Eli Lilly and Company (NYSE:LLY) Q4 2024 Results Conference Call February 6, 2025 10:00 AM ET

Company Participants

Mike Czapar - Senior Vice President of Investor Relations
David Ricks - Chair and CEO
Lucas Montarce - Chief Financial Officer
Dr. Dan Skovronsky - Chief Scientific Officer & President of Lilly Immunology
Patrik Jonsson - President of Lilly Cardiometabolic Health & Lilly USA
Dave Hyman - Chief Medical Officer
Anne White - President of Lilly Neuroscience
Jake Van Naarden - President of Lilly Oncology
Ilya Yuffa - President of Lilly International
Marc Kemen - Investor Relations
Wes Taul - Investor Relations
Wai Wong - Investor Relations

Conference Call Participants

Tim Anderson - Bank of America
Terence Flynn - Morgan Stanley
Courtney Breen - Bernstein
Chris Schott - JPMorgan
Geoff Meacham - Citibank
Colleen Garvey - Guggenheim Securities
Conor MacKay - BMO Capital Markets
Umer Raffat - Evercore
Steve Scala - TD Cowen
Mohit Bansal - Wells Fargo
Dave Risinger - Leerink Partners
Akash Tewari - Jefferies
Alexandria Hammond - Wolfe Research
Chris Shibutani - Goldman Sachs
James Shin - Deutsche Bank
Trung Huynh - UBS
Nicole Germino - Truist Securities

Operator

Ladies and gentlemen, thank you for standing by, and welcome to the Lilly Q4 2024 Earnings Call. [Operator Instructions] I would now like to turn the conference over to your host, Mike Czapar, Senior Vice President of Investor Relations. Mike, please go ahead.

Mike Czapar

Good morning. Thank you for joining us for Eli Lilly and Company's Q4 2024 Earnings Call. I'm Mike Czapar, Senior Vice President of Investor Relations.

Joining me on today's call are Dave Ricks, Lilly's Chair and CEO; Dr. . Dan Skovronsky, Chief Scientific Officer and President of Lilly Immunology; Lucas Montarce, Chief Financial Officer; Anne White, President of Lilly Neuroscience; Ilya Yuffa, President of Lilly International; Jake Van Naarden, President of Lilly Oncology; and Patrik Jonsson, President of Lilly Cardiometabolic Health and Lilly USA. We're also joined by Mark Keman, Wes Tall and Wai Wong of the Investor Relations team.

During the call, we anticipate making projections and forward-looking statements based on our current expectations. Our actual results could differ materially due to several factors, including those listed on Slide 4. Additional information concerning factors that could cause actual results to differ materially is contained in our latest Form 10-K and subsequent filings with the SEC.

The information we provide about our products and pipeline is for the benefit of the investment community. It is not intended to be promotional and is not sufficient for prescribing decisions. As we transition to our prepared remarks, please note that our commentary will focus on our non-GAAP financial measures.

Now, I'll turn the call over to Dave.

David Ricks

Okay. Thanks, Mike. 2024 was a productive year for Lilly.

We grew our top line, advanced our pipeline and invested in our supply chain to meet the increasing demand for our medicines. Most importantly, we delivered for patients by bringing life-changing medicines to more people around the world. In 2024, full year revenue grew 32% compared to 2023, exceeding our first-time guidance by $4 billion.

Revenue grew 45% in the most recent quarter as our recently launched products gained momentum. Last year, we announced positive Phase III results for imlunestrant, insulin efsitora alfa and 3 additional tirzepatide trials. We also started Phase III programs for lepodisiran, remternetug and olomorasib based on positive earlier phase data.

We continue to complement our pipeline through acquisitions and collaborations. We acquired Morphic Therapeutics and announced a collaboration with OpenAI to invent novel antimicrobials. We opened the Lilly Seaport Innovation Center in Boston as a hub for Lilly's genetic medicines efforts and announced a new Lilly Gateway lab in the U.K. to collaborate with European research.

We advanced our manufacturing agenda, announcing investments to expand our footprint in Indiana, in Wisconsin and in Ireland. Since 2020, our commitments to build, expand and acquire manufacturing facilities now total more than $23 billion. Importantly, we brought innovative new medicines to patients.

In 2024, we received regulatory approvals for Kisunla, Ebglyss, and a new indication for Zepbound in OSA. This progress strengthens our portfolio of new products and enhances our capacity to drive top-tier growth and margin expansion. As you can see on Slide 5, we continue to make progress against our strategic deliverables in Q4.

Revenue grew 45% and our new products growing by more than $3.1% billion, led by a strong uptake of Mounjaro and Zepbound. Q4 also saw a solid performance across oncology, immunology and neuroscience. Our business, excluding incretins, grew by 20% in the quarter compared to Q4 2023, excluding the onetime benefits of business development.

Since our last earnings call, we achieved several key pipeline milestones. We received approval for a new indication of Zepbound and Omvoh. We submitted imlunestrant for metastatic breast cancer and tirzepatide for heart failure.

We also announced positive Phase III results in the SURMOUNT-5 study, where Zepbound demonstrated a 47% greater relative weight loss compared to Wegovy. We strengthened our overall supply position and delivered on our production target to make 1.5%x the salable doses of incretin medicines in the second half of '24 compared to the second half of '23. With more patients using Lilly Direct, the uptake of single-use Zepbound vials increased.

We had no wholesaler back orders as we closed 2024, and wholesalers have been fulfilling orders from pharmacies at very high levels. We continue to augment our internal pipeline with external innovation, announcing plans to acquire Scorpion Therapeutics' mutant-selective PI3Ka inhibitor program. This transaction will add a clinical stage breast cancer asset to our oncology pipeline.

