Greetings. Welcome to the Mineralys t op-line data conference call, Launch- HTN and Advance- HTN pivotal trials. At this time, all participants are in listen-only mode. A question-and-answer session will follow the formal presentation. If anyone today should require operator assistance, please press star zero from your telephone keypad. As a reminder, today's conference is being recorded. It is now my pleasure to introduce Jon Congleton, Chief Executive Officer of Mineralys. Thank you. You may now begin.
Thank you, Operator. Good morning, everybody. Before I get to my prepared remarks, I just want to say I'm thrilled with the news that we shared with you today. We had high confidence in the studies and the designs that we put together, and frankly, the near-flawless execution of our team. Certainly, what we believe is the transformative nature of lorundrostat. To finally see the results, I just—I can tell you the team's excited. I'm thrilled with the results that we've seen. We're going to go through a great deal of data today, but just fundamentally, we're thrilled to be at the stage we are from where we were with Target-HTN to now two pivotal studies reading out so robustly as we've done.
I just wanted to let you know the team is thrilled to be able to bring this news to you today, and we'll be walking through a great deal of the details within the slides that we have. The remarks made during this conference call and webcast will contain forward-looking statements regarding our financial outlook, regulatory, product development, and commercialization plans, as well as research activities. The statements are subject to risks and uncertainties that could cause actual results to materially differ from those forecasted. A description of these risks can be found in our most recent 10-K on file with the SEC. Okay. Joining me today on the call are Dr. David Rodman, our CMO, and Adam Levy, our CFO.
As I said, I'm very pleased to speak with you this morning to discuss the positive top-line data for both of our hypertension pivotal trials, Launch-HTN and Advance-HTN. We have now executed and successfully completed three positive trials of lorundrostat in uncontrolled and resistant hypertension patients, with all three trials demonstrating a meaningful and consistent efficacy, safety, and tolerability profile of this novel, highly selective aldosterone synthase inhibitor. This is a significant outcome for the 15 million-20 million uncontrolled hypertension patients in the United States alone that we believe could benefit from a targeted aldosterone-directed treatment. The Launch-HTN trial is the largest aldosterone synthase inhibitor trial to ever read out. This global trial enrolled 1,083 subjects who had failed to achieve their blood pressure goal while compliant on their existing regimen.
In this real-world trial, the 50-milligram, once-daily lorundrostat arm demonstrated an absolute reduction of 16.9 millimeters of mercury and a 9.1 millimeter mercury placebo-adjusted reduction in their systolic blood pressure at week six. The benefit was sustained with potential further reduction through week 12, with a 19-millimeter mercury absolute reduction and an 11.7-millimeter mercury placebo-adjusted reduction. Reductions in blood pressure of this magnitude have been linked to significant reduction in overall cardiovascular risk. Lorundrostat continued to demonstrate a modest impact on potassium and a safe and well-tolerated profile. Advance-HTN is our highly rigorous pivotal trial evaluating lorundrostat in confirmed, uncontrolled, or resistant hypertension patients despite an optimized background treatment. This study was conducted in partnership with a team at the Cleveland Clinic.
The results from Advance-HTN and the 50-milligram, once-daily lorundrostat arm were highly statistically significant on the primary endpoint with a 7.9-millimeter mercury placebo-adjusted reduction in systolic blood pressure, as measured by the gold standard 24-hour ambulatory blood pressure monitoring at week 12. The safety and tolerability of lorundrostat was consistent with what was demonstrated in our Target-HTN proof of concept trial and in Launch-HTN. We're also excited to share that Advance-HTN has been accepted for a late-breaking presentation at the ACC 2025 on March 29th. Due to the embargo restrictions, we will be limiting the information that we share today on this trial beyond the top-line efficacy and safety data.
Based on currently available and in-development treatment options for hypertension, we believe the results of both of these pivotal trials may position lorundrostat as a transformative option for patients with uncontrolled and resistant hypertension. Since our inception, it's been our mission to bring what we believe to be the best-in-class aldosterone synthase inhibitor to the market, with the potential of helping the millions of patients dealing with uncontrolled or resistant hypertension. This clinical challenge remains a leading, inadequately addressed global cause of death and loss of quality of life. With today's positive top-line announcement, we've made substantial progress towards meeting this significant unmet medical need. I'd be remiss if I didn't acknowledge and say I'm grateful to the participating trial investigators and subjects for their enthusiasm and commitment to the development program for lorundrostat.
