All right. Thanks everyone for team from Cytokinetics, represented by Isaac, who's their Chief Business Officer, Andrew, their Chief Commercial Officer, Dan, who's VP of Clinical Research and Executive Medical Director, and Sung Lee, their CFO. Thanks for being here.
Thanks for having us.
A lot of exciting developments for the company over the past few months. You know, maybe we can start on the commercial side, actually. You know, one of the key investor debates heading in had been the REMS, and sort of what the real-world label would look like. Maybe we can almost start there. Now that you have the label in hand, now that you're commercializing the drug, how do you feel about what was in the REMS, what was on the label, and how that's maybe enabling the success of MYKORZO?
Yeah, I can certainly start. The label and the REMS were as we expected. They were, especially the REMS was very positive in terms of the echo monitoring window of two-to-eight weeks, a lack of DDI monitoring as part of the REMS program, a broad indication statement for symptomatic HCM without mention of New York Heart Class. We were very positive on the REMS and the label that support the differentiation. That differentiation, we do pulse surveys in the market since we've launched, we've done two. The differentiation that I just described from a label is reading out one in practice and two in pulse surveys and what physicians are stating, which is from a clinical differentiation, the rapid and onset symptom improvement, reduction of gradient, and the safety and efficacy.
You know, these things that resonate very well with physicians and practical aspects of a REMS program that has a two-to-eight-week monitoring window for echo as well as lack of DDI. That two-to-eight-week monitoring window, you know, one thing we wondered was would physicians just follow a four-week monitoring window, which is what they're used to. In the data, when we look at it from our dispensing pharmacy, we see a range of that two- to-eight weeks where physicians are leveraging that echo window, so you can get a refill on the same dose or if you want, the physician and patient can titrate as quickly as two weeks. These areas of differentiation point, we see that in the pulse surveys, and they point out in terms of clinical practice.
Got it. I guess to build on that, I guess, how are you thinking about where patient starts are going to come from? Is it competitive switches? Is it new starts that you're building? I guess, you know, we've talked a lot about what matters to physicians, but you know, what matters to patients here about, you know, MYKORZO.
From a start point of view, there's over 100,000 symptomatic, obstructive HCM patients in the market, probably around 120, meaning eligible for treatment. We feel there's over 80% of the market still available. Naive, that's where our data is and our focus. Our focus is on new patients. I don't think a physician, a patient, or us would advocate for switching a stable patient. The switch data we've seen in the first quarter, over 95% of our patients are naive to treatment. We do see some switch, but it's less than 5%. In terms of the patient type, we've had, you know, about 15%-20% of our prescribers have been naive to CMI, never written a CMI before.
We've had maybe another 20% who are low CMIs and a little over 50% who are in the majority of the 80% of the market. We're seeing prescribing across physician segments. That differentiation I described is consistent across physician segments. You know, we're seeing growth rates. We know the nine weeks we had in Q1, in the earnings call, we purposely put in number of physicians who prescribed at least one prescription as well as the number of patients just to show a trend in growth. We were seeing month-over-month growth, including from March to April.
Got it. I think there's always gonna be people who wanna draw comparisons to the other approved CMI in terms of how the launch is going. You know, maybe on one hand, big picture, is that a fair way to compare the launch of MYKORZO as a base case? Then sort of you've touched on these before, but you know, what are you hearing from feedback, you know, in terms of physicians who are maybe making the choice of, do I wanna put a patient on MYKORZO? Do I wanna put them on a different drug, and why they're ultimately going with MYKORZO?
Sure. I mean, our launch aspiration was to be at or better than where, you know, the BMS CMI was in their first year of launch. I think we're tracking very well to be above what that was for BMS. We're very pleased. I think across all launch metrics that we looked at, they surpassed our expectations in Q1. You know, percent of reimbursed that are paid, time to reimbursement, new to brand share, total prescriptions, et cetera. We're very pleased at seeing that overall. In terms of feedback, the feedback we've received from physicians is very positive. Overall, you know, I mentioned those pulse surveys. There's a high intention to prescribe, there's a high level of awareness, and physicians who have seen our label.
We have physicians attending speaker programs, physicians that are trying in clinical practice and repeating. It's early days, but we're very positive, many of the signs we're seeing.
Has there been any friction with onboarding REMS or, you know, pairs of physicians of signing up for it, just getting that operationalized? I think one of the concerns heading into the launch was, you know, would maybe smaller centers wanna handle two different REMS. Are you seeing any of that in the real world?
