Bristol-Myers Squibb Co
NYSE:BMY
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Bristol-Myers Squibb Co
Earnings Call Analysis
Q3-2024 Analysis
Bristol-Myers Squibb Co
In the third quarter of 2024, Bristol-Myers Squibb (BMS) reported a strong performance, driven by solid demand across its growth and legacy product portfolios. The growth portfolio, which now contributes about half of the company’s total revenues, experienced a remarkable 20% increase in sales at constant currency. This growth momentum is expected to continue as the company emphasizes near-term execution while laying the groundwork for sustainable long-term growth.
The company has seen exceptional sales across key products. Notably, sales of Reblozyl skyrocketed by 81%, while Breyanzi’s sales more than doubled due to strong demand for new indications. Additionally, the recently launched medication Cobinfi is projected to become a significant growth driver, addressing a substantial unmet need in the schizophrenia market with approximately 1.6 million patients treated annually in the U.S.
BMS is keen on maintaining financial discipline, achieving strong operating cash flow of approximately $5.6 billion in the last quarter. The company is also on track to realize the majority of its $1.5 billion cost savings initiative this year, focusing on more efficient operational practices. Despite a 130 basis point decline in gross margin due to product mix, operational cost management is expected to support a stable operating margin target of at least 37% for the fiscal year.
Given the robust performance and innovative product pipeline, BMS is raising its revenue guidance for 2024. The full-year revenue is now expected to grow by approximately 5%, and around 6% when adjusted for constant currency. This uplift is largely driven by higher-than-expected sales of Revlimid, which has been updated to around $5.5 billion for the year. The company anticipates that other legacy brands might experience pressures due to anticipated generic competition.
BMS continues to enhance its product pipeline, with promising progress noted in oncology and immunology. The company plans to present Phase I data for CD19 NEX-T cell therapy and expects FDA approval for a subcutaneous formulation of nivolumab by year-end 2024, a launch projected for early 2025. Such advancements are crucial for ensuring sustained growth into the next decade.
Amidst the strong growth trajectory, BMS remains committed to enhancing shareholder value. The company is focused on reducing its debt, aiming to pay down around $10 billion by mid-2026 while continuing to pay dividends and strategically investing in growth opportunities. The balance sheet strength, alongside the operational efficiencies being implemented, provides a solid foundation for future performance.
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Good day, and welcome to the Bristol-Myers Squibb Third Quarter 2024 Earnings Conference Call. [Operator Instructions] Please note this event is being recorded.
I would now like to turn the conference over to Mr. Chuck Triano, Senior Vice President of Investor Relations. Please go ahead, sir.
Thank you, and good morning, everyone. I'm happy to be here at Bristol-Myers Squibb, and we appreciate you joining our third quarter 2024 earnings call.
Joining me this morning with prepared remarks are Chris Boerner, our Board Chair and Chief Executive Officer; and David Elkins, our Chief Financial Officer. Also participating in today's call are Adam Lenkowsky, our Chief Commercialization Officer; and Samit Hirawat, our Chief Medical Officer and Head of Global Drug Development.
Earlier this morning, we posted our quarterly slide presentation to bms.com that you can use to follow along with Chris and David's remarks.
Before we get started, I'll remind everybody that during this call, we will make statements about the company's future plans and prospects that constitute forward-looking statements. Actual results may differ materially from those indicated by those forward-looking statements as a result of various important factors, including those discussed in the company's SEC filings.
These forward-looking statements represent our estimates as of today and should not be relied upon as representing our estimates as of any future date, and we specifically disclaim any obligation to update forward-looking statements even if our estimates change.
We'll also focus our comments on our non-GAAP financial measures, which are adjusted to exclude certain specified items. Reconciliations of certain non-GAAP financial measures to the most comparable GAAP measures are available at bms.com.
And with that, I'll hand it over to Chris.
Thank you, Chuck, and thank you all for joining us this morning. Starting on Slide 4. Our third quarter results reflect our continued focus on near-term execution and building the foundation for long-term sustainable growth. During the quarter, we saw solid demand for key products across our growth and legacy portfolios.
We remained disciplined in managing expenses, and we continue to advance important pipeline programs. Let me highlight a few achievements in the quarter. Growth portfolio revenues increased 20% in Q3 at constant currency and now account for approximately half of total revenues. These are primarily young assets that have exclusivity well into the next decade.
Our legacy portfolio also performed well, generating cash flow that allows us to strategically invest in growth opportunities. During the quarter, we achieved several clinical and regulatory milestones. Notably, we reestablished our presence in neuroscience with the approval of Cobinfi, which I'll speak to in a moment. We also strengthened our leading oncology portfolio. And earlier this month, we received FDA approval for an OPDIVO-based perioperative treatment regimen in non-small cell lung cancer.
Additionally, we continue to advance our innovative pipeline. In oncology, we presented data at ESMO, highlighting 8 new registrational opportunities. We shared positive clinical data for our nivolumab plus rolatlimib high-dose combination in first-line lung cancer, which is now advancing to Phase III.
And we talked about the progress we're making across other promising assets and modalities, including our bispecific ADC and our radiopharmaceutical pipeline. This past week, at ENA, we also presented promising Phase I data for our PRMT5 program across all the tumors.
Turning to Slide 5. The acquisition of Karuna Therapeutics is a key example of how we are strengthening our long-term growth outlook. We're proud to highlight the recent FDA approval of Cobinfi, formerly known as KarXT with a strong label that reflects its efficacy and safety profile. This milestone marks significant progress in delivering value from the Karuna acquisition for patients. Cobinfi is the first truly novel mechanism approved for adults with schizophrenia in decades, and it addresses 1 of the most significant unmet needs in mental health. There are approximately 1.6 million people being for schizophrenia in the U.S. alone, many of whom have endured debilitating side effects from older treatments.
Cobinfi delivers compelling efficacy without the notable side effects associated with atypicals. The BMS team has been laying the groundwork for a successful launch. We built an experienced sales and medical team engaged with payers to secure access and develop sophisticated patient support services. We have ongoing clinical programs in adjunctive schizophrenia with Phase III data expected in 2025.