I'm especially grateful to the Mineralys team for completing and reading out two pivotal hypertension trials today. Their dedication and hard work has allowed us to get to this significant milestone for Mineralys, for our shareholders, and, most importantly, the patients in need of transformative innovations. Our Chief Medical Officer, Dr. David Rodman, will now take some time to review the top-line data from the Launch-HTN and Advance-HTN trials.
Thanks. Thanks, Jon, and good morning. I'm going to share some more detail about the top-line results from our two successful trials, Launch-HTN and Advance-HTN, which are intended to provide the core data set for our anticipated new drug application. The primary efficacy analysis in the phase III Launch-HTN trial was pre-specified at six weeks of treatment. This trial was intended to evaluate the efficacy and safety of lorundrostat when added to existing background medication over a 12-week period. The traditional threshold for determining clinically meaningful change for the purpose of new drug registration has been approximately 5 millimeters of mercury placebo-adjusted reduction in blood pressure. The observed treatment effect far exceeded that threshold. Absolute reduction of 16.9 millimeters of mercury and placebo-adjusted reduction of 9.1 millimeters of mercury in automated office systolic blood pressure were observed with a p-value of 0.001.
At the end of treatment at 12 weeks, the benefit was sustained and potentially increased with an absolute reduction of 19 millimeters of mercury and a placebo-adjusted reduction of 11.7 millimeters of mercury in the 50-milligram arm, with a p-value of less than 0.0001. In the lorundrostat dose escalation arm, the week 12 reductions in systolic blood pressure were absolute 15.7 millimeters of mercury and placebo-adjusted 8.4 millimeters of mercury with a p-value of 0.0016. There was an appearance that the effect size in the lorundrostat dose escalation cohort was lower than in the 50-milligram dose arm. However, this was not confirmed at the individual subject level in those whose dose was increased, and there was overlap in the grouping confidence intervals in the 50-milligram lorundrostat and with the 50-100 milligram dose escalated arm.
Therefore, we did not see a benefit to increasing the lorundrostat dose in individuals who failed to achieve their target blood pressure goal with the 50-milligram dose. This confirms that 50 milligrams is the optimum and maximum efficacious dose level. A finding in Launch-HTN observed also in Advance-HTN, the reduction in systolic blood pressure was sustained with potential further reduction at the end of treatment at 12 weeks compared to the earlier time point. This adds confidence that the treatment response is robust and likely to persist and confirms again that the 50-milligram once-daily dose is an efficacious starting dose. Analysis of key secondary outcome measures in both trials was done at the earlier time point when all subjects in the active arms were being treated with the 50-milligram dose, providing more statistical power for the smaller subsets.
In Launch-HTN, lorundrostat worked equally well in those taking two baseline medicines and those taking three or more. Lorundrostat worked equally well in both men and women, as well as in white and black subjects. We are pleased that approximately one quarter of study subjects in Launch-HTN were black, a population with particularly high incidence of poorly controlled hypertension and a high incidence of major adverse cardiovascular events. With respect to analysis of the effect of obesity, we treated BMI as a continuous variable, and no statistically significant effect was seen. It is important to note that lorundrostat worked equally well in overweight subjects and obese subjects, confirming the utility in a broad range of patients.
We look forward to reviewing results of additional pre-specified supplementary analysis using more direct measures of abdominal obesity, namely waist circumference and waist-to-hip ratio, as well as serum biomarkers including leptin, adiponectin, aldosterone, and renin. We anticipate there will be a future presentation and publication reporting on these analyses. Equally important to developing a drug for difficult-to-treat hypertension is having an acceptable safety profile and good tolerability. We believe the clinical safety and tolerability findings from both pivotal trials, including the low incidence of serious adverse events and the low incidence of changes in serum potassium, eGFR, and serum cortisol, support a favorable benefit-risk profile in both the real-world use case studied in the Launch-HTN trial and in the Advance-HTN trial in established uncontrolled or resistant hypertension.
Regarding safety in the Launch-HTN trial, there were nine subjects, or 3.3%, with serious adverse events, eight of which were treatment emergent in the placebo arm. In the 50 milligram and in the 50-100 milligram arms, there were 13 subjects, or 2.4%, 12 of which were treatment emergent, and two subjects, or 0.7%, all of which were treatment emergent, respectively. There were five subjects, or 1.9%, with treatment emergent adverse events requiring dose discontinuation in the placebo arm, and 14 subjects, or 2.6%, and four subjects, or 1.5%, respectively, in the 50 milligram and 50 milligram-100 milligram arms. The incidence of elevations in serum potassium of greater than 6 millimole per liter was 0.7% in the placebo arm, 1.1% in the 50 milligram once-daily arm, and 1.5% in the 50 milligram-100 milligram arm, and resolved soon after discontinuation of lorundrostat.
