvant setting. We look forward to receiving that data next year.
Yeah, I think you've covered it all, Adam. There's no, Steve, the trials are very similar, not much to add on top of what Adam's already said.
Thanks very much. I believe, Adam Jolly from Tim Anderson's team at Wolfe is on, could we go to Adam for Tim, please?
Hi, thanks. This is Adam on for Tim. Thanks for taking our question. Looking at ClinicalTrials.gov, it appears that the primary endpoint for part two of your phase II, [audio distortion] trial in lung changed from PFS to ORR last August. Can you clarify why this was changed? Thanks.
Well, when we are conducting a phase II study, we look at a multitude of endpoints. PFS is part of the inclusion in terms of the endpoints that will be assessed. It's only that ORR data will be available faster than the PFS data. From a decision-making point of view, we'll utilize that. It doesn't mean that we don't look at PFS. In fact, we will be looking at PFS as well and make decisions in looking at the overall data set from the part one of the study, which was this dose finding, and then the part two, which is the randomized portion of the study, where we will be looking at all parameters, not just ORR, not just PFS, but also biomarker analyses and others.
It's the totality of that data from within the clinical trial that will constitute our decision-making parameters.
Thanks so much. I believe Hao Shen from Geoff Meacham's team at Bank of America is on. Can we go to Hao, please?
Good morning.
We can hear you now. I can hear you now.
Okay. Okay, thank you. This is Hao on for Geoff Meacham, thank you for the question. Back to the SWOG and congrats on the data. Could you talk about the path forward for regulatory approval? Is that one-year PFS data sufficient, or you will have to wait for longer term?
Sure. Thank you. As Adam and Rosanna both mentioned, this is an intergroup study. When a study is a cooperative group study, while as Adam had also mentioned during his presentation, that this is a study that was agreed upon as a next step in terms of conversion of accelerated approval to full approval. It is important to understand that this is an intergroup study. We'll have to get the data from the SWOG group, analyze that data, and then obviously engage the regulators in terms of our conversations with them. We'll continue to keep you updated as we move forward in those. At the current time, we're looking forward to actually getting the data and analyzing that in a more complete way.
Excellent. I believe that, Harry Gillis from Luisa's team, with Berenberg. Can we go to Harry, please?
Hi there. Thanks for taking the question. I hope you can hear me. I was just wondering how confident you are that CheckMate -77T will actually determine which patients should continue with adjuvant therapy after neoadjuvant, and then perhaps which factors are likely to be important in this decision. Thanks for taking the question.
If you look at the overall data sets that are being generated, I don't think any one study will answer such a question. It's to be analyzing the data set across clinical trials because of the clinical characteristics that you really want to understand, as well as other markers of efficacy that one would isolate. If you think about neoadjuvant study, now there are a multitude of studies that have read out, showcasing that new adjuvant study is very important and already starts to impact the event-free survival. Of course, longer-term follow-up that we'll continue to have. Will there be a change or impact on the overall survival? We are now also getting the data from the adjuvant trials as well as periadjuvant trials.
It ultimately will lead to a meta-analysis of some sort, where we will be able to work with the investigators and other clinical trial statisticians, to be able to conform all the data sets together and then come to and draw conclusions. It's not just about 77T, but rather a amalgamation of the clinical trial data from various studies that will start to define the characteristics that may lead to that decision-making by investigators.
Thanks, Samit. Could we go next to Olivia Brayer from Cantor Fitzgerald, please?
Hey, good morning, guys. Hopefully, you can hear me, and thank you for the question. Can you share any FDA feedback on the ROS1 submission and maybe just your level of confidence coming out of those meetings? Is it fair to say that they've been supportive of a single-arm study now that you do have priority review, or is that still a potential risk here?
We of course, we comment on the specifics of the conversations we have with the FDA. As you've seen, we've submitted those single-arm trial data to the FDA. You already know that there is breakthrough therapy designation that has been granted to repotrectinib. You know, the submission that has been accepted, and we have a priority review. That is a conclusion to be drawn from those things, how FDA is looking at this data. Beyond that, we will not be able to comment on the specifics of the conversations we have, as we never have. Thank you.
Great. Can we take our next one from, I think Mohit Bansal's team are on. I think Cerena might be representing Mohit, from Wells Fargo.
Hi, thanks for taking our question. Since Geron's and imetelstat also showed positive data in lower risk MDS, can you guys talk about the relative profiles of Reblozyl versus imetelstat in this setting? Thank you.
Yeah. There are obviously more and more data that are emerging in of the lower-risk MDS. Remember, luspatercept was the first one to show as a new class of agent that showed an impact on transfusion independence in the second-line setting first, and now we have the data in the first-line setting. We also obviously have an approval in beta thalassemia as well for the transfusion-independent, the transfusion-dependent population, and in Europe, also in the transfusion-independent population. Overall data set that are available for luspatercept remains much larger than anybody else. Second thing to note is how you look at patient populations enrolled in the various programs as well as the endpoints that are analyzed. Some have analyzed a shorter duration of transfusion independence.
If you think about eight-week transfusion independence versus the one that we've looked at, 12 and 24 weeks of transfusion independence, it's easier to achieve eight-week transfusion independence as opposed to 12 or 24 weeks. Those longevities are important. The second, we also looked at what was presented in terms of the EPO levels. We've obviously treated a much difficult to treat population who have less than 500 EPO, whereas others have treated more than 500, another differentiating feature. I think overall, we are very confident and very energized and excited about the data that we've continued to generate.
As I said earlier during the presentation, we still have multitude of other studies that are ongoing that will add on to the data sets for Luspatercept, whereas the safety profile remains very consistent across the clinical trials.
Yeah. So I think there are just a couple things I might add. You know, as we look at the data, number one, when you see the adverse event profile for luspatercept versus imetelstat, there's a extremely high rate of cytopenias in the Geron study that we know are, you know, rate limiting. There was a discontinuation rate of, you know, almost 80% in that study. So patients are unable to tolerate the product. Also, we know when we look at the administration route, remember, imetelstat is administered as a two-hour IV infusion. We look at the, you know, the sub Q, every three-week dose for Reblozyl is seen as being, you know, very, very convenient for patients.
You know, we believe that our COMMANDS and first line and first setting really are gonna be standard of care in that setting. We look at, you know, patients who might need a secondary treatment, that's potentially where they could use imetelstat.
Terrific. Thanks, Adam. We have Colin Bristow's team from UBS, can we go to them, please?
Hi, this is [Yihan Ang] for Colin. Congrats on the progresses, and thank you for taking our question. We have one question on the Opdualag. Should we still expect the phase II data read out in the first-line lung non-small cell lung cancer later this year, you previously guided, or it is actually more realistic to see the data early next year? Also, we are wondering what kind of data set should we expect to see. Thank you so much.
We obviously have the ongoing study in non-small cell lung cancer. The randomized setting, it's a phase II study. We anticipate to see the data either very late this year or most, more likely to be early next year. In terms of the what kind of data set, of course, when we present the data, it is going to be inclusive of multitude of things in terms of patient population roles that have clinical characteristics as well as from a safety and efficacy endpoints that we've included in the clinical trial and some levels of biomarkers.
If it's a study and if it's a data presentation, of course it will be more comprehensive, because we also have to make decisions in terms of where we go from once we have the data to when we have the data in our hands. Looking forward to that ourselves, and we'll keep you posted as the data comes.
Great. Thanks. I understand that we sort of, we've run out of questions at this point. I just wanna thank everybody for your participation today. If you've got follow-ups, you know where to find us in the IR team. Have a good day.
Thank you.