And we have expanded the ongoing ADEPT program in Alzheimer's disease psychosis with Phase III data expected in 2026. We remain on track to start registrational trials next year in Alzheimer's agitation, Alzheimer's cognition, bipolar disorder and autism spectrum disorder. Adam and Samit can speak more to our launch progress in schizophrenia and other potential indications, we are actively assessing for Cobinfi in Q&A.
Turning to Slide 6. I'll spend a moment updating you on our progress against our key strategic priorities. First, we're focused on transformational medicines where we have a competitive advantage. We are advancing our mission to serve patients with first or best-in-class treatments across our therapeutic areas. This includes driving leadership in hematology, cardiology and oncology therapeutic areas with products like Reblozyl, Breyanzi, KEMZyOS and OptulAg.
At the same time, we're strengthening our innovative pipeline by prioritizing key programs. 1 asset that continues to advance well as milvexian. We continue to see considerable unmet need across indications, in particular, AF as well as a large commercial opportunity. Today, we want to share an encouraging update related to our atrial fibrillation Phase III trial, which continues to recruit very well. As you'll soon see on clinicaltrials.gov we and our partner, J&J, have approved an increase in patient enrollment side.
This is because at this time, based on review of event rates, we are seeing a lower rate of strokes and systemic embolism than originally anticipated, and the increased enrollment supports maintaining the planned data readout in 2027. As a reminder, as described in our published study design paper, we indicated that the sample size may be adjusted based on review of event rates. We remain confident in the design and progress of the program. Beyond milvexian, we continue to advance other programs where we have a right to win. This includes our CD19 NEX-T cell therapy, our radiopharmaceutical and protein degradation platforms as well as additional indications for Cobenfi.
Our second priority is driving operational excellence. We are reviewing overall spending and prioritizing investments that will deliver the best long-term returns. We remain on track to deliver $1.5 billion in savings by the end of 2025. And -- these savings will be reinvested into high ROI opportunities that serve patients' needs and accelerate growth.
We are becoming a more agile company with stronger commercial and pipeline execution. Our progress on this front was demonstrated by the performance of our growth portfolio in Q3, the approval of Cobinfi and acceleration of key programs. We see the drive for greater operational excellence as a continuous process. As such, -- we're exploring opportunities to further improve productivity and efficiency over the coming quarters. Our third priority is to strategically allocate capital for long-term growth and returns.
We remain focused on our near-term goal of delevering our balance sheet. We made further progress during Q3 and are on track to pay down our target of $10 billion of debt by the first half of 2026. We're committed to the dividend, and we will continue to invest strategically in growth through our own pipeline as well as sourcing innovation externally. Now turning to upcoming milestones on Slide 7. At the American College of Rheumatology's Annual Meeting in November, we will present promising Phase I data for our CD19 NEX-T cell therapy. This is a next-generation immunology asset, leveraging the Breyanzi construct.
We are optimistic about its potential to deliver benefits for patients across multiple immunology indications by resetting the immune system. In late December, we expect the FDA's decision on the subcutaneous formulation of nivolumab. We anticipate this launch in early 2025 will provide an important benefit for both patients and physicians while extending our leadership in immuno-oncology into the next decade.
We're also on track to share top line Phase III data from SOTYK2 in psoriatic arthritis by year-end. This data should help strengthen the competitive profile for SOTYK2 as roughly 1/3 of psoriasis patients also have psoriatic arthritis.
Turning to our outlook on Slide 8. Given the strength of our results year-to-date, we are raising both our full year revenue target and our full year EPS guidance. David will discuss these updates in more detail shortly. Looking ahead, I'm confident in our ability to deliver long-term value for patients and our shareholders.
To summarize on Slide 9, I'm pleased with our achievements in critical areas. Our overall business mix is beginning to transform as our growth portfolio is becoming a bigger component. The U.S. approval of Cobinfi adds another asset with multibillion-dollar potential to serve more patients and accelerate growth.
Our pipeline continues to advance with additional near-term catalysts and we are maintaining a disciplined focus on expense management, driving initiatives across the company to lower cost. These actions underscore our focus on executing in the near term while laying the groundwork for long-term sustainable growth. We look forward to keeping you updated as we build momentum with important milestones in 2025 and significant data flow in 2026.
Before I close, I want to thank our employees for their dedication and performance in the quarter. Together, we are building a strong future for BMS and the patients we serve. Now I'll turn it over to David.
Thank you, Chris, and good morning, everyone. I'm pleased to share our quarterly financial performance. As a reminder, unless otherwise stated, all comparisons are made from the same period in 2023 and sales growth rates will be discussed on an underlying basis which excludes the impact of foreign exchange, all references to our P&L on a non-GAAP basis.
Let's start on Slide 10 with some highlights from our third quarter sales. we demonstrated solid commercial performance in the third quarter with higher sales driven primarily by our growth brands. The growth portfolio delivered another quarter of double-digit growth, up 20% with continued progress across key brands, including Reblozyl, Breyanzi, and Our legacy portfolio also performed well with U.S. growth led by Eliquis, partially offset by lower sales of Sprycel. As a reminder, the LOE for Sprycel in the U.S. recently occurred on September 1, and the LOE for POMALYST in Europe happened back in August.
Our continued focus on commercial execution enabled us to deliver nearly half of our sales in the third quarter from the growth portfolio. And with the recent U.S. approval and launch of Cobenfi, our sales mix will continue to diversify and provide a stronger foundation for growth. Importantly, we will continue to optimize the strong cash flow generated from the legacy portfolio to invest in growth opportunities.
Before going into key brand performance, it's important to note that third quarter sales were impacted by the reversal of an approximate $150 million inventory build from the second quarter. This tempered growth across several brands, primarily Opdivo, and as well as Optulag, KEMZYOS and some immunology products.
Let's start with our oncology business on Slide 11. Global sales of Opdivo were higher in the third quarter, reflecting solid demand growth outside the U.S. Looking ahead, we continue to expect global full year sales growth to be in the mid-single-digit range. We remain focused on the anticipated approval and launch of the subcutaneous formulation of nivolumab which, as Chris mentioned, is expected to receive FDA approval by year-end.