The primary efficacy analysis in the phase III Advance-HTN trial was at 12 weeks of treatment. This rigorous trial in confirmed, uncontrolled, and resistant hypertension was designed to evaluate the efficacy and safety of lorundrostat when added to optimized background medication over 12 weeks. As Jon mentioned, we're excited that the phase II Advance-HTN trial will be featured in the late-breaking clinical research session at ACC 2025 later this month, and additional trial results will be presented there, as well as in an upcoming publication. In subjects treated with lorundrostat, we observed a clinically meaningful reduction in systolic blood pressure at week four and at the week 12 pre-specified time point for the primary analysis of efficacy, a highly statistically significant 7.9 millimeters of mercury placebo-adjusted reduction in systolic blood pressure in the 50-milligram once-daily arm.
The incidence of elevations in serum potassium of greater than 6 millimole per liter was approximately 5.3% in the 50-milligram arm and 7.4% in the 50-milligram to 100-milligram arm. As in the Launch-HTN trial, potassium elevation resolved soon after discontinuation of lorundrostat. There was one death in a subject receiving 50 milligrams of lorundrostat that was deemed not related to study medication by the site investigator and the medical monitor. We believe the efficacy and safety findings in this especially rigorous hypertension trial support a favorable benefit-risk profile for lorundrostat in patients with confirmed uncontrolled or resistant hypertension. I'm now going to turn the call back over to Jon Congleton. Dave, thanks.
The lorundrostat development program, as you see here, has really achieved two significant milestones today: the completion of what you just heard Dave talk about, the highly rigorous Advance-HTN trial with the 7.9 millimeter mercury placebo-adjusted change, and the real-world study, Launch-HTN, which is now completed with a 19 millimeter mercury absolute change and that 11.7 millimeter mercury placebo-adjusted change with the 50 milligram for both. We're obviously thrilled with the success, the completion, but certainly the outcome. As I said at the beginning, there's a lot of work behind these clinical trials. We felt we had the right plan, the right team, and are thrilled now with the results we're able to report with this program. We have additional studies that are ongoing and underway. We have the Explore-CKD trial looking at hypertension and CKD for patients with an eGFR down to 30.
We're still on track for top-line data in Q2 of this year. Earlier this year, we announced the OSA in hypertension study. That study has initiated at this point. We're still waiting for the early roll of patients coming into the trial, and once we get a sense for the feasibility and the timing, we will update on guidance for that. As we progressed the clinical development program for lorundrostat, we maintained a focus on the market opportunity, the physician interest, and the payer needs for novel innovations in the treatment of hypertension. In our market research, and as we shared with you, a clinical profile of 8-10 mm mercury reduction in systolic blood pressure with a modest impact on potassium and a well-tolerated profile resonated with payers and physicians as an ideal option, certainly in fourth line and potentially with a targeted approach in the third-line treatment.
Now, with the data that Dave just shared with you today, lorundrostat clearly provides clinically differentiated value in that fourth-line position for those resistant hypertension patients. As we've done the analysis, that breaks down to about 10 million patients in the United States. The benefit demonstrated in patients on two background hypertension medications in our clinical program potentially supports broader third-line usage for the approximately 10 million subjects with uncontrolled hypertension than we'd originally planned. As we continue to analyze the data, we will continue to evaluate predictors of an enhanced response to guide access and demand for the patients looking to address their unmet need, particularly when their condition is driven by dysregulated aldosterone.
In September of 2023, we saw the initial signs of promise with lorundrostat, with a Target-HTN proof-of-concept trial results demonstrating a meaningful clinical benefit that was safe and well-tolerated once daily with a 50-milligram lorundrostat. The top-line data today from our two pivotal clinical trials provides further evidence of the consistent clinical benefit that lorundrostat has in uncontrolled and resistant hypertension patients, with approximately 30% of all hypertension patients dealing with ramifications of elevated or dysregulated aldosterone. We believe the clinical profile of lorundrostat as a best-in-class aldosterone synthase inhibitor could have the potential to extend and improve the lives of millions of patients. We will continue to advance our commercial and partnering activities to ensure that we maximize the value of this novel, best-in-class, and potential first-to-market aldosterone synthase inhibitor, lorundrostat.
We're clearly excited about the new clinical data that we've shared with you today. We've given you a lot of information. We look forward to your questions. With that, I'll ask the operator to open up the call for questions.
