Amgen Inc. (AMGN) Earnings Call Transcript & Summary

Okay. Got it. Okay. Now I want to go over to olpasiran. And again, Thomas addressed some of this in his opening remarks. So I think I know the answer to some of these, but I figured I'd ask them anyway. So obviously, we need to see more data from Novartis. But before we see that, just remind us of kind of the key differences in terms of your asset, but also the trial design and then what you'll be looking for in the Novartis data to either give you more confidence or less confidence in those features of your drug and your trial to -- that we should all look to when we see the data, assuming that AHA in November.

Olpasiran is a small interfering RNA that targets Lp(a), which is a genetically defined cardiovascular risk factor and that risk cardiovascular disease increases with increased Lp(a) in populations, 1 in 5 of us here today has Lp(a). So get yours checked. It's now part of the lipid guidelines to do so and know your risk to modify your risk around Lp(a) for sure. These are facts that aren't influenced by the Novartis readout of late. Olpasiran is a very powerful medicine. It has about a 95% reduction of Lp(a), 95% to 99% compared to pelacarsen, which was more like 70% to 8% in various clinical studies. This medicine is also given quarterly, which is a potential advantage of the medicine. Our clinical trials are a little bit different. We targeted a higher index [indiscernible] measure, 200 animals versus 150 on that study. And we chose a different endpoint rather than a 4-point [indiscernible] endpoint that includes stroke. We focus on a 3-point base endpoint as our epidemiology analysis did not see stroke as a strong driver of outcomes mapping to Lp(a). With that said, the Novartis data caught our attention. We had going into their data readout, a predefined set of actions. And we're now just waiting to see what the data actually are. All that's been communicated to date is missing the primary endpoint of the overall study population. That can mean a lot of things. And so we'll go into AHA, where we presume also these data will be presented. And like many in the community will be interested to a several parameters. It's a long list, by the way, and so I don't want to consume the rest of our time together, but these large cardiovascular outcome trials afford a possibility to really go deep into a statistical hierarchy, if you hit the primary, which they [indiscernible] did not. So we're going to take directional descriptive guidance from things like response to the medicine, a greater response to the endpoint based on the index Lp(a), the admixture of LDL-C control, which has been improving things to [indiscernible] work in Repatha in the broader community as well as predefined subsets of patient populations. A lot of people are interested in ASOs versus siRNAs as a general theme, and we are as well, intending to be a real contributor to this pharmacology. I'm interested to know how that medicine was tolerated as an ASO with respect to local active site injections, systemic responses and maybe also how they navigate COVID, which was tricky for cardiovascular outcome trials. So there's just a lot to learn from that study, and we just haven't learned it yet.

You mentioned one of the things that was a question, I think, going into the trial is just background treatment. Obviously, that has improved significantly, thanks to Repatha, also GLP-1s, is that an area that you think could have influenced it? And are there any differences in terms of your population versus their population, high level that you think could also be another factor we need to think about?

I won't speak too much to the differences in populations. There's a lot we've not shared for competitive reasons about the parameters of the patients that we've enrolled on this study. But I do hope that the reason -- one of the driving reasons that the event rates are a little bit lower is improving background care. I will say that our real-world evidence would suggest that we still have a very long way to go even with the tools that we have, like PCSK9 inhibitors like evolocumab or Repatha in order to really read drug efficacy through to broad population drug effectiveness. But LDL-C will be an interesting and important parameter to look at as these 2 biologies, both inflammatory lipoparticles, are converging on the same endothelial and vascular smooth muscle pathways of inflammation and atherogenesis.

Okay. Maybe just one for [indiscernible] just on the treatment -- importance of treatment guidelines in cardiovascular disease. So again, let's say, olpasiran has positive data 2028. What does it mean from a guideline perspective? Like what's going to be different guidelines to really kind of move the needle? Jay mentioned increasing testing on Lp(a), but how important are guidelines? What have you guys learned from kind of the Repatha situation?