And lastly, we returned $3 billion to shareholders via dividends and share repurchases. In addition to that, we announced at the end of the year a $15 billion share repurchase program and the seventh consecutive 15% increase in our quarterly dividend. On Slide 6, you'll see a full list of key events since our Q3 call, including the milestones I mentioned here and several other updates.

Now I'd like to turn the call over to Lucas to review our Q4 and 2024 full year results and provide details on the '25 guidance.

Lucas Montarce

Thanks, Dave. Slide 7 summarizes our financial performance in the fourth quarter and Slide 8 for the full year. As Dave mentioned, our revenue grew 45% in Q4, primarily driven by Mounjaro and Zepbound.

Performance of our non-incretin portfolio was also strong as revenue grew 20%, excluding onetime payments related to business development. Gross margin as a percentage of revenue increased to 83.2% in Q4, primarily impacted by favorable product mix. R&D expenses increased 18% from continued investment in our early and late-stage portfolio.

In total, we started 8 new Phase III programs in 2024 and advanced several new assets into the clinic. Marketing, selling and administrative expenses increased 26%, mainly driven by promotional efforts to support ongoing and future launches. This includes U.S. direct-to-consumer advertising on Zepbound and Mounjaro and U.S. launch activities for Kisunla and Ebglyss.

We also increased our commercial investment outside the U.S. to support international launches of Mounjaro. Operating income more than doubled, increasing to $5.6% billion, driven by higher revenue from new products. The effective tax rate was 13.2%.

We delivered earnings per share of $5.32%, inclusive of $0.19% of acquired IPR&D charges. This compares to $2.49% in Q4 2023 that includes $0.62% of acquired IPR&D. On Slide 9, we quantify the effect of price, rate and volume on revenue growth.

U.S. revenue increased 40% in Q4, driven by robust volume growth of 45%. Zepbound and Mounjaro were again the largest growth contributors, partially offset by declines in Trulicity. Realized prices decreased 5% in the U.S. due to favorable changes to estimate for rebates and discounts related to Mounjaro in Q4 2023.

Europe revenue grew 82% in constant currency. We continue to be pleased with the uptake of Mounjaro and have now launched in all major European markets. In addition to growth from Mounjaro, European revenue benefited from onetime payment associated with the amendment of our alliance with Boehringer Ingelheim.

This was recorded in Jardiance's revenue in Q4. Excluding this onetime payment, Europe revenue grew 61%. Japan revenue grew 27% in constant currency.

Volume growth was driven by Mounjaro, Omvoh, Jardiance and Verzenio. In China, revenue increased 13% in constant currency. Tyvyt and Verzenio drove volume growth.

Mounjaro was recently made available in China and will proceed with a limited launch as supply becomes available. We expect modest initial Mounjaro sales in China due to supply limitations, a more meaningful contribution in the second half of 2025. Revenue in the rest of the world grew 46% in constant currency, driven by volume growth of Mounjaro and Verzenio.

Slide 10 provides an update on our performance of new and growth products. New products more than doubled in Q4 to $5.6% billion, led by global Mounjaro sales of $3.5% billion and U.S. Zepbound sales of $1.9% billion. U.S. Zepbound performance is going very well.

We began promotional activities this quarter, and we continue to see strong uptake. In Q4, Zepbound became the market leader in the anti-obesity market as measured by new prescriptions. As shown on slide 11, we combined U.S. incretin analog market, grew 45% compared to Q4 2023.

We increased 3 percentage points in share of market in Q4 2024. Jaypirca worldwide revenue was $114 million, adding another solid quarter of sequential revenue growth. Worldwide Omvoh revenue increased to $57 million.

With the recent FDA approval in Crohn's disease, we look to drive broader use in an additional patient population. The Kisunla launch is progressing well and prescriptions in the U.S. have been steadily increasing. While it is early, we saw positive momentum across key indications -- key indicators, including volume of diagnostic ordered, access in priority integrated health systems, coverage by Medicare and commercial plans and number of infusion sites placing orders.

We are encouraged by the launch of Ebglyss in the U.S. We saw early positive receptivity and high levels of physician engagement. In addition, we expect commercial access with 2 of the largest pharma benefit managers beginning in March. We now plan on accelerating investment in commercial activities to drive new patient start.

Growth products also performed well as revenue increased by 13% compared to Q4 2023. Verzenio's growth trajectory continued as U.S. total prescription grew by 15%. In addition to strong execution in the early breast cancer indication, Verzenio revenue benefited from increased U.S. wholesaler stocking at year-end.

Worldwide Trulicity revenue declined 25%, driven by Mounjaro switches and to a lesser extent, lower realized prices. On Slide 12, we provide an update on capital allocation. Moving to Slide 13 and 14, I will discuss our 2025 financial guidance.

As previously shared, we expect 2025 revenue to be between $58 million and $61 billion. The midpoint represents approximately 32% growth compared to 2024. We anticipate continued U.S. incretin class growth, consistent with the trajectory of total prescriptions seen in 2024.

We expect to launch Mounjaro in new markets outside the U.S. and Europe throughout the year. Mounjaro international revenue will contribute to overall performance more significantly in the second part of 2025. Given the uptake of newer incretins, we expect Trulicity volume to continue declining as fewer new patients are starting on Trulicity.

We expect oncology, neuroscience and immunology to also grow revenue in 2025 as Ebglyss, Jaypirca, Omvoh and Kisunla launch upticks continue. At the portfolio level, we anticipate foreign exchange to be a headwind as the dollar has strengthened relative to other currencies. In addition, we forecast overall net prices to decline by mid- to high single digits in percentage terms, including U.S. Part D changes.

We continue expanding our manufacturing capacity and estimate to produce 1.6%x the amount of incretin salable doses during the first half of 2025 compared to the first half of 2024. Our facility in Concord is anticipated to begin shipping medicines this year, and we plan to make continued progress on expanding our manufacturing network. Our expected ratio of gross margin less OpEx divided by revenue is expected to be between 41.5% and 43.5%.