Thank you. We'll now be conducting the question-and-answer session. If you'd like to ask a question at this time, please press star one from your telephone keypad, and a confirmation tone will indicate your line is in the question queue. You may press star two to remove yourself from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the Star keys. One moment, please, for our first question. Thank you. Our first question today comes from the line of Umer Raffat with Evercore ISI. Please proceed with your questions.
Morning, guys. Congrats on the data, and thanks for taking our questions. I have a few today, if I may. Perhaps first, just wanted to understand your broader thought process around, is this an asset you think you can take to commercialization yourself? I know there's a lot of commercial background for much of the management team, but just curious if you think you do or don't need a partner. Second, I know the bigger trial had AOBP as a primary endpoint. Curious if ABPM was tracked as well and if you could speak to the consistency. Speaking of consistency, could you remind us resistant versus uncontrolled patients an`d obese, what you saw there? Finally, any thoughts on hyperkalemia with a definition on 5.5 threshold? Thank you very much.
Yeah, Umer, thanks for the questions. Make sure that I capture them all. If I miss one, please let me know. Your question, could we go commercial or partner? I think the answer is, with the kind of data that we're seeing here, the profile that's emerged, and the profile to me is not just the robust reduction in blood pressure that we saw of 19 absolute and 11.7 adjusted, but it's the hyperkalemia as well. We're looking at 1% in the level that is probably concerning for physicians. So it's really a great profile and a nice balance of efficacy and safety for patients and well-tolerated.
Taking that forward into the fourth line, certainly third line, yeah, I could see a path where Mineralys can do that because, as you saw on the slide, about 47,000 physicians in the United States control about half of that third and fourth-line prescription volume. That said, and it's why I acknowledge the partnering, to really maximize the value of an asset like lorundrostat, we would be looking for a partner to do that in the United States. Certainly, and we've said this before, ex-U.S. I don't envision Mineralys being the commercial driver in Europe and Asian markets. That'll be a key part of our strategy. When you have an asset like lorundrostat, yeah, there's clearly a path for Mineralys to tap into that value.
If I go to your next question, in Launch-HTN, because that was our real-world study, in other words, how lorundrostat would be used in the marketplace, we did not do ABPM. Launch-HTN was about four times bigger than Advance-HTN. Doing the kind of rigor that we put on Advance-HTN with the 24-hour ambulatory just would have been a bit challenging in that trial. As we saw in Target, we've seen really nice concordance between ABPM and AOBP. I think for Launch-HTN, with that real-world measurement, we're in good shape. Umer, you had a question about resistant versus uncontrolled as it related to obesity. I would say at this point in time, with the analysis we've done at a broad level, as Dave said, the BMI was not predictive relative to response in Launch-HTN.
David built out some additional endpoints that, frankly, are probably using better metrics for measuring visceral adiposity, and that's waist circumference and waist-to-hip ratio. We're going to be doing further analysis on that and sharing that data likely in future publications. I think the overall good news that Dave made was, whether overweight or obese, you're clearly seeing a robust response and helping patients get to their goal, ideally, and reducing their overall cardiovascular risk.
Thank you so much, Jon.
Yeah, thanks, Umer.
Thank you. Our next question is from the line of Richard Law with Goldman Sachs. Please proceed with your questions.
Hey, guys. Good morning and congrats on the results. A couple of questions for me. Given that Advance was designed with the state-of-the-art feature that you mentioned, why do you think we're seeing the efficacy and safety differences between the study where the largest results look better and have lower hyperkalemia rate? I'll save the other question for later.
Yeah, Rich, thanks for the question. Let me address the efficacy question. I may have Dave talk about the potassium profile, which is still well within the, from our standpoint, acceptance from a market standpoint, the 5%. From an efficacy standpoint, over the last year, two years, I've been asked to kind of hedge for these two studies, where do I think the efficacy will be? We have consistently guided to 8%-10% as a win. And hitting that target with Advance-HTN and exceeding it with Launch, I think it's a very positive outcome. In the case of Advance, there were two factors working there. On the one hand, we had truly confirmed uncontrolled and resistant patients based on the fact that we were putting them on a high-dose optimized AHA-approved background treatment, tracking them for three weeks, using the gold standard measurement.