Yes. So I think when it comes to guidelines, especially in cardiology, they're obviously quite important. I'd say specifically more recently for Repatha, not only where the guidelines important from an update even though they did not yet include Vesalius but the adoption by the primary care community of those same guidelines, I think it's been a major driver of better LDL-C control, more recently overall. In terms of the guidelines for Lp(a), look, it's really hard to predict the time line of guideline updates in cardiovascular disease. I think it was 7 or 8 years between guideline updates this last time. We were excited to see that LPLA testing was on these guidelines, obviously, pending readout of trial. But after the fact it may be several years before guidelines are updated. I will say there is a different behavior when a patient gets a high Lp(a) than a high LDL-C with that high Lp(a), given how infrequently it's tested and just seeing that it's a genetic disease, we do see patients much more open to really managing cholesterol in a major way. And so we do see an activation pathway through its normal going into the LDL pathway that's different than with a high LDLC where we see patients obviously often try to diet, exercise and take mineral statins in order to get their the down. So different patient population may ultimately yield something. Again, we have to wait and see what we see from the pelacarsen data to understand what it could mean going forward, though.

Okay. Got it. Maybe just going over to another cardiometabolic pipeline asset, which again is I think an increasingly be front and center here as we go to '27 [indiscernible]. Maybe, Jay, you could just remind us kind of the target profile here that you're aiming for with these large Phase III trials that you're rolling out. And it sounds like enrollment has been going pretty good.

Enrollment to the Maritime Phase III program has been outstanding. We recently completed enrollment end of August. I [indiscernible] of our obstructive sleep apnea studies. And this is a sweeping set of in the fullness of time a dozen Phase III [indiscernible] trials that will establish MariTide, we believe, as an important medicine for the treatment of obesity and its most comorbid conditions. And then studying these diseases in one parallel approach, we are starting to get a shape of the rising target product profile. And in a field that has had a lot of innovation and a lot of, I would say, redundant innovation around weekly injectables, MariTide starts to emerge as a bit of a singularity, a medicine that because of its monoclonal antibody background is by design built to be monthly or less frequently dosed. This is very important when we think about persistence. There's now more Americans who've taken a GLP-1 and no longer take it that are on it right now. Why is that? Why do half of patients stop this medicine, these helpful weekly medicines at a calendar year. And we've been working to really understand this out in the community and [indiscernible] and others, [indiscernible] have led this effort. And a lot of it comes down to challenges associated with weekly injectables, symptoms associated with the weak injectable access and durable access to the medicine. Because of the monoclonal antibody backbone, we expect MariTide to be an optimal medicine to start on if it's your first GLP-1-based medicine and then stay on for the long haul as well as to switch from a weekly injectable or an oral that can also not be very well tolerated or as efficacious to switch and then stay on MariTide. And the Phase III program will create these data. We've reported the activity of MariTide on an every 8-week administration basis. And we've also shared the insight that on every 12-week basis, maritime with more of a maintenance mindset is also quite active. When you couple this with outstanding tolerability at target dosing, the target private profile of MariTide starts to be really unique. Now you might know that the GLP-1 injectables grew up as twice-a-day medicines and then chemistry achieved once-a-day medicines and miracles of chemistry achieved ultra long-acting weekly lessens. And this medicine, owing to its flexibility and dosing schedule will be very appealing to patients. Very appealing to providers and potentially the payers as well. So it's our work now to focus on the execution of the broad Phase III program and turn in outstanding data, which won't be this calendar year on the Phase III program, but we'll have more to say about that in the new year.

And just remind us on the -- I know you guys have done a lot of work on the titration steps to kind of minimize the GI tolerability that you see with the GLP-1 axis. So where are we on that journey now? And do you ultimately think you'll end up in a place that the rates look very similar to what you see with Zepbound for example?

Yes. Thank you. It turns out for MariTide, just like all the GLP-1 medicines, whether they're injectable or oral that the index dosing, the initiation of therapy benefits from dose escalation over a period of time. And through a series of Phase I and Phase II clinical trials, we prepared the data necessary to establish the right dose and schedule for -- with -- for MariTide, a 3-step dose escalation to target dosing that takes 2 months to complete from 21 to 35 to 70 milligrams. Curiously, once a patient has had 70 milligrams, they are attenuated to the GI or other side effects of MariTide largely such that you can go right to target dosing even if it's 350 milligrams, owing to a need for a substantial weight loss. And then that turns out to be quite unique. So we will see in our Phase III program if these Phase I learnings read through to competitive tolerability, which we expect. Importantly, at target dose, we think MariTide can be quite differentiating. We more and more hear about day of injection, nausea and vomiting and challenges associated with the weekly injectables and the oral even. And here, MariTide owing to its very smooth pharmacokinetics that the antibody just kind of hangs out in the bloodstream, not hitting the area postrema with GLP-1 agonism with every excursion from trough to peak in Cmax, target dosing with MariTide is remarkably well tolerated. So we'll have more to say on that when we see the Phase III data, but we expect a competitive profile.