At the midpoint, this reflects approximately 340 basis points of margin expansion compared to 2024. In SG&A, we will continue to invest behind our new launches, including direct-to-consumer efforts in the U.S. to drive new patient activation. In addition, we plan to increase investment outside the U.S. to support the launches of Mounjaro in new and existing markets. In R&D, we plan to accelerate our investment in early and late-stage activities.

As Dan will share later, we started 8 new Phase III programs in 2024 and anticipate that investment in those programs will ramp as the studies enroll patients. We also plan to initiate new Phase III programs in 2025. While we keep a high bar for what we advance into clinical trial development, we expect to scale our investment in R&D this year.

Other expenses is expected to be $600 million to $700 million, driven by interest expense. We estimate our effective tax rate to be approximately 16%. Earnings per share or EPS is expected to be $22.50% and $24 on a non-GAAP basis.

This doesn't include a forecast for charges related to IPR&D. Now I will turn the call over to Dan to highlight our progress in R&D and to provide an overview of potential key events we expect in 2025.

Daniel Skovronsky

Thanks, Lucas. Lilly R&D had another productive quarter. I'll cover pipeline progress in Q4, then the 2024 key events and finally, provide potential key events for 2025.

Since our last earnings call, 2 new indications were approved in the U.S., Zepbound for obstructive sleep apnea in adults with obesity and Omvoh for moderate to severe Crohn's disease. Both approvals are important milestones and mark an expansion in the number of patients who can benefit from each of these medicines. Moving to regulatory submissions.

We completed submissions in the U.S. and EU for tirzepatide for heart failure and global submissions for imlunestrant for metastatic breast cancer and for Jaypirca with the BRUIN CLL-321 data. I'm also pleased to share that we've submitted an update to the Kisunla U.S. label to include the dosing modification data from TRAILBLAZER-ALZ 6, and the FDA has granted the submission a priority review. In our Phase III portfolio, we initiated a new program for Orforglipron in obstructive sleep apnea.

This program includes 2 studies under the same master protocol to evaluate if people with obstructive sleep apnea and obesity can benefit from Orforglipron. After Zepbound was approved in the U.S. as the first and only prescription medicine for obstructive sleep apnea, we're excited to explore if an oral GLP-1 can also deliver a benefit in this disease. Earlier in the pipeline, we advanced the second oral GLP-1 into Phase II in obesity and advanced Eltrekibart into Phase II for ulcerative colitis.

Three Phase II assets and 1 Phase I asset have been discontinued based on clinical readouts. In Q4, we also began Phase I studies for 4 new molecules, 1 in each of our therapeutic areas. Q4 capped off a productive year of advancing new medicines at Lilly.

In total, over the year, we started 8 new Phase III programs. We disclosed Phase III data from 21 trials, including 17 major publications in top-tier medical journals. We received regulatory approvals for 2 new medicines, Ebglyss and Kisunla as well as many new indications around the world.

And we added 14 new programs to the early phase pipeline. On Slide 16, we detail these outcomes for our 2024 milestones. I'm pleased that nearly all of our anticipated milestones came to fruition positively in 2024.

Turning our focus to 2025. Slide 17 shows key R&D milestones we expect this year. Starting with our late-stage portfolio, we expect to initiate 2 new Phase III programs this year.

First, in oncology, we'll begin an adjuvant non-small cell lung cancer Phase III program for our KRAS G12C inhibitor, olomorasib, building on its ability to be administered with immunotherapy. Our current metastatic program is progressing well, and we've aligned with the FDA on our Phase III dose through the Project Optimus pathway. We shared a clinical update at the World Conference on Lung Cancer last fall, and we are encouraged by the ability to safely combine olomorasib with other agents.

Our new Phase III program will focus on moving to an earlier setting and combining with existing approved agents in both resectable and unresectable KRAS G12C mutant lung cancer to prevent cancer from recurring. The second program is in cardiometabolic health, where we plan to initiate a Phase III trial for Orforglipron in hypertension, adding to the ongoing trials in type 2 diabetes, obesity and obstructive sleep apnea. I'm excited that this year, we're looking forward to reading out multiple Orforglipron trials.

We expect to see data from up to 5 studies in type 2 diabetes and 2 studies in obesity. Our goal is to generate efficacy, safety and tolerability profile that is similar to that of an injectable single-acting GLP-1, but through an orally available medicine. The first Orforglipron Phase III trial to read out will be ACHIEVE-1, which is a 40-week study in patients with type 2 diabetes.

These patients have a baseline hemoglobin A1c between 7% and 9.5% and a body mass index of 23 or greater. The trial utilizes 6 escalating doses in 4-week increments to a maximum dose of 36 milligrams. Based on prior studies of Orforglipron as well as other GLP-1 therapies, we expect weight loss in people with diabetes to be significantly less than in people living with obesity who do not have diabetes.

We anticipate ACHIEVE-1 will read out in Q2 this year, followed by up to 4 additional type 2 diabetes trials in the second half of 2025 and a potential submission for this indication in 2026. The Orforglipron Phase III trials in people with obesity, ATTAIN-1 and ATTAIN-2 are expected to read out in Q3 of this year. These trials will form the basis of our first Orforglipron regulatory submissions, which will be for the treatment of obesity, and we expect to occur late in 2025.

This year, we also expect data from the tirzepatide cardiovascular outcome study SURPASS-CVOT. Of course, this is an event-based trial, and the time line is dependent on the accrual of cardiovascular events. We anticipate data in Q3.