We were really, with that study, weeding out potential apparent hypertension patients and getting the very difficult, truly confirmed hypertension population. We were putting lorundrostat to the test with those very difficult-to-treat patients. On the other hand, we said, "Maybe we're enriching for aldosterone because you've hit a lot of the different pathways that are driving their hypertensive condition, and yet they're still not at goal." I think the answer, Rich, is it was probably a little bit of both. If you think about comparative studies of Advance's rigor, think about renal denervation with the RADIANCE trial, think about aprocitentan with the PRECISION trial, where I think there was 5 millimeter and 4 millimeter mercury placebo-adjusted change. With Advance-HTN, we're effectively seeing an 8 millimeter mercury placebo-adjusted change.
I actually look at Advance as an equally robust outcome in a really difficult-to-treat patient population that likely has aldosterone as a part of their condition. As far as the potassium, maybe a difference between Launch and Advance, let me have Dave talk to that a bit.
Hi, Rich. It's a good question, and we expected this, as did our advisors. The main difference is the background medication. In the Launch-HTN trial, the subjects came in on whatever they were on, as long as there was a thiazide diuretic in the regimen. In the Advance-HTN trial, we stipulated they needed to be on really the highest dose of the most long-acting and potent angiotensin receptor blocker, or ARB, olmesartan. I'll remind you that these ARBs increase potassium, and they decrease your ability to clear potassium. You would expect a bit more increase in potassium. In particular, this is what we refer to as a double RAAS therapy, upstream and downstream, angiotensin and aldosterone.
This combination was tested 20 years ago, combining ARBs and angiotensin-converting enzyme inhibitors, and it was abandoned because there wasn't much benefit over just the ARB, and the potassiums were unacceptable. Here, we seem to have achieved that goal without much of a potassium liability. Now, I'll finalize by saying we spoke to a number of experts because this regimen is going to be particularly useful for them. What their response was, "We're not too concerned about high potassium. We will use potassium binders, which we're very comfortable with. These patients need blood pressure reduction.
I see. Got it. Another question on how should we think about the lower efficacy for the 50 mg arm - 100-mg arm compared to the 50-mg arm? Do you think the up titration provided any benefit?
Yeah, Rich, I think if we think about the entire program for lorundrostat, going back to Target-HTN, where we really didn't see a difference from an efficacy standpoint between 50 milligram and 100 milligrams, these results with Advance and Launch really confirmed the 50 milligram, as Dave said, as the dose. We went into this program with that in mind. What we wanted to test was, would the opportunity to titrate to 100 provide any additional benefit? As Dave said, there is overlap within the confidence intervals between these two. If we think about the design of Launch, and it's important to point this out, the design of Launch was to randomize 1 to 2 to 1. We had twice as many patients in that 50 milligram alone arm without the complications of 50 to 100 titrated.
That gave us really strong assurance of that 11.7-millimeter mercury placebo-adjusted change as really the most accurate assessment.
Okay. Got it. I am going to squeeze in one more. Do you plan to present the detailed results for both trials in one conference, or would these be spread out over multiple conferences? Thanks again.
Yeah, thanks, Rich. As we said, we're really thrilled with the acceptance of Advance-HTN as a late breaker at ACC. I would anticipate seeing more detail about Launch-HTN at a future medical conference as well as peer-reviewed publication.
Great. Thanks.
Our next questions are from the line of Seamus Fernandez with Guggenheim Partners. Please proceed with your questions.
Hey, guys. Thanks for the question. Congrats on the data. A couple of quick questions. Just as you look at the sort of pooled overall 50-milligram dose performance, can you just remind us what we're seeing in terms of the maybe you can't talk about Advance, but in Launch-HTN, if the data basically came in above a sort of 10-millimeter threshold, I just want to ensure that when we're looking at the primary endpoint, which, again, I know in that study was at 6 weeks, but at 12 weeks, what are we seeing in terms of the overall pooled dataset if you were to pool the 50-milligram dose without inclusion of the 100-milligram dose across the two arms? We're just getting a lot of questions from investors on that front and what that would have showed. Second question is just the path to filing from here.
What are the gating factors? What additional data do you need? Six-month safety follow-up, etc., prior to potential filing with FDA? Have you satisfied, from your perspective, other than the six-month follow-up, the ability to file and any kind of timelines you can offer? Along those lines would be helpful. Just the last question. In terms of the 50-milligram dose being kind of the core dose, is that much different from other hypertension drugs? Do you feel that there's any need at all to request a 100-milligram dose as part of the label, or will you only pursue 50 milligrams? Thanks, guys.
Yeah. Same as thank you. Let me have Dave start off with the question on the 50 mg pool, and then I'll give you some color on the path to filing and how we're thinking about the doses that would likely be in the label