Great. And maybe just last one, is the Pfizer is working on a monthly program as well. Again, maybe just talk to us about anything that struck you at ADA about their profile versus what you see for MariTide in differentiation as I think a lot of investors are doing these cross-trial comparison side-by-side like who's going to have more share in the monthly market, the time lines are pretty similar. So as you look across that long-acting program, what are some of the key features that you give MariTide to leg up?

Well, Pfizer and others are performing a lot of the standard. I'm a discovery chemist, performing a lot of the standard [indiscernible] to make one of our really short-lived biomolecules longer lived, adding a lipid can lead to association with albumin, stays around the bloodstream just a little bit longer, various formulations and gel formulations, of course, have used in the past. And these may lead to tolerability over 1 month, but I do believe that it will be hard for the measure up as an efficacy endpoint. We'll see as the data reads out, and it's always hard witcross-trial comparisons. But I know that some of these companies, including Pfizer, are studying those very medicines with weekly dosing. We have no weekly study of MariTide. In fact, we're moving more towards every 8 and every 12-week dosing through our ongoing maintenance and switching studies. So I do believe that there's just nothing like maritime from a durable efficacy and durability of effect today in late-stage clinical development.

Maybe [indiscernible], I would just go to you. Just high-level this market has been front and center, I think, for the last several years in the biopharma sector, and I think estimates to $190 billion. Just what's the company's kind of high-level go-to-market strategy. We've seen the rise of the DTC channel here. You guys have leveraged your own DTC offerings for some of your other products. So maybe just talk to us about how you guys lean into that. And then Thomas, you mentioned you had some consumer background as well. So maybe there's something you want to add as well to that conversation.

Yes. So thanks, Terence. I think last year, we announced our Amgen now [indiscernible] our first direct-to-consumer program. We now have, I believe, 4 or 5 medicines within it. It has served 20,000 patients over the last year, 18,000 of those or Repatha patients providing us early learnings of how to operate within that channel. Look, it's a huge category. I think there's almost 1 billion people on the planet that could benefit from these medicines. There are offerings, good offerings today that are starting to penetrate that. Over time, we see that market fragmenting into separate submarket. We think MariTide can play both in the induction phase. And importantly, in the maintenance phase, where we know, as I said earlier, more patients have started and stopped these medicines that are on them today. We look forward to bringing kind of some of the capabilities that we've built around Repatha and [indiscernible] very large markets where we're treating lots of patients to bring MariTide forward, building on those capabilities and going more into the traditional ACP setting, but also into the direct-to-consumer setting once we get there. A lot of this will depend on the profile we see, and we'll see the totality of that profile will help us define where we play in which markets going forward. But Thomas has a really good perspective here from his Galderma days, specifically on the consumer side. Do you want to add, Thomas?

Yes. As you said, it really depends on the profile. And I think Jay has characterized it really well, what we're expecting there. When you then translate that to the more consumeristic side of the market, there is a real shift happening where patients no longer act as patients but as active consumers and make a choice and maybe in this case, we're an ordering, et cetera, they want to know about what their health status is and involve themselves in the choices. So that starts with how they consume data, how they use AI that they go to social media in the previous place. We knew exactly before any treatment decisions. We have 5 visits to social media website. So therefore, it's important that you're not only showing up branded, but also you drive unbranded awareness to satisfy people's information collection requirements. And then the path to treatment is also a different one, and you have to make it as smooth and simple as possible. And then these patients go and choose the treatment outlet, maybe [indiscernible] or whatever or even centers on that basis. And then the final point is these patients are commitment patients. they make choices about their life, be it on the aesthetic side, but also about their health levels that they want to have for themselves and commit to that and stay on that for longer term and are happy to pay cash with it. So you have to really treat them in that way, but what you get in return is a lot of stickiness from them. Really exciting area and it couldn't be at a better place than Amgen at this point in time.

Great. Well, I think we're up against time. But thank you all so much. Really appreciate it.

Thank you.

Thank you.