With this anticipated approval, we will have the potential to extend the durability of our immuno-oncology portfolio into the next decade. Moving to Optolag, we delivered strong double-digit growth in the third quarter, driven primarily by demand. 3 years post launch, Optulag has become a standard of care in first-line melanoma in the U.S. with 30% market share.
Outside the U.S., third quarter sales benefited from the strong uptake in newly launched markets such as the U.K., Brazil and Australia. Moving to our cardiovascular portfolio on Slide 12. Eliquis is the leading anticoagulant worldwide and delivered double-digit sales growth in the third quarter. U.S. sales benefited from the higher demand and market share gains.
Sequentially, as we've seen historically, U.S. sales included an unfavorable gross to net impact related to the Medicare coverage gap. Outside the U.S., sequential sales of Eliquis reflected higher demand across key markets and favorable inventory compared to the prior quarter.
Turning to KEMZYAS. Third quarter sales more than doubled, driven by strong U.S. demand for new patient starts and an increasing number of patients on commercial drug. During the third quarter, we saw steady patient adoption with nearly 20% growth in patients on commercial drug, more than doubling the number from a year ago.
Outside the U.S., sequential sales growth reflected higher demand in newly launched markets in Europe. Now let's turn to hematology on Slide 13. Sales of Reblozyl grew 81% in the third quarter, with strong double-digit growth, both in the U.S. and international markets. The U.S. sales were driven by continued demand in first-line setting, outside the U.S., recent first-line reimbursement in Europe and Japan contributed to the strong performance in the quarter.
In cell therapy, sales of Breyanzi more than doubled versus prior year, driven by demand in new indications and improved manufacturing capacity and reliability. In the U.S., sales grew more 40% on a sequential basis driven primarily by pent-up demand in 2 of our newly approved indications, follicular lymphoma and mantle cell lymphoma. We expect more modest sequential growth from third quarter to fourth quarter as demand normalizes.
Also in cell therapy, despite a competitive market, bema performed well in the third quarter with solid demand growth in both the U.S. and international markets. Now moving to immunology on Slide 14. Sales SOTYKTU nearly doubled when compared to the impact of the $30 million clinical trial purchase in the third quarter of last year.
Outside the U.S., sales grew year-over-year, benefiting from the launch in a number of international markets. Looking to the fourth quarter, we expect a step-up in gross to net discounts resulting from increased rebating associated with our approved access position. This would result in the fourth quarter sales being similar to this quarter.
As we said previously, we expect that over time, demand growth will offset these pressures. Now turning to the P&L on Slide 15. In addition to solid commercial execution, our third quarter performance demonstrated our focus on financial discipline and steady progress against our $1.5 billion cost savings program.
As a reminder, we initiated this program to offset incremental OpEx from the recent deals. Savings from across the organization include reductions in direct clinical trial expense, site rationalization, elimination of roles and a reduction in headcount. As we said previously, we expect the majority of the savings to come through this year. As we realize these savings, we are strategically reinvesting in high potential opportunities to fuel long-term growth and innovation in key areas.
Moving to gross margin. We saw a decline in the quarter of about 130 basis points, driven primarily by product mix. Operating expenses, excluding in-process R&D were impacted by higher deal-related spend, partially offset by savings from our efficiency initiatives.
Our effective tax rate in the quarter changed from 11.6% in the prior year to 18.5%, impacted by onetime adjustment in 2023 resulting from newly issued IRS guidance. Overall, third quarter earnings per share were $1.80. Now moving to the balance sheet and capital allocation highlights. We ended the quarter with approximately $8.4 billion in cash, cash equivalents and marketable debt securities on hand.
During the third quarter, both our growth and legacy portfolios delivered solid revenue growth, contributing to robust operating cash flow of approximately $5.6 billion. In terms of capital allocation, we remain focused on strengthening our balance sheet. We are executing our plan to pay down approximately $10 billion of debt. And relative to our position at the end of the first quarter, we have reduced it by $5.9 billion. This includes roughly $3 billion of commercial paper and 2.9% of long-term debt.
As we previously have said, we remain committed to our dividend. Our strong cash flow profile enables us to address these priorities while also strengthening our outlook. Turning to 2024 non-GAAP guidance. As is our practice, we provide revenue guidance on a reported basis as well as on an underlying basis, which assumes currency remains consistent with prior year.
We now expect full year 2024 revenue to increase approximately 5% as reported and approximately 6% at constant currency, primarily due to higher-than-anticipated sales of REVLIMID. We are pleased with the performance of both growth and legacy portfolios. And in legacy, we have updated our full year sales estimate of REVLIMID to approximately $5.5 billion.
As a reminder, for modeling purposes, in addition to Revlimid, other legacy brands should soften in the fourth quarter due to competition from generics for ABRAXANE in the U.S. and PAMALISin Europe. Turning to gross margin. We now expect a slightly tighter range to reflect the impact of our U.S. sales mix. Excluding acquired impresses R&D, we now expect total operating expenses for the year to increase approximately 4% to 5%. This increase reflects higher fourth quarter spending to support our product portfolio and pipeline and is in line with fourth quarter increases seen in previous years.
These costs are partially offset by savings from our productivity initiatives. We remain confident in our ability to achieve our full year operating margin target of at least 37%. For OI&E, we have increased our estimate from approximately $50 million of expense to approximately $125 million of income due to better-than-expected royalty and interest income.
As a reminder, our tax rate was impacted by the nondeductible charge for acquired in process R&D, primarily from the Karuna acquisition in the first quarter. Excluding the acquired in-process R&D, we continue to expect estimated underlying non-GAAP tax rate for the full year to be approximately 18%. Taking these updates into effect, we are raising our non-GAAP EPS guidance to a range of $0.75 to $0.95.
In closing, our third quarter results were marked by significantly higher sales across key growth brands. robust cash flow generation and continued financial discipline. As we reestablish our presence in neuroscience with the U.S. launch of we are excited about the long-term opportunity of this brand and its potential to serve more patients. We're looking forward to additional near-term catalysts as our pipeline continues to advance.
Our solid performance year-to-date supports our raised full year guidance and our increased confidence in our ability to drive long-term sustainable growth.
And with that, I'll now turn the call back over to Chuck for Q&A.