While designed to measure both non-inferiority and superiority compared to Trulicity, a positive outcome in either would demonstrate that tirzepatide reduces the risk of cardiovascular outcomes and would support a labeled indication. Late this year, we expect to see the first data from our triple-acting incretin Retatrutide which combines GLP-1, GIP and glucagon. We believe this potential new medicine can deliver even more weight loss than tirzepatide and could potentially provide additional health benefits.

The initial study to read out TRIUMPH-4 is a 68-week study in patients with osteoarthritis of the knee who have a body mass index of 27 or greater. We'll also see multiple additional Jaypirca data sets this year. Physician feedback is very positive on experience with Jaypirca in the currently approved indications, and we hope that generating data in earlier lines of therapy will enable broader use within CLL and MCL.

We could see data from additional trials in the first-line or BTK-naive settings this year. Moving to neurodegeneration. While we don't have a key event listed in 2025 for donanemab, we're closely watching the preclinical Alzheimer's disease study, TRAILBLAZER-ALZ 3.

This trial screened patients with a blood-based diagnostic and utilized a fixed duration of treatment with donanemab. By moving earlier in disease progression, the goal is to reduce the risks of developing any symptoms of Alzheimer's disease. While the current primary completion is projected for 2027, the study will read out when the target number of progression events are accrued.

A new focus area for us in 2025 will be to study potential new applications of incretin biology across diseases in neuroscience and immunology. With the pipeline of incretins in clinical development and deep scientific expertise in this space, Lilly is well positioned to match the biologic properties of specific molecules to the desired indications being studied. We plan to start several clinical trials, assessing potential benefits of our incretins in areas that could include brain health, substance use disorder, pain, neuropsychiatry and inflammation.

We'll be prepared to move rapidly into Phase III trials based on clinical data and where our conviction is high. Lastly, we expect a number of important regulatory submissions in 2025, including Orforglipron for obesity, as I detailed, insulin efsitora alfa for type 2 diabetes, tirzepatide for cardiovascular outcomes and multiple potential data sets for Jaypirca. 2025 will be another exciting year for Lilly R&D.

Now I'll turn the call back to Dave for some closing remarks.

David Ricks

Yes. Thanks, Dan. So we had a strong financial performance in Q4 and throughout 2024.

We finished $4 billion above our first-time revenue guide and $4 per share above our first-time EPS guide when taking IPR&D charges into account. The incretin market continues to grow rapidly, and Mounjaro and Zepbound are both gaining share of market. We believe both products are still very early in their launch cycle.

In addition, our oncology, immunology and neuroscience therapeutic areas continue to progress, launching new medicines and delivering strong revenue growth. We have an exciting outlook for growth in 2025 as well. New indications, new manufacturing capacities, new access opportunities and new markets are all tailwinds to our financial performance.

We made significant advances across our pipeline in 2024 and have several exciting readouts, which Dan just highlighted, expected throughout 2025. So now let me turn the call over to Mike to moderate our Q&A session.

Mike Czapar

Thanks, Dave. We'd like to take questions from as many callers as possible and conclude our call on time. So to that end, consistent with prior quarters, we will respond to one question per caller, and we will end at 11 a.

m. [Operator Instructions] Paul, please provide the instructions for the Q&A, and we're ready to take the first caller.

Operator

[Operator Instructions] And the first question today is coming from Tim Anderson from Bank of America.

Timothy Anderson

Just a question on the guidance, the 2025 guidance. So I think everyone knows the prescription uptake trend didn't show acceleration, hasn't shown it yet. That's been viewed by some as a concern.

Does the 2025 guidance require acceleration. Or can you get the scripts just continue on the same trajectory and the slope of that line doesn't change. When I do back of the envelope math, it seems like that's frankly all that needs to occur.

And one of your slides suggests that might be the right way to think about it as well, but can you just confirm.

David Ricks

Great. Thanks, Tim, for the question. We'll go to Lucas to talk about the guidance assumptions.

Lucas Montarce

Yes. We mentioned in my notes that what we expect to see, Tim, is a continuation of basically the total prescription growth that we have seen in 2024. So that's what we built in our 2025 guide.

David Ricks

To the market.

Lucas Montarce

For the market, yes.

Operator

The next question is coming from Terence Flynn from Morgan Stanley.

Terence Flynn

I was just wondering if you could maybe elaborate on your expectations for Zepbound payer dynamics and access this year, particularly the impact from the OSA label. I know you've also filed for heart failure and how you expect that to play out over the course of the year. And then anything on next steps on the compounding litigation that we should be focused on.

David Ricks

Dangerously close to a 2-part question there, Terence, but we'll go to Patrik to talk about access, and then I'll come back to Dan to make a quick comment about compounding.

Patrik Jonsson

Thank you very much. When we look at the commercial access, it remains strong. We have 8% to 7% coverage in the commercial space still.

And of course, the employer opt-in is a second step of high importance that made progress in 2024, and we expect in terms of employer opt-in that we are north of 50% today. OSA remains an opportunity for us to gain access also in the Medicare segment, and CMS confirmed recently that they will reimburse OSA if Plan D plans decides to lift it. And they have 180 days to make that decision from the FDA approval, and we're working with plans right now, and we anticipate to get some Medicare coverage by the second half of this year.

And similarly, OSA is also an opportunity for us to get more Medicaid states signed in. We expect PIF when and if approved, to have a similar role as OSA, an access opportunity, particularly in Medicare and Medicaid.

Daniel Skovronsky

Yes. So regarding compounding, I think our position has been pretty clear. We've been in supply since August and FDA took us off the list formally later in Q4.

Of course, the compounding associations are suing to delay that. We opposed that and joined that suit. I think the next date coming up is February 18, where the FDA said that's when you need to stop one form of compounding.

Our position has been clear all along. We don't think there's a place for this because we have full supply, and there's no reason to have non-approved kind of illegitimate product out there. So of course, new sheriff in town, new government and court case pending.