The REMS itself, as I mentioned, kind of the practical differences, we get a lot of positive feedback of each echo you can increase dose, no DDI as we talked as part of REMS. The systematizing of REMS actually going into a REMS system, we rolled out that in phases. That has been a friction point for some offices, where initially support staff didn't have full access to REMS. They do now. We did an enhancement in the end of March, early April. We're getting closer to where we want in terms of REMS full system functionality, but for some that was a point of friction early on launch.
Got it. I know it's early, but are patients in general, are you seeing them titrate up to the full dose? Are you seeing them stay on drug in terms of compliance, persistence?
Yeah. As you say, it's early. Most of our dosing is 5 milligrams. We do have patients on 15 mg and 20 mg. That's a minority just 'cause of, you know, they have that flexibility in terms of how long that takes. When we looked at persistency and compliance, as a category for us for our own internal modeling, we looked at analogs, we looked at PAH, we looked at TEER, heart failure, the other CMI. CMI in general was the highest of all those categories at the end of the year. Our expectation is by the end of year one or one year of therapy, that somewhere in the range of 70%-80% of patients would still be on therapy who had started therapy. We'll certainly report that when we have the data.
We don't really have many drop-offs at all right now, again, because it's so early.
You've talked about wanting to be at parity on payer access with the other approved CMIs by the end of the year. Can you just update us maybe where you are now across both the public side and the commercial side?
Sure. Sure. The mix of payers, the market is 60% Medicare, around 30% commercial, rough number. Medicare, from a comparability point of view, our expectation is in the second quarter, the quarter we're in, we'll be at parity with BMS and Medicare access. Right now we're close to 90% parity. Commercial, the 30% of the market we expect to be at parity in the fourth quarter. You know, we're approaching 50% of commercial lives covered in commercial. There's the major PBMs. There's a, you know, three major PBMs that we're in conversations with. You know, again, our expectation is that we would have that coverage. We don't want preferential coverage. We're really looking for a comparable access and the ability to compete on clinical profile.
Got it. Before we turn to Katia, some of the work there, maybe two final questions on commercial. As you're also expanding on an international opportunity, potentially a launch in Germany, I guess any unique considerations that we should be thinking about in the European Union and elsewhere?
Europe, we're approved in the European Union. We filed in Swissmedic, we filed with MHRA in the U.K. Europe, the next hurdle is getting reimbursement. The government is the payer. The countries launch based on reimbursement. Germany is the first to launch. Germany is about 30%-33% of Europe overall in terms of opportunity from a revenue point of view. We have our full German team. They're in the market. We're in the launch process right now for Germany. Probably the next to go towards the fourth quarter would be U.K., Netherlands. Obviously, Netherlands is not in the Big five. Big five markets, I talked about Germany. The other ones, we've submitted all the dossiers now for reimbursement, we'll wait.
We're probably in the window of nine-to-15 months, depending on what the jurisdiction is for Europe overall. It's really the payer dynamic in terms of the government and going through that health technology assessment process with the expectation that the price in Europe is around 15% of our current price in the U.S.
That's really the big difference.
I guess on that point, you know, there's been a lot of companies that have even paused European launches because of Most-Favored-Nation concerns. You guys forging ahead. I guess how'd you come to that decision?
I mean, when we've looked at MFN, really the GUARD Model element of MFN, which is in draft right now, is the element that would impact us if it, if it gets implemented as is, I guess been discussed in the kind of public domain. I don't think we or any of the consultants we talk to think it's going to be in that. There may be an orphan designation carve-out. There may be the ability to negotiate like the Big Pharmas did with the government in some way. If it does go through, then there's a reference basket of countries, and it's 25% of those countries where you're matching, depending on ultimately how they do that matching, that would be a single-digit impact to us in terms of gross to net.
We're moving forward with Europe. We've licensed you know, Japan, which is part of that market basket. Even if we didn't launch in Europe, we still have, you know, Bayer in Japan that could trigger MFN. We'll go through the mechanisms, we'll keep track of where MFN is going, but we thought it was important for, especially for patients, to launch in Europe and other parts of the world.
There's been a lot of focus on ACACIA-HCM, but you guys also have the MAPLE-HCM sNDA is a near-term regulatory event, which, you know, has the opportunity to further grow the commercial opportunity for MYKORZO. I guess what's your latest thinking on maybe the expansion that that can add?
The MAPLE-HCM doesn't include a new population, like ACACIA-HCM is a brand-new population.
Yeah.