[Operator Instructions] And your first question will come from Evan Seigerman with BMO Capital Markets.
Congrats on the progress this quarter. So 1 for Adam, now that you have approved. Can you walk us through what the next year looks like when it comes to access? I know there's a lot of puts and takes when it comes to Medicaid and commercial. But maybe give us some color as to how we should think about it?
Adam?
Yes. Thanks, Evan, for the question. We're very excited about the approval of Cobenfi. As you heard from Chris, is the first innovative therapy approved in schizophrenia in decades. And we're very pleased with the label does not carry the atypical antisycotic class warnings and precautions or a box warning.
And so how we think about this addresses a large market. Remember, there are 1.6 million people treated for schizophrenia each year in the U.S. We do see this as a 2025 launch with the launch picking up after attaining broad access. We expect to see sales ramp in the second half of the year, and I'll describe those dynamics.
First and foremost, we're really excited that product is available this week. Our field teams are out now selling. They're engaging with customers. And so we'll see stocking this year. Now access is a gating factor to sales uptake as over 80% of patients are either Medicare or Medicaid.
And just remember, schizophrenia is a fundamentally different market than markets that are highly PBM driven. So we expect to take about a year to achieve 80% to 85% access. It could move a bit faster in Medicaid and we're certainly going to work to accelerate that.
So the way to think about is really in a step-wise fashion. In Medicaid, recall roughly half of the states have 0 to 1 step access. And so deep Medicaid P&T meetings will take place over the course of the next several months. We've already seen a few states come online this week. Physicians can prescribe once P&T reviews are completed and we are working to expand access across the remaining states.
Now in Medicare, recall, this is a protected class. So payers have 90 days to make a coverage decision, and we expect to see mandatory coverage determinations in Q1, but in the meantime, physicians can push through medical exemptions before any of these formulary reviews take place. Our asset teams have been meeting with payers for some time, and our team without immediately post approval with payers to review the approved label and the response has been very, very positive.
So again, we know the work that we need to do to maximize this important launch, and we plan to make this a very big product for our company over time.
Next question will come from Chris Shibutani with Goldman Sachs. .
Certainly, you've been doing a lot to focus the operating expense profile here. And at the same time, you're seeing improving top line -- where are you in that trajectory in terms of what we should expect 2025? Any early commentary on the shape of 2025 top line dynamics as a function of operating expense would be helpful.
Thanks, Chris. I'll ask David to take that one.
Yes, Chris, thanks for the question. And look, we feel really good about the progress we're making on our $1.5 billion savings initiatives that we had in place. And you recall -- we're on track to achieve the majority of that this year.
We also feel really good about the operating margin guidance that we provided of at least 37% both this year and for next year as well. So we're continuing to look for efficiencies in our cost base, and you'll continue to hear more about that. But as it relates to '25, we're going to give you full line guidance like we typically do on our fourth quarter earnings call.
Your next question will come from Chris Schott with JPMorgan.
Just maybe a 2-parter on Just thank you for all the details on the reimbursement piece. Once reimbursement is in place, can you just talk about how you're thinking about the ramp of the drug from there?
I guess, historically, I think we've seen more gradual launches in schizophrenia, but these are largely assets with similar mechanisms to existing products. I'm just wondering in this case, are you anticipating this could be a faster ramp than we've historically seen given the unmet need and your unique mechanism of action?
And then just my second part on the same product is just when you think about the additional line extensions here, what's your confidence in the bipolar 1 opportunity? It's obviously a very large market and live data you've seen in schizophrenia, do you view that as a high probability of success study as you start to ramp that one?
Thanks, Chris. Adam will take the first part, and then Samit can chime in as well.
Yes, Chris, thanks for the question. First thing I'd say is there's really no perfect analog here because unlike previous launches, where you've seen multiple success of approvals, for example, schizophonia that MDD. That's not going to be the case with approval cadence is going to be in schizophrenia, first in monotherapy than adjunctive therapy.
As I said, in terms of the -- as we see the launch an access coming online, really, this is going to be a second half ramp. That's how we see it. So physicians can prescribe today push through medical exemptions before formulary reviews, but we expect to see really full access 80 to 85 access within roughly 12 months post approval.
Yes. And thanks for the question, Chris. If you think about bipolar, so if you think about mania in general, bipolar one, that includes symptoms that are excessive activity as well as the psychotic symptoms of delusion, hallucinations and thought disorders. Then Xanomeline and especially as we think about has demonstrated reduction of these agitation symptoms in Alzheimer's disease as well as in schizophrenia, Alzheimer's data, of course, came from the 1997 study that was published for in the past.
So these are all predictive of efficacy potential in bipolar mania. There is no evidence thus far in the studies that have been conducted in the emergent program that shows a worsening of the depressive symptoms. So taken together, we are looking forward to initiation of that program in bipolar mania in the middle of 2025.
Just to also add to on top of that beyond bipolar in 2025, we are looking forward to the readout of the ARISE trial, which is the schizophrenia trial. And of course, 2 additional indications that we will be initiating in 2025 will be AD agitation as well as recognition.
Next question will come from Luisa Hector with Berenberg.
On SOTYKTU, you mentioned the price impact in Q4, but could you add a little more color on the outlook for next year and the access and pricing as we roll into next year? And then perhaps just a reminder of the profile that you're looking for in the ceraticarthritis trial.
Adam can take the first 1 and then, Samit.
Thanks, Louisa. As we said in the past, the TC2 performance has been slower than we'd like, and we are making progress on executing against our plan. And that's securing favorable access and ultimately improving performance and execution. Recall, we had 25% access in the first half of the year. We more than doubled that in Q3.
We now have approximately 50% 0 step edits in the market. And I could say we are having productive conversations with the remaining payers and expect to enable broader access and adoption in 2021. But this comes with significant rebating and gross net impact that will be compensated by increased volume over time. It's going to take a few quarters for that to wash out.
In fact, in Q3, you saw some of this. We saw some of the pull-through delivered both versus prior year and sequentially when you exclude clinical trials. So this is a market that is going to remain highly competitive, and we're going to continue to work to increase more market share as well as paid prescriptions. But as we exit this year, we will be in a better position versus where we started the year, and we're going to work to be more competitive.