So we don't know the outcome of all that. But that all said, I mean, I think our business is growing nicely in Q4, and we can see that in prescription trends early this year. It's just an unsafe practice that shouldn't exist and long term probably isn't great for innovators.

So we'd like to move on from this and hope that's what the courts and the government decide to do.

Operator

The next question is coming from Courtney Breen from Bernstein.

Courtney Breen

I just wanted to zoom into Orforglipron specifically, and I think you made -- took the chance to make the point about diabetes and diabetes population and their weight loss. Can you just talk a little bit more about kind of the potential positioning, particularly in the context of kind of that single injectable GLP-1 kind of anticipated efficacy that you're guiding to.

David Ricks

Great. Thanks, Courtney. We'll go to Dan to talk about the right comp for Orforglipron.

Daniel Skovronsky

Yes, sure. I'll start on the efficacy expectations and then maybe Patrik can talk about the market positioning here. So you're right, it's a single GLP-1, and we take pains to mention that because we're not expecting the kinds of efficacy or tolerability actually that we see with tirzepatide, which is a dual-acting agent.

Still, as you know, monotherapy with GLP-1 has provided important benefits to many patients. And so we're setting our sights there. This is a first study in type 2 diabetes patients where, as I noted, weight loss is typically quite a bit lower than you see in people without type 2 diabetes.

So we sort of index on the efficacy that we've seen in the past with Ozempic, and we'll get that data soon and excited to see it. Patrik.

Patrik Jonsson

And from a positioning perspective, we like the idea of having an oral with an injectable GLP-1 like efficacy. And there is a big portion of patients that actually have needle fear. It's estimated in the U.S. to be 20% to 25% and also a group of patients that doesn't necessarily need the amount of weight loss or HbA1c reduction as tirzepatide generates.

And that might be an opportunity in the maintenance space as well. But lastly and very importantly, it's an opportunity to scale in markets outside the U.S., taking into account that we don't have a need for refrigeration.

Operator

The next question is coming from Chris Schott from JPMorgan.

Christopher Schott

Just another Orforglipron question. You've now launched a pretty wide range of studies, I guess, to say hypertension beyond the initial obesity and type 2 diabetes studies. Can you just elaborate a little bit more on what gives you confidence in running such a wide range of programs without having seen those initial readouts, particularly maybe some of the tolerability profiles with the drugs titration, et cetera.

I'm just trying to think how you balance kind of the risk taking there with the confidence in the asset you have right now.

David Ricks

Great. Thanks, Chris. We'll go to Dan for that question.

Daniel Skovronsky

Yes. Thanks, Chris. It's a smart question.

Of course, going into Phase III with any drug, particularly a small molecule such as Orforglipron, the biggest risk is safety. And I think as these trials proceed, even though we're not seeing the safety data, we grow more confident in the overall safety profile of the drug because the trials continue uninterrupted. Of course, we won't know for sure until we get that first data readout and then subsequent data readouts.

But it's correct that we grow more and more confident in the success of this molecule as each day passes. As for specifics around tolerability and titration and discontinuations, those don't really factor into our thinking. We haven't had a look at unblinded data for any of those things.

So we can't make assumptions on that yet.

Operator

The next question will be from Geoff Meacham from Citibank.

Geoffrey Meacham

Just had one on commercial tirzepatide in bigger settings like diabetes prevention or if the SURPASS-CVOT is successful. Would these be a tipping point on broader reimbursement or access. I mean it's clear you have a benefit there, but I wasn't sure if commercial payers or Medicare are looking for yet even more data to support kind of risk benefit.

David Ricks

Great. Thanks, Geoff. We'll go to Patrik to talk about the broader landscape there.

Patrik Jonsson

Thank you very much, Geoff. I think the SURMOUNT-1 extension is definitely defined as game-changing at the provider level, and we are in discussions, of course, with regulatory agencies. But there is no precedent for type 2 prevention as an indication.

But the data itself, I think we will utilize to really drive increased employer opt-in seeing the benefits of outcome studies and treatment of people with prediabetes and obesity.

Daniel Skovronsky

Maybe just a broader point, which we've said before, Geoff, I think a lot of investors are looking for some single event that will trigger the broad reimbursement or not. And I don't think we've ever really thought of it that way, but rather an accumulation and sort of weight of everything that will grow reimbursement steadily over time. And I think that's actually what we've seen since we launched Zepbound last year, U.S. commercial insurance picking up several points during the year and even ex U.S. now with U.K. reimbursement, et cetera.

Different payers will make different decisions at different times. And I think the data sets you mentioned will be some of the more compelling to create moves, but still then the way affordability and budget constraints, et cetera. That all said, by the time we get to the end of the decade, it's hard to imagine we are not using obesity medications to prevent what is the precursor condition to so many chronic diseases.

And already, the health economics are pretty compelling, and there'll be more data coming beyond that. So long term, we remain really, really bullish on this whole category being reimbursed like we expect to reimburse all other medications. Just the schedule for that is going to be more slow and steady, I would say, as you model expectations on a global scale and in the U.S. as well because of the diversity of the payers.

Operator

The next question will be from Seamus Fernandez from Guggenheim Securities.

Colleen Garvey

This is Colleen on for Seamus. We just wanted to ask on the sustainability of operating margin expansions. Looking at some of the longer-term forecasting from sell-side consensus, we're seeing estimates nearing 50% by the end of the decade.

Do you view this as realistic. Or how are you thinking about the balance between the margins and then also ensuring you're not underinvestigating on the pipeline.

David Ricks

Great. Thanks for the question, Colleen. I'll go to Lucas to talk about the long-term operating margin philosophy.