MAPLE-HCM just really describes the possibility of using monotherapy in terms of MYKORZO. I think the key element for MAPLE-HCM when we've done research, it really expands penetration in oHCM, so more patients get treated, and it expands preference share as well. That's what our research says. We'll see how that plays out. What MAPLE-HCM does from a research point of view, when you look at the general cardiologist, not the KOLs per se or the centers of excellence, it's a call to action because a standard of care beta blockers doesn't doesn't have an efficacy component relative to obstruction. There's biomarkers that it doesn't impact with a major one like NT-proBNP.
If that ultimately gets added to guidelines, which is a big element for general cardiology, as well as the element or, I'm sorry, the agent, a beta blocker that is in wide use today not having that impact, in combination with the REMS program I described, I think that's where we really see MAPLE-HCM helping expand the market in terms of breadth of prescribers.
Got it. On ACACIA-HCM, I think you've been two weeks since the data-ish, something like that. Trial met both of its endpoints. I guess, how do you think about the efficacy that we saw there, how meaningful it might be to physicians?
Yeah, I guess I'll take that. We've got some preliminary feedback just from our academic steering committee, from KOLs, heart failure space, and others around the world that we met with in Barcelona at the HFA meeting last week. Just to give a general scope of that, there's a tremendous enthusiasm for the results overall, words like home run, transformative are what people are using to describe it. I think the reason that's happening is because you just don't see that you can't find heart failure study that demonstrates benefit in both symptoms and exercise capacity in this way, and then supported by secondary endpoints, and particularly looking at nHCM in a disease state where there's no other treatment available to it. It's a really high unmet need, and the robustness of the overall totality of the data is very significant.
As you will have observed, no doubt, the KCCQ has some lumpiness in the placebo effect, which maps out at week 36 as a slightly lower difference between aficamten and placebo. When you look at the overall totality of the treatment effect, you're really in the 5- to- 5+ range of difference. With regard to peak VO2, there are some ways to index that if you're interested in it. Ways to think about it include looking at HF-ACTION, which is one of the largest and best documented studies showing improvement in exercise capacity in a heart failure population, which shows a difference of around 0.5, 0.6 is incredibly meaningful. If you look at Ahmad Masri's recent publication in oHCM indexing minimal important difference in the oHCM populations in MAPLE-HCM and SEQUOIA-HCM, again, you see 0.5 or so.
It's a significant, important clinical difference. When you look at that 1.0 number, which is the number that we have been always thinking about, which is a convenient number, it really stems in HCM from this 2016 paper from Caroline Coats and Co. Great paper, which shows that a difference in peak VO2 of one is associated with death transplant difference. It stands to intuitive reason that a lesser number would be important for symptoms before you achieve hospitalization or death or transplant. There's a general overall sense that that peak VO2 difference of 0.67 and the KCCQ difference over the totality of the study in combination demonstrates a really important benefit for patients, supplemented by improvement in NYHA, improvement in NT-pro, improvement in maximal and submaximal exercise capacity. Obviously, we haven't released the full results.
We'll look forward to exploring that more completely, but there are also secondary and exploratory endpoints that further support the overall clinical benefit of the treatment.
I guess on the other side of the placebo lumpiness was the fact that the effect seemed to deepen over time. I guess to what degree do you think that's real? Do you think you've actually seen the full efficacy of the drug? If patients stay on therapy in the real world for longer, could it be more? I mean, do you have data from any of your open label studies to suggest that might be the case?
Yeah, great question. I mean, our hypothesis going into this, and it's really been the hypothesis of the overall field, is that in the absence of a hemodynamic lesion that can be acutely remedied, such as LVOT obstruction, that there is some time required to achieve some type of remodeling and gradual improvement over time that would lead to clinical benefit. Hence, the studies in nHCM are designed to be longer exposure. I mean, that was the hypothesis going in, and I think that's kind of bearing out. Whether it's required or whether that maps onto actual structural changes that can be measured and indexed to those clinical improvements, I think is something that we're going to be exploring as we come out with more data.
You'll know everybody will be familiar with our track record from SEQUOIA-HCM and Maple of coming forward not just with primary results, but trying to supply the community with robust analyses of secondary and exploratory endpoints to provide a full complement of data to help understand the clinical benefit.
I think you're pointing to a really important point with the long-term extension data, and we have seen in our long-term extension, if you look at the 96-week paper, you see this persistence of benefit in that small 34 patient cohort from REDWOOD-HCM Cohort 4 that continued for 96 weeks, and we are following all these ACACIA patients into FOREST-HCM. We will continue to have longer term data on that. We will be exploring also the MRI sub-study for ACACIA, which enrolled a relatively large number of patients and which will give us additional data on remodeling. I think we'll be able to answer some of those questions really well in the near term.