Thanks for the question, Louisa, for the arthritis part. Remember, we have been able to pull and accelerate the readout of the second study as well. So we are looking forward to the readout towards the end of this year for both poetic politic PSAI within 2024.
Overall, as you can imagine, since a lot of data has now been generated from a safety and efficacy perspective for SOTYKTU in psoriasis the readout of the program will put us in the right footing as we think about the competitor profile versus as well. So looking forward to that, we have no concerns from a safety perspective as we've said, so hopefully, the studies read out positive, that will lead to a filing in 2025.
The next question will come from Geoff Meacham with Citibank.
For Chris or Samit on the milvexian program, I know you guys did talk about the use of -- the potential to upsize the trial previously. But -- what would you say is the cause for the lower event rate? Does this change the risk profile? We know that GLP-1s have an impact, for example, in cardiometabolic trials, you think changes there commercially could have changed the event rate in your study?
Thanks, Geoff. I'll start, and then I'll turn it over to Samit. Let me just say at the outset, Geoff, that we're encouraged by what we're seeing with this program. Just a reminder, we're developing milvexian because there remains high unmet need for patients in anti-coagulation. That's particularly true in atrial fibrillation, where as I think you know, this is an area where 40 million individuals worldwide have atrial fibrillation.
And that despite the success of Factor Xa like Eliquis, about 40% of those patients remain on or undertreated due to the risk of bleeding. And we believe milvexian has the potential to improve the outcome for these patients. The update that we provided today is really intended to give some context to the decision to increase the sample size given the encouraging blended event rates that we're seeing at this point in the study.
This is a potentially important medicine. We want to do everything we can to ensure that the program continues to read out in 2027. But before I turn it over to Samit. I want to leave you with, we're encouraged by what we're seeing here, and we look forward to seeing this study come to its outcome in 2027. Samit?
Yes. Thanks, Chris. And Geoff, just extending from where Chris left off from an encouraging point of view, remember where we started the program from. What we have seen from trial in AF, it was very clear that one of the key drivers of the outcome was the dose. .
We started the milvexian program with well-designed Phase II studies that led us to pick the right doses for our Phase III programs in AF as well as in combination with agents in ACS as well as Secondly, our event rate is lower compared to what we had designed the study for at the current time. And that gives us the reason to increase the sample size, which you will see the numbers when we update centrals.gov.
Thirdly, as we think about why the study was started, the genic study was stopped because the DMC reviewed the data and saw almost more than -- almost 3x the event rate on the investigation arm in that study. Our study is periodically reviewed by the DMC. There are no indications from the DMC that we should go any other route and they are supportive of continuing the study at this time. We truly are encouraged by all of this. And as you know, ACS as well as the SSP programs are slated to read out in 2026, and we are on track for that.
Next question will come from Carter Gould with Barclays.
Maybe I don't mean to hammer on it again, but just wanted to follow up on the prior question for Samit there. With the increased patient enrollment, will there be any shift in the criteria or enrichment of patients away from the of our proximal segments. I mean, I appreciate your commentary on what happened to your competitor but at the same conversation at ESC, there was talk about the challenges in those populations given especially what seems to be going on here at the event rate. Any color would be appreciated.
Yes. Thank you, Carter. There are no plans to change any of these criteria. We will continue to observe them and the study will continue as is, except for the change in the sample size.
Next question will come from Mohit Bansal with Wells Fargo.
This is Serena on for Mohit. We wanted to dig more into the KarXT development plans as it relates to cognition. Perhaps starting with the AD psychosis trial, I was wondering if it will still have the 3x in 1 day dosing and longer titration period.
And then moving on to the cognition trial. Was wondering what this could look like, like would it need to be longer than the emergent studies? And do you plan to enrich for patients cognitively impaired at baseline.
Yes. Thank you, Serena, for the question. So we're looking forward to, obviously, the initiation of 3 Phase III programs next year, 1 in AD agitation, second in bipolar third in the recognition program. The reason for belief of course, is the dual mechanism of action in terms of M1 and M4 direct agonism that is obviously associated with xanomeline as well as the available data from the old studies that were conducted with xanomeline that already showed the right trend in terms of the cognition improvement in those studies. .
Your question around the 3x a day dosing right now that is built into the AD psychosis program. We are working on the BID dosing for these patients, and there will be instituted in the new study that we will start in the 3 indications that I talked about as well as we are thinking about how we will institute a bridging program so that we can bring it back into the AD Psychosis program as well.
Overall, in a good track and certainly looking forward now to the readout of the ARISE study next year.
Next question will come from Chun Chen with UBS.
Just 1 on the recent data. We saw an ORR of 21% across the a bunch of solid tumors. Can you perhaps talk about efficacy as regard to durability that you're seeing here with the product? And what tumor types are you going to be prioritizing?
Thank you for the question. Really, actually, very encouraging data from our perspective. We look at it from a breakdown in terms of the tumor types that were enrolled and the 2 that stood out from that program thus far.
Our non-small cell lung cancer, where you -- if you look at just the non-small cell lung cancer cohort, the overall response rate is about 31% with a very good durability. The 1 thing to note in that program is that responses do occur late -- so it's more of a long-term duration of control of these patients on the drug and most patients actually have disease control for a very long period.
As you saw, the duration of response is already 10.5 months. Then if you take about -- talk about the stable diseases as well, that also constitutes about the similar trajectory from our non-small cell lung cancer population. The second thing that was very encouraging was looking at the pancreatic cancer patient population and at the right doses at the 400 and 600-milligram dose, we saw actually increased response rates, again, a very good durability.
Some patients now going all the way almost up to a year. And so those 2 indications look very promising, and we are looking forward to giving you update on next year in terms of the later phase development for this program.
Next question will come from Steve Scala with Cowen.
I have 2 points and there are really -- 2 questions. They're just really clarifications but 1 percentage point of Bristol revenue growth is about $500 million. And that's the amount that Bristol is increasing its guidance that's roughly equivalent to what Revlimid So is the increase solely attributed to Revlimid?