Lucas Montarce

Well, we are very pleased with the results that we've seen in 2024 and Q4, and we provided a guidance for 2025 that is a continuation of that margin expansion with -- I mentioned 340 basis points expansion in 2025. Thinking more long term, our view is how we continue to drive growth in a sustainable manner. And in order to do so, we believe that reinvesting into the business, in particular, in R&D to drive that innovation and growth into the future is critical success factor for our business. So from that perspective, we mentioned before that we believe that getting into high 40s or 50% is not actually a good way to drive that sustainable growth into the future.

So what we are seeing now on that low 40s is, in particular, at this time, the right basically balance that we have in terms of investment into the business and also the returns that we generate as well.

Operator

The next question will be from Evan Seigerman from BMO Capital Markets.

Conor MacKay

This is Conor MacKay on for Evan. Given some of the slower launches we've seen from peers in the Alzheimer's space, can you maybe talk a bit about the lessons you've taken from those and then as well as sort of your experience early days in the Kisunla launch.

David Ricks

Great. Thanks, Conor, for the question. We'll go to Anne to talk about Kisunla.

Anne White

Well, thanks so much for the question about Kisunla. And I'll tell you, we are pleased with our momentum so far. What our system -- our team is focused on really is system readiness and growth.

That's still a significant area of opportunity in the space. So we're partnering with health care providers to scale and reach more patients. As far as how it's going so far, Lucas mentioned key indicators that we're watching.

To date, we've achieved P&T approvals of over 80% in our key accounts, we have over 800 prescribers. And then an important leading indicator is the diagnostics front, and those results also continue to be encouraging, and its use is more than doubling in the last year and the use of blood diagnostics grows significantly each month as well. The true challenge here is the system -- health care systems' readiness and I think most critically, the capacity to detect and diagnose patients.

And so we have a number of solutions that we're working on with the health care providers to help them increase that capacity, increase the throughput for patients, a lot of educational series as well on how to quickly diagnose and treat these patients. Importantly, I think we're hearing a lot of enthusiasm about the profile of Kisunla, and that actually helps with these capacity constraints, the once-monthly infusions, the ability to stop dosing once plaque is cleared, all of those physicians have told us are going to help with some of these capacity constraints. So it's been a strong start so far.

We learned lessons from the first launch that went out there and applying that learning to what we're doing now. But it's been really positive so far in the terms of the level of support and collaboration that Lilly has been able to bring with our expertise in the field and our long relationships with these customers.

Operator

The next question will be from Umer Raffat from Evercore.

Umer Raffat

It's certainly very encouraging to see the range of new Phase III trials being initiated with Orforglipron in the past few months. But there's one trial in particular I noticed has not been initiated or may not be in the plans, which is an outcomes trial. I'm just curious what's the thought process behind that.

David Ricks

Great. Thanks, Umer, for the question. We'll go to Dan to talk about the Orfo development plan.

Daniel Skovronsky

Yes. Thanks, Umer. Of course, we're trying to cover a broad landscape of indications here that we think would be important and fit with the advantages an oral medication has in sort of primary care broad use kinds of applications being prioritized.

Outcome setting is an interesting idea. The challenges here in maintaining patients on placebo make it more and more difficult to do those kinds of studies in the U.S., but it's certainly an idea that we're exploring around the world and more thinking to come in the future.

Operator

The next question will be from Steve Scala from TD Cowen.

Steve Scala

I apologize in advance for this question. But over the past 6 to 9 months, there has been a consistent cadence of data points questioning the size of the addressable and accessible obesity market, none of which are news, but include slowing prescription trends, Lilly meeting demand at least a year early, Lilly instituting DTC and extending co-pay cards despite struggling to meet demand, Lilly launching in OUS markets despite struggling to meet U.S. demand and significant stocking fluctuations and challenges in guiding. So taken collectively, these points are concerning.

I think you will say that they all relate to the unprecedented size of the market and meeting its demand, but can you state that there has not been any conversations within Lilly questioning whether we are all significantly over our skis on this market and that the manufacturing build-out may simply be too aggressive.

Mike Czapar

Great. Well, Steve, thanks for the apology and the question. I'll go to Dave for that one.

David Ricks

Yes, Steve, I think you've been calling into our calls for most of my career. I've never had the apology upfront, so I appreciate that. I know why you're asking it.

And I think the perspective we have is that it's early days on a very, very large opportunity. There's turbulence. I'll own that.

We always seek to put projections out that we can hit with confidence, but that are also within the range of possibilities. And in the back half of that year -- last year, we fell short of that. But everything we've said is true, and we continue to believe in that this is a market with hundreds of millions of people globally that there is a unique thing here and that we can both prevent a large portion of chronic disease with obesity drugs.

And last year, we saw proof points on that from Lilly and our competitor that's not just weight loss that translates into chronic disease outcomes. You'll hear and see more of that. And people love taking these drugs.

We know that because when we run out, which we did last year, they get very angry with us. And so I have been a person who represents to the Board, the CapEx decisions, I have zero doubt that we have still more building to do and that the capacity we put in the ground so far is not sufficient to meet global demand. You'll hear more about that from us.

Of course, as highlighting on this call, we're getting close to, I think, a relief valve on that, which is the idea that you could have an oral which is scalable in a way that injectable systems just aren't really test the question legitimately what is the edge of the demand curve. But we don't think we're close to it right now. We're still gating promotion and gating launches globally.

That's a different thing, and we're building facilities as fast as we can to match up those 2 things, what we can make and what we can sell, and although we're supplying the U.S. market well right now, we'll need to do more, and I'm pretty confident in that. So hopefully, that gives you some color on the mindset here, and wouldn't overread the turbulence and prediction challenges we have. But long term, we're very bullish, and you'll see us act according to that belief.

Operator

The next question will be from Mohit Bansal from Wells Fargo.

