Operator: The next question is coming from Kerry Holford from Berenberg. Kerry, your line is live.
Kerry Holford: Thank you for taking my question. It’s on Tirzepatide obesity. I’m interested to hear why you’ve taken the decision not to launch under the Zepbound brand outside the U.S. but rather seek a label expansion for weight loss to Mounjaro. Does that relate to simplicity, perhaps faster reimbursement access? And I wonder if you foresee any risk here that ex U.S. governments prefer ultimately to keep diabetes and obesity budgets separate.
Joe Fletcher: Thank you, Kerry, for the questions. I’ll hand over to Ilya to talk about the branding of Tirzepatide OUS.
Ilya Yuffa: Sure, yes. So the broader Tirzepatide outside of the U.S., it depends on a number of different factors, whether it’s regulatory or competitive market dynamics. There are some payer dynamics as well. We don’t anticipate that being a challenge in terms of negotiating reimbursement either for Type 2 diabetes or for management. We continue to have those discussions in a number of markets and are optimistic about our ability to commercialize under different brand scenarios.
Operator: The next question is from Geoff Meacham from Bank of America. Geoff, your line is live.
Geoffrey Meacham: Morning, guys. Thanks so much for the question.Dave, I know you guys formally announced Lilly Direct last fall. Should we view it as a platform to just streamline access to providers and Lilly meds? Or is there a monetization model or some market differentiation that could also play out over time?
David Ricks: For that I can start, Patrik, jump in. Yes, thanks for the question. The idea was really actually borne out of the challenges patients face every day in the U.S. and sometimes seeing doctors. And you’ll know we have a Doctor Finder tool as well as telehealth partners on the platform for migraine, diabetes, and obesity. Finding medicines and their pharmacies, that’s been a challenge. And I think particularly as supplies are tight, many patients report driving to 5, 6, seven pharmacies to find the medicine they need that simplifies that process. And then I think in addition, there’s been a lot of noise about drugs that are illicit or copies or compounded versions of Zepbound or other weight loss drugs and that’s concerning to us.
And I think it’s concerning to patients. So by going to Lilly Direct literally, they have confidence in the supply. And finally, application of our savings programs has also been a challenge at the pharmacy counter and that happens 100% of the time on Lilly Direct. We haven’t thought about it as a way to create some new retail distribution business. It’s a way to serve the patients that want our medicines better. That’s sort of the frame we’re in now. Early days. We’re trying to develop it to be smoother, better, include more products over time, have better information about physicians and telehealth providers. So look for more developments there, but good start so far. A lot of energy and enthusiasm from the patient community.
Operator: The next question is coming from David Risinger from Leerink. David, your line is live.
David Risinger: Yes, thank you and congrats on today’s updates. Congrats on today’s updates. So my question is for Dave and Dan on lean muscle loss associated with Incretin use. Could you help me understand Lilly’s take on this debate and comment on Tirzepatide data to date relative to semaglutide? What I’ve observed is that SURMOUNT-1 showed a 3:1 lean muscle loss ratio, whereas SEMA’s STEP one trial showed a 1.5:1 ratio, albeit with a slightly different assessment.
Joe Fletcher: Thanks, Dave. I’ll have Dan field that.
Daniel Skovronsky: Yes. Thanks for your question. Maybe just starting with our take on lean versus fat mass. I think the ratio of lean to fat mass is an important thing to think about. Body composition, not by weight matters to patients, for example, in risk of Type 2 diabetes or cardiovascular disease, that ratio seems to be important. The good news is that for patients on Tirzepatide, that ratio appears to improve. As you pointed out, they lose far more fat mass than lean mass. And so in every trial we’ve done, at the end of the trial, if we measure body composition, it’s better, a higher ratio of lean to fat than at the beginning of the trial. So we see this changing body composition as a benefit, potential benefit of Tirzepatide to be further explored.