And then secondly, and I apologize for going back to Asyndexian -- but the AFIP trial had a lower-than-expected event rate and failed. Why is a lower-than-expected event rate in the milvexian trial encouraging? It as easily could be a risk, I would think. I understand the DSMB point. So any clarity would be appreciated.
Thanks for the question, Steve. I'll ask David to start and then we'll flip over to Samit.
Yes, Steve, thanks for the question. And look, we saw a strong performance in our growth portfolio as we talked about. And that's why we also saw good performance and raised the Revlimid guidance to $5.5 billion, and that caused us to raise the full year outlook 5% growth versus prior year on a reported 6% excluding currency.
The other thing I would note, too, is as I said on the call, we have generic entry coming in on Sprycel Abraxane and POMALYST. The already facing generic as is POMALYST. So we just want to make sure that people update their models for the additional generic erosion in the fourth quarter. But net-net, when we put all that together, as we said, we raised our revenue guidance as a result.
And Steve, thank you. This is Samit. Great question. Just to recall, if you go back to study and we look at the event rate for then we look at the rate for apixaban. Apixaban was 1.03. Asyndexian was 2.33, if I remember, and even more so. And then if you think about what we have planned in the milvexian study is 1.33.
So overall, if you think about it, we are looking at a blended event rate as Chris mentioned, which is much lower than the planned event rate. So overall, we are encouraged by this and not necessarily thinking that it's an issue. As I said earlier, DMC continues to look at it, and they are okay with us continuing this study, and we are increasing the sample size.
Next question will come from Courtney Breen with Bernstein.
Another question just on the Covent launch. What I wanted to make sure we were able to understand is because some of the practicalities around kind of a patient receiving a script and kind of the doctor choosing that patient to prescribe to. Can you share some of the context on the warnings and precautions in the label, particularly around liver and how many patients you practically expect to be managed through these challenges. I do note that obviously, there isn't the box label warning, but there are some warnings that require extra physician attention. And so can you just speak to some of those challenges?
Courtney, thanks for the question. Just as you know, Kobani offers efficacy that at least as good or better than Zyprexa, without the significant adverse events that have plagued the dyslipidemia, EPS sedation, those are the ones where they lead to the greatest level of discontinuation and why you see patients stop treatment and physicians rechallenge with another agent.
We're very pleased with the label, and we're just at the beginning, but the progress and the feedback that we're hearing have been very, very positive. When you look at some of the monitoring that's in the label, remember, the large majority of patients have had recent lab assessments. So we don't anticipate this to be a barrier.
In the label, this is recommended. It's not a mandated and lab assessments are very common in this patient population. Most antipsychotics today recommend lab assessments. So we don't see it's an issue for adoption. And when you look at renal impairment in patients with schizophrenia, in the mid-single digits. So taken together, we are very pleased with the efficacy profile that is unique to based on its mechanism of action and its best-in-category safety profile.
And just to add to what Adam is saying. You will also see the data on longer-term studies, EMERGENT-4 and EMERGENT-5, hundreds of patients who have been treated through those as well. And the safety profile continues to remain the same, but certainly efficacy maintained. So that, in addition, gives us a lot of confidence in the overall profile for as Adam said.
Next question will come from Seamus Fernandez with Guggenheim Securities.
Wanted to just get a sense for your enthusiasm for the upcoming data at ACR for your CD19 asset? And how you see the evolution of a potential market for intensive immunologic treatments like this versus the potential for whether it be T cell engagers or bispecific products with a similar type target profile, but perhaps less efficacy.
And then just the second question is on the 2025 dynamics. Just hoping to get maybe a little bit of a better sense of the sort of pushes and pulls on IRA. I know you've said that you expect it to be largely neutral, but it does seem like there are opportunities to potentially increase volume in that context. And I just wanted to clarify whether or not any volume benefits are incorporated into your assumptions around that neutral assumption?
Samit, maybe you can start and then turn it over to Adam.
Thanks, Seamus. Great question. And let me start -- there are 2 parts on the drug side of things. Let's start with our cell therapies, truly a transformational approach to treatment of autoimmune diseases as we've seen with the emerging data from others -- and now we will have a chance to present our own data.
Just remember 1 thing. We just -- we started our study at the end of November last year. First patient was actually dosed in November of 2023. And so we are looking forward to presentation of that data -- there are a few things that you may want to notice as we present that data. Number one, who are the patients who are enrolled in these studies and what is the severity of the disease that they have been enrolled with.
And then secondly, after treatment, what happens to the B cell dynamics in terms of the loss of B cell or depletion of B cells as well as reemergence? And then what is the impact on their remission in terms of stopping the treatment that they were on for immunomodulators, immunosuppressants. And then, of course, what is the safety profile.
Remember, many of these patients will have underlying organ damage. And so that will be important to keep in mind as you look at the data. These are small number of patients, but we will be able to update these data again at ASH with additional patients, longer follow-up and even additional indications.
Second part of your question was around -- how do you see these as cost to T cell engagers bispecifics. I think that's an important element that we will need to consider and new publications have recently come out using BCMA-directed therapy, and there is a case report for CD19 directed T-cell engager as well in the past. And they look very promising, encouraging.
We'll have to see which patients should go on to car cell therapies in the future and which patients should go through with a T-cell engager and bispecifics because bispecifics will require repeated administration at a certain point in time, either weekly, by weekly or every 4 weeks. And we'll have to define then the duration of that treatment. So all of those questions are still to be answered for T cell engagers.
You recall we have a BCMA T cell engager that we stopped develop in multiple myeloma. But next year, in 2025, you will see a study -- a couple of studies starting in a couple of indications that we will certainly test out the theory for application of BCMA-directed bispecific in those diseases. Adam?
Yes. So just the question around the changes to the benefit design as it relates to IRA. So with the elimination of the coverage gap, we expect favorability with Eliquis next year due to redesign with the elimination of the coverage gap. But that's going to be offset largely by products like Revlimid and POMALYST in the catastrophic phase, where we're now responsible for 20%. So there are pushes and pulls with IRA opportunities, including patient affordability, also with changes in the Part D benefit design. But taken together, we see this as essentially net neutral across our portfolio.
The next question will come from Matt Phipps with William Blair.