Mohit Bansal

I have a question regarding sleep apnea. Now that you have sleep apnea on Zepbound label, how have the discussions with the prescribers as well as payers have gone so far. The one pushback we hear is that these patients are often treated by sleep specialists, and there's a general shortage of those specialists here.

So could you talk a little bit about the call points and how you're thinking about this.

David Ricks

Great. Thanks, Mohit. We'll go to Patrik for the question on sleep apnea, what the discussions are like with some of the prescribers and the initial experience so far.

Patrik Jonsson

Thank you very much, Mohit. Yes, you're correct. It's the first pharmacological treatment ever approved for obstructive sleep apnea.

So there is a lot of lifting on our side, and we will approach that as we are approaching any new disease area, partnering with advocacy organization, health care providers and massive efforts in terms of medical education. We expect this to go beyond the sleep specialists. But of course, we are starting our efforts with the sleep specialist community.

And I think that's been very well received so far. And we are meeting with them regularly conducting speaker screenings, but with the aim to move to primary care, which is a necessity because this is also a patient population that, to a large extent, remains undiagnosed. So primary care efforts are going to be required.

Operator

The next question will be from Dave Risinger from Leerink Partners.

David Risinger

So my incretin-related questions have been asked. I wanted to just pivot to the long-acting relaxin candidate VOLENRELAXIN. And so the company had advanced it into a CKD trial in the fourth quarter, but then recently canceled both the heart failure and CKD programs.

Dan, I'm hoping you could provide some more color on what drove the action plus how you now view the long-acting relaxin mechanism, including potential for future development in other cardiopulmonary diseases.

David Ricks

Great. Thanks, Dave. We'll go to Dan to talk about the VOLENRELAXIN program.

Daniel Skovronsky

Thank you. I was disappointed with the results from the Phase II trial for sure. Relaxin is an interesting mechanism, I think, sort of validated by normal human physiology during pregnancy.

But unfortunately, the results that we got in this trial didn't support proceeding with this molecule. I read that as speaking to the mechanism, but rather than the molecule. But I know others are pursuing this mechanism, and I wish some success where we didn't have it.

So we'll have to wait and see.

Operator

The next question will be from Akash Tewari from Jefferies.

Akash Tewari

So at JPMorgan, your team mentioned you expect GLP-1 pricing to be relatively stable in 2025. Are you implying that while you'll give additional discounts to the channel to improve access, that will be offset by improved adherence. Or is it more Lilly's reached a steady state on discounts at least until semaglutide gets put under IRA negotiation in 2026.

David Ricks

All right. Thanks, Akash. We'll go to Lucas to talk about GLP-1 pricing trends.

Lucas Montarce

Thanks for the question. In terms of the pricing trends that I alluded during the JPMorgan conference and getting into 2025, first, we talk about the Q4. And into 2025, what we mentioned basically is a continuation of the trends.

Remember that we had in the base period in 2023, an uncovered copay that basically created quite a lot of noise on the year-on-year comparison. So we talk about basically adjusting by that, there is still single-digit erosion on our pricing trends, and that's the same trends that I alluded that will continue into 2025. In terms of some of the dynamics on the access side, I don't know if you want to comment anything, Patrik, on your side.

Patrik Jonsson

No, I think we have really good access on the Mounjaro side, over 90% in commercial and Part D, and I've already covered the commercial space for Zepbound. We expect access to continue to improve in 2025 as well. In terms of adherence, I think we just need to reflect on the dynamics that we have experienced in this market, partly due to supply constraints, but we are encouraged with what we see on Mounjaro for patients that started in Q2 2023, we actually see a longer adherence with Mounjaro than we do with both Trulicity and Ozempic.

And as Dave referred to earlier, in terms of set bound, we expect adherence to be long here based upon the firsthand experiences that consumers have.

Operator

The next question will be from Alexandria Hammond from Wolfe Research.

Alexandria Hammond

With the Rowe partnership, how does Lilly envision this relationship evolving. And a follow-up, can you help frame the opportunity associated with Zepbound vials. And how is that expected to shift over time.

David Ricks

Great. Thanks, Alex. We'll go to Patrik to talk about Zepbound vials and Rowe.

Patrik Jonsson

Yes. We launched the self-pay system with Lilly Direct back in late August, and we are pleased with the performance so far. In terms of TRx for Zepbound, it's still low to mid-single digit.

But in terms of new therapy starts, it's actually in the low teens. So a very good start. The partnership with Rowe is not a financial or a marketing partnership at all.

It's just the opportunity for eligible patients to have the option of using the Rowe platform to purchase FDA-approved authentic medicines. And it's really about connecting that software to Lilly Direct self-pay pharmacy. And we will lean into additional partnerships along those lines with partners that really want to ensure that the patients get access to authentic and FDA-approved medicines.

Operator

The next question will be from Chris Shibutani from Goldman Sachs.

Chris Shibutani

Apologies, I was on mute. So the Orforglipron launch, you previously stated that you're doing manufacturing scale-up to be prepared for a full launch at potential approval. What is embedded in that assumption.

Can you talk a little bit about the approach for timing of Orforglipron in terms of diabetes versus obesity. Will it be simultaneous or one before the other. U.S. versus international, we certainly saw the injectable business do a prioritized U.S. launch.

And then should we also expect a similar kind of "new product" launch cadence with patient assistance programs and the implementation of channel tools like Lilly Direct, should all those be at the outset.

Mike Czapar

Thanks, Chris, for the very detailed question. We'll go to Dave to talk a bit about the Orforglipron launch prep.

David Ricks

Okay. Yes. Look, the goal here with Orforglipron because it's using different production systems that are available to us.

It's a long cycle of processing to get commercial product, but it's very predictable, and we have access to those platforms inside and outside the company. So we are building for a full launch in the normal pharma sense. And here, pointing out maybe the flip of the earlier question about demand, we have had to gate all these things to make sure we carefully match supply and demand for the injectables as is our competitor.