Of course, it’s also a benefit we want to further extend. You’ve seen us try to improve the total amount of body weight loss. We’re also trying to improve further improve, I should say, the change in body mass composition. And that’s why you saw us acquire and experiment with drugs like [indiscernible] the number you quote from the Tirzepatide and semaglutide studies seem right to me. Of course, they’re not head-to-head studies. But it does raise a question here about whether there’s a potential benefit of GIP-1 — GIP agonism here in addition to GLP-1 agonism. That’s probably the way I would interpret this data.
Operator: The next question is coming from Evan Seigerman from BMO Capital Markets. Evan, your line is live.
Evan Seigerman: I would love to get your take on how you’re thinking about the opportunity for the oral GLP-1s. We’ve seen some mixed data from competitors. And I just would love to get how you see this evolving in context of your investment in orforglipron.
Joe Fletcher: Thanks, Evan, for the question. Patrik, maybe you talk about how we think about an oral agent.
Patrik Jonsson: Thank you very much. When we look at the opportunity in obesity, we have more than 110 million in the U.S. and 650 million globally. I think taking into account the current supply constraints across markets, it’s impossible to reach all of those with injectables. So I think that’s the big opportunity we have for orforglipron. And what we have seen so far in Phase II, if we can replicate those data in Phase III, we have an oral medicine here with a weight loss along the lines of the best competitive Incretin, not at the level of Tirzepatide, but that’s the level of the best Incretin in the marketplace and with no food or water restrictions. So we really see the opportunity here with orforglipron to reach patients across the globe.
And there is another component as well. If we look at the current market, approximately 20% of patients with obesity are actually concerned to take an injectable. So that’s another opportunity with orforglipron. So we believe that’s a really strong drug in our hands moving forward in the space of chronic weight management.
Operator: Next question is from Steve Scala from Cowen. Steve, your line is live.
Stephen Scala: There could be several reasons why Lilly is not initiating a Phase III trial of Tirzepatide in NASH. First, Lilly believes it has better molecules. Second, there is something in the Phase II data which is less than ideal. Or third, Lilly will do a Phase III. It just hasn’t gotten around to finalizing plans, but that really can’t be yet. To draw a parallel, you’re starting a Phase III with LPA without even telling us the Phase II was positive. So what would be best for us to conclude about Tirzepatide and NASH?
Daniel Skovronsky: Yes. Thanks, Steve, for the clever analysis here. So first of all, I should just say, we literally just got this Phase II data so give us a chance to determine our next steps on the plans, probably debug at least one of the hypotheses here. There’s nothing bad in the data that would stop us from going to Phase III. In terms of having a better molecule, probably we do in — of course, we don’t have that kind of Phase II data here for retatrutide. And so that’s based on liver fat reduction, which was just incredible in the Phase II trial. Still though, I think having a positive Phase II trial here with really a meaningful data and NASH obligates us to think about next steps. As I said, that’s going to the FDA to talk to them.
I would say in terms of planning a Phase III for any drug in NASH, a really important priority for us is to move away as much as we can from liver biopsies and replace them with non-invasive testing. I think we and others in the field have made a lot of progress there. We see analogies here to other disease areas. And we hope that in the future, it will be possible to conduct Phase III NASH trials without relying on biopsies. That would really have a profound effect on the feasibility of running these trials quickly but also in the clinical application of NASH drugs, where those non-invasive biomarkers could be identified patients for treatment and monitor response to therapy rather than biopsies.
Operator: The next question is from Chris Shibutani from Goldman Sachs. Chris, your line is live.
Chris Shibutani: Duration of use of the GLP-1s across the diabetes and obesity populations. Previously, you’ve characterized the duration in the range of 15 months for diabetes and have commented that you don’t believe we have enough experience. Any updates there? And when do you think we will have enough experience to be able to get a better gauge of duration of use median in the obesity population, at least initially?
Joe Fletcher: Thanks, Chris. Patrik, do you want to comment on duration of therapy?