Just wondering how you all view the market opportunity for the GPRC5D CAR-T maybe relative to Abecma, given you've now moved the 5D program into a second-line Phase II trial, do you think the profile is strong enough to really challenge a BCMA CAR-T? Or would it be used after a BCMA CAR-T.
And Chris, what type of are you going with tonight?
So we'll start with Adam, and Samit, you can chime in as well.
Yes. So, we started the study with our CPRC5D agent will be moving that quickly into Phase III registrational trials. We are very encouraged with what we've seen thus far. Remember, this is going to be an important asset that is going to be used after BCMA CAR-T treatment is a competitive environment we know. But with a single dose -- and the toxicity profile that we are seeing thus far with GPRC5D we think we have a really great opportunity here with this asset to be another leading cell therapy asset for our company.
Next question will come from David Risinger with Leerink Partners.
So I'll just keep it to 1 high-level question, please. So Chris, I think you mentioned a few times on the call that you see Bristol-Myers as a sustainable growth company. Could you just provide some more context on that, your sustainable growth expectations in light of 2026 revenue pressures and the end of the diabetes royalty stream. .
Thanks for the question, David. Yes. Look, as we have said consistently, our North Star since I took over as CEO in November has been that we execute in the short term and stay focused on building a company that will deliver long-term sustained growth and shareholder value, particularly as we work our way through the middle of the decade exiting with a very strong growth profile towards the end of the decade.
And as I think about the way that we continue to build confidence in that, I would say, I'd highlight 3 things. First, we have a young portfolio of growing assets. You've seen that in the quarterly results. And we're squarely focused on continuing to drive performance in this growth profile. We've got products like Cobenfi, which just launched very early in its life cycle.
Clearly, schizophrenia is important. You're going to see additional indications, notably the adjunctive indication in 2025. Breyanzi continues to show very solid and strong growth in cell therapy. And remember, that's at the tip of a pipeline of assets we've discussed this morning in fact, that look promising, including CD19 and GPRC5D.
We saw continued steady growth for Reblozyl and CAMZYOS. We would expect that to continue. Those 2 products have line extensions coming up in the next 12 months. And of course, we've talked considerably about Optulag and nivo subcu providing a foundation for our I-O business through the end of this decade and into the next.
And then when you step back from that, the second thing that's encouraging is we continue to see very good progress in our late-stage pipeline. We've talked about Novexion and the encouraging progress of that program in AFib as well as the 2 other additional indications we're running in parallel.
We're excited about LPA1. And remember, we have multiple Phase II programs that have demonstrated efficacy and safety for that program. So we're excited to see that play out. Ibertimide and mesignomide give us opportunities in multiple myeloma. And these are products that have important readouts over the next 12 to 24 months.
So we've got continued excitement in the late-stage pipeline. And then across all of our businesses, we've maintained financial discipline. That gives us the ability to have a solid balance sheet. Our P&L looks good, and that gives us strategic flexibility to continue to invest both in our internal program as well as source innovation externally as we did with the Karuna acquisition, for example, in December.
So if I add it up, I think those are the core components of how we continue to build conviction in the sustainable growth that we're looking to drive for the company.
Next question will come from Akash Tewari with Jefferies.
Given that there's been reports of J&J shutting down their cardiometabolic division, is there any potential for your team to renegotiate your partnership with them around and on subcu Opdivo, your team doesn't seem to be guiding for branded reps beyond the FDA regulatory protection which is a market contract to what Merck is communicating on subcu KEYTRUDA. Any color on why your team seems to be more conservative here?
So do you mind repeating the second question?
In terms of protections around subcu Opdivo in terms of the length of duration versus what Merck is communicating on subcu KEYTRUDA?
Got it. Sorry, we just missed that. So with respect to J&J, no change in our partnership with J&J. J&J has communicated, they continue to be squarely supportive and engaged on the milvexian program. And in fact, their work on the ongoing Phase III programs continues to be very, very good, and we've got a very good relationship with J&J on that program. And then Adam, I'll ask you to take the second.
Yes. Regarding the subcu. First, we look forward to the PDUFA date for the nivolumab subcu in late December. Launch planning is progressing very well. And we talked about shifting at least 30% to 40% of the total U.S. Opdivo business, we can do that ahead of the LOE, which is in late 2028.
As far as the extension of the I-O franchise. This is what excites us potentially about this product because not only does subcu address the treatment burden for patients and physicians with a 3- to 5-minute fusion time as well as in opposite injection what this is going to do based on the broad patent state for the subcu, it will allow us to extend our franchise into the next decade.
Next question will come from James Shin with Deutsche Bank. .
I just want to go back to milvexian real quick. I really appreciate the update on the stroke and embolism event rates. But was there any separation between the arms? And perhaps even more importantly, do you have any color on bleed rates.
Thank you, James, for the question. Obviously, we can't look at those from a by-arm perspective. This is a blinded study. We don't get to see the data that way. It's a blended event rate that we can talk about and we don't get to the specifics of the general profile of the drug at this time. .
Next question will come from Olivia Brayer with Cancer.
Can you guys talk through what you're looking to see in that adjunctive because for any data set next year? And when you think about uptake in that setting, are you getting any early feedback around potential off-label use from potential early adopters? I mean how big of a market do you think that could realistically be just given the focus on making monotherapy use a standard of care. Also, I just wanted to ask a quick clarification on milvexian time lines. I know it's still 2027, but should we assume that it's later in the year considering today's update?
Thanks for the questions, Olivia. Maybe we'll ask Samit and Adam to get those questions between the 3 of them.
Yes. Thank you. Remember, Olivia, how patients are treated today. with the antipsychotics that are available without even having an approval in the label, patients are being treated with combinations of D2 agonist in this space. So it was important from our perspective to generate the data to showcase efficacy as well as the safety profile of combining muscularis with the background therapies that patients are on.
And that's the intent of showing the -- from the ARISE program perspective as an adjunctive therapy, what Coventry can deliver on top of the background therapies. That will be important, and that study will read out in 2025. On milvexian side, from a clarification perspective, the 2027 is an event-driven end point in the trial.
So we can't give you a specific in terms of the timing within 2027. That's why we give you a general guidance for 2027 as before.