We do not plan for that with Orforglipron. So we will plan to launch or submit and have approvals and then launch in a full sense, including activities you're used to seeing for primary care products like sampling, co-pay, full formulary access and globalization of Orforglipron as rapidly as possible. And we're building capacities to do that.

And hopefully, that will begin in early '26. I think as Dan mentioned, the first complete package for submission in the U.S. will be obesity. But we expect diabetes to shortly follow and then these other indications that have been discussed today.

I hope that answers the question.

Operator

The next question will be from James Shin from Deutsche Bank.

James Shin

Another one for Dan on Orforglipron. I appreciate the earlier comments on indexing Orforglipron's efficacy to semaglutide and the Phase III titration schedule. But can you go over how this titration schedule may impact the Phase II weight loss, A1c and safety results published in Lancet and New England Journal.

David Ricks

Great. Thanks, Seamus, for the question. We'll go to Dan to talk more about Orforglipron.

Daniel Skovronsky

Yes. It's a good question, James, and reminiscent of the theme we had when the tirzepatide trials were going. It was a similar transition from a faster titration in Phase II to a more gradual titration in Phase III.

I think that strategy served us well in the case of tirzepatide. I'm hopeful for the same kind of outcomes in Orforglipron, which is to say that it mitigated tolerability concerns. So the GI side effects that are just known to this class seem to be significantly mitigated by slower titration.

And in longer studies and the first study to read out is not the longest study we have here. In longer studies, we were still able to obtain the sort of plateau kind of efficacy that we expect for the mechanism. So that's what we're hoping for or for better tolerability and similar efficacy as Phase II.

Operator

The next question will be from Trung Huynh from UBS.

Trung Huynh

So for the first ortho study on diabetes, thank you so much for the level set there. I have a similar question on retatrutide. We noticed in your slides, there was a Phase III readout in obesity and overweight patients with osteoarthritis of the knee as a potential event for '25.

So one of the primary endpoints is weight loss. Could that be a reasonable comp for the obesity studies in '26, unlike what you flagged with ortho and diabetes.

David Ricks

Thanks for the question, Trung. We'll go to Dan to talk about retatrutide.

Daniel Skovronsky

Yes. I'm glad you asked the question. It's a super smart question.

You're probably noticing that the osteoarthritis trial is shorter than any of the other ones. We've commented before that retatrutide is going to need longer trials. Most of ours are 80-week plus trials to reach maximal efficacy.

This is a 68-week trial. I think we also know, at least by analogy from the semaglutide trials that looked at osteoarthritis and obesity versus a more pure obesity population that even for similar length studies, there's a diminution of efficacy in terms of weight loss in the OA population for a number of reasons, including different baseline demographics, male, female, BMI, et cetera. So I think we know how to extrapolate out from the OA population to the general population, but I don't think you should take the OA population as a point estimate for what will be achieved in a broader obesity population.

We should do quite a bit better than that.

Operator

The next question will be from Kripa Devarakonda from Truist Securities.

Nicole Germino

This is Nicole on for Kripa. Can we see some bima data this year. And do you still see some benefit with a muscle preserving drug.

The recent data from Ver showed preservation of lean mass but no incremental weight loss. So with bima, do you expect incremental weight loss or weight control but better body composition. Is that what you're looking for.

David Ricks

Thanks for the question. We'll go to Dan to talk a bit about how we're thinking about the bima data.

Daniel Skovronsky

Yes. Thanks for a good question on bimagrumab. I think our thesis here has been in combination with tirzepatide that we could get incremental weight loss or perhaps a similar weight loss.

But as you point out, with preservation of what we call lean mass. I think to really show a benefit for combining the 2 drugs, we're probably going to either need to see the incremental weight loss or we're going to need to see some real functional benefits to lean mass preservation. I think just lean mass on its own, we don't really know how to understand that, and we've previously noted that we don't see any signs that lean mass changes on tirzepatide or to my knowledge, on any incretin are actually adverse in any way.

On the other hand, growing muscle could be a positive in different ways. So we're looking for new positive effects with bimagrumab. The beginning of your question, I realize it didn't come to, which is when do we see the previous Phase II study, which was completed.

We haven't been clear on exactly when we'll show that data, but this year is a safe assumption.

David Ricks

Great. Thank you, Dan. I think we have time for one last question.

Operator

The final question today will be a follow-up from Dave Risinger from Leerink Partners.

David Risinger

I was just hoping you could clarify the comment earlier. I think there was a comment about additional PBM coverage coming in March. I didn't quite catch that.

If you could just provide some more color and quantify the potential impact on the opportunity for script trends following that occurring.

Daniel Skovronsky

Let me cover that, and then I'll just close. I think Dave, that was referred to Ebglyss, which is very new in cycle, and we do expect 2 of the 3 PBMs to cover it and that gets us excited about activating consumers and raising awareness for that brand. Zepbound, Mounjaro have full PBM coverage already.

David Ricks

So great. Let's conclude it there. Thanks for dialing in, everyone, and your interest in today's earnings call and of course, in everything about Eli Lilly and Company.

If you've got follow-up questions or things we didn't cover in enough detail today in the Q&A, please follow up with the IR team. Mike Czapar leads that now. And everyone, have a great day.

Operator

Thank you. And ladies and gentlemen, this does conclude our conference for today. This conference will be made available for replay beginning at 1:00 p.

m. today running through March 13 at midnight. You may access the replay system at any time by dialing (800) 332-6854 and entering the access code 443262.

International dialers can call (973) 528-0005. Again, those numbers are (800) 332-6854 and 973-528-005 with the access code 443262. Thank you for your participation. You may now disconnect your lines.