Got it. One of the things we had heard from, you know, some physicians heading into ACACIA was that nHCM is pretty heterogeneous. There might be different patient populations that respond differently. Now that you guys have the data in hand and it's clearly positive, I guess, how are you thinking about maybe the urgency that physicians would have to treat patients? You know, is this something that's going to be used uniformly and broadly across the patient population? Are there groups that physicians might think might be better suited for the mechanism, less well suited?
I mean, this is, you know, an incredibly important clinical question. You know, I think in a way it would be hard to answer it without going through the full scope. Hopefully, we'll be able to have a chance at some future date to discuss the full scope of the data that we have available and looking at heterogeneity or lack of heterogeneity thereof. We obviously have pre-specified all that in our primary analysis. I would say that in general, though, these results and the overall enrollment criteria reflect an impact on the overall nHCM population as is seen in HCM clinics around the world.
Although it is a heterogeneous disease, the fundamental mechanism of it, that hypercontractility with elevated LVEF and worsened diastolic function, if you select a patient who actually has HCM and give them aficamten, as was done in ACACIA, in general, overall, you would predict that you would tend to see a benefit. Mapping that into the clinical environment, I think what we see when people apply new therapies is that what happens is, particularly in this area where there is no existing therapy, and you have a medication that you're familiar with, and you know the safety profile relatively well, and it's relatively predictable.
What you have is an opportunity to try patients who have that diagnosis and to see how they feel, and in those cases where they achieve benefit, to continue therapy, and if there are cases where they don't achieve benefit, to alternate, to change or discontinue therapy as the case may be. My last comment on this would be, as I said before, we will seek to provide as much as we can transparency as we get to these results, full-on results, when we can present them around any heterogeneity or anything that was observed, that people can have a full idea of how this might map out across the nHCM population. I don't think there'll be any surprises as we move in that direction.
Got it. Maybe bring it back to commercial again. I mean, you've talked about the size of the nHCM population, that it's growing, diagnosis rates are increasing. I guess, what's the latest on the epidemiology there? I mean, how confident are you that it's going to be maybe about equal over time to oHCM, and should we be thinking that there's going to be an equal contribution from oHCM and nHCM to the MYKORZO opportunity?
I mean, there was a claims analysis, I think it was six or seven years longitudinal data that looked at O versus N split. It's within the last six months, the conclusion was there's a little over 400,000 diagnosed HCM patients. The split is 50/50. Pretty close to 50/50. There might be more in the O, those that are symptomatic on the O side is probably around 60%. Those that are symptomatic on the N side is probably in the 45%-50% range. That translates to, you know, conservatively around 120,000 oHCM patients that are symptomatic and eligible for treatment, and probably around 110,000 nHCM patients that are symptomatic and eligible for treatment.
You consider, I'm assuming that MYKORZO would be first to market, have a several year head start, and that ACACIA will be supportive of that, and that MYKORZO and oHCM are, you know, this year we said we would have greater than a 50% NBRX share, our expectation which we'd be market leaders there as well. nHCM may have a greater contribution just given the competition set, but, you know, both are gonna be meaningful.
Got it. You guys also have a whole pipeline, so I wanna spend the last maybe two minutes touching on some of that. You know, CK-586, it has a name, but I'm gonna mess it up, so I'm just gonna say CK-586. Continues to enroll. You guys are expanding that study. I guess, how do we think about what data we may get, you know, over the near term? Given the some overlap in mechanism, I guess, are there any learnings to take away from the nHCM studies that may apply to, you know, this other program?
Yeah. CK-586, which we call ulacamten.
Haven't had time to practice yet.
We're looking to complete enrollment in cohort, the first cohort by the end of the year. The important question that you asked about takeaways, really important. Just, you know, I can draw the same conclusion you would, which is that the results of ACACIA inform positively on the hypothesis that if you modulate hypercontractility and the patients experience heart failure due to diastolic dysfunction, that you can see important changes, symptoms, and important clinical findings such as NT-proBNP, exercise capacity, and so on. We would expect that that would support the hypothesis for HFpEF as well.
Got it. We've got 15 seconds, so I'm just gonna ask anyway. omecamtiv continues to enroll. Can you talk about the progress there?
Good progress. Looking to complete enrollment in the coming year. Looking for results in 2028 or 2029.
All right. Perfect. Right on time. Thank you guys so much for being here. It was really informative.
Thanks.
Thanks a lot.