Olivia, thanks. As it relates to adjunctive commercially today, use to 2 D2s to get greater efficacy and around 20% to 30% of the patients, even though the D2s are not FDA approved for adjunctive treatment, we do believe that could be an important adjunctive treatment option. Samit talked about the ARISE study, and we're working to generate evidence on this.
And pharmacologically, it makes sense adding an M1 and 4 on top of a D2 because, again, we think there could be synergistic effects there. So we're excited to see the study readout. Just to be clear, though, our teams are focused on driving on-label use in schizophrenia to make fee standard of care there. And we can't -- it's not going to be our choice, but patients may or may not choose to use Cobenfi off-label because of the safety profile of the product. But we're really excited for the data readout next year in Juno schizophrenia as well as some of the other data readout that Samit talked about how phymerpsychosis, these are going to be important accelerators of growth for this product.
And I would just remind you what Adam ended on is really important, which is that -- this is a product that, obviously, we're super excited about the initial indication in schizophrenia. We've got the adjunctive data coming, but this is a product that will continue to generate new line extensions with a very robust clinical development plan that we put in place for it.
Next question will come from Sean McCutchen with Raymond James.
One more on Can you speak to your view on the import of the M1 component for as it relates to potentially driving targeted improvements in particular, what proportion of the population have cognitive deficits. Do you expect these patients to be kind of parsed out in the monotherapy setting or post atypical or in the setting?
And what are your comments to those that are looking at the BID regimen and GI adverse effects as potential barriers on ease of use in this patient population where compliance or lack thereof is a significant variable when thinking about your competitors that are coming up behind you.
Samit will take the first part and then Adam.
Yes. Thank you. Remember, the differentiating feature for Covent is that it's a dual direct agonist as opposed to some of the other therapies in development that target the M4 to indirect ways because they are allosteric modulators, which require a ligand such as to be present in the brain.
And M1 is a very important component because from a biological perspective, that is associated with cognition function in the brain. And so having a direct impact on M1 as well as M4 gives us that opportunity to really impact the cognition -- and during the overall life cycle, as we think about the Alzheimer's disease patients as they go through it, cognition does become important in terms of the impact on the patient and patient life and quality of life.
So there's a large proportion of patients who will have cognitive impairment and will be eligible if the data reads out positive to be treated with the drug. So overall, that's why we've developed a program in all 3 parts of AD that impact from a psychosis perspective, agitation perspective as well as recognition perspective. Adam?
Yes. So it relates to the dosing regimen for that step back and just talk about the leading cause of discontinuation. Number 1 is efficacy and cobenfi delivers unsurpassed efficacy, efficacy that's at least as good as a -- and the other areas of high-level discontinuation include areas like weight gain, include dysfunction, trouble concentrating, excessive sedation. And so now physicians don't need to trade that off. People living with schizophrenia commonly managed multiple medications at significantly higher rates than the general population.
In fact, when you look at patients with schizophrenia, they're on average 7 pills a day which includes our antipsychotic. It could include different psychotropic medications, including anti-depressants, anti-anxiety medications as well as medicines to combat the adverse events of their existing products. So yes, we're going to need to manage this, but we don't believe that this will impact uptake based on the unprecedented efficacy that has shown.
Last thing I'd mention is we saw very low discontinuation rates in our clinical trial due to the fact that patients that robust efficacy that the product is well tolerated and we will provide support to both patients and caregivers to maximize compliance with times.
I know you all have a busy morning in the space. So we'll take our last question, and then we'll turn it to Chris for some brief closing remarks.
The last question will come from Crypta Devarakonda with Truist Securities. .
Congrats on the quarter today. I'll switch gears and not ask a question. I want to ask a question about your test program. You've recently published data from a Phase II with mavacamten. Can you talk about how this translates to 2 to 4, which I think is the drug you've indicated as the PPAP drug? And what percentage -- like how big of a market do you see? And can you remind us of the time lines for this program?
Thank you, for the question. HFPEF is an important indication. We've always indicated that as we think about myosyncartic inhibitors, with the impact that it does have on the cardiac function and remodeling in general, there is an important element that we wanted to test out, which we first tested out with mavacamten in a small number of patients, which gave us an inkling into the -- through the biomarker work that we did over there through anti-proBNP as well as on measurement, which gives us confidence to continue with that program.
We switched over to MYK-224, which was the second program that was available to us, and that's the beauty of having 2 cardiac myosin inhibitors in the programs. And -- that trial is enrolling very well. We are now extending that trial in terms of the Phase IIa study to enroll more patients to generate the data. We anticipate that, that Phase II data readout in the next couple of years and then start the Phase III program based on the doses that we have identified in that Phase II program.
And then in the early part of next decade is when we anticipate to really have the Phase IIIs reading out. We don't have a time line specifically in terms of the year -- but really excited to see what we have seen thus far and looking forward to initiation.
Yes. As far as the opportunity, this is a large opportunity where heat affects around 3 million people in the United States and that is expected to grow significantly over the course of the decade. In fact, the heart failure drugs, the category is valued at over $12 billion in 2022, and we expect this to almost double by 2032. So this is a significant opportunity, and we're really pleased with what we're seeing early on with.
Thanks, Adam. Well, thanks, everyone, for joining us for the call today and for the very thoughtful questions. Maybe I'll just leave you with a few thoughts on the performance for the quarter.
First, as you hopefully have gotten from the discussion, we remain very focused on execution. The growth portfolio is now, as David mentioned, contributing nearly half of our total revenue -- and that profile continues to benefit from robust demand for key products, products like Reblozyl, Breyanzi, and Second, the Covinfi approval is a pivotal achievement. We've been working hard to deliver that since we closed the Karuna transaction.
And this is an important medicine for patients, and it's an important growth driver for the portfolio. Third, we continue to advance our innovative pipeline across therapeutic areas. We've had several important readouts over the course of the year, and we have a few more coming between now and the end of the year as well as beginning of next year.
And then finally, again, as you hopefully gathered, our commitment to operational excellence is yielding results, and we're going to remain focused on driving value across the organization. So thanks again for your time today. And as always, the team is available for follow-up questions, and have a great rest of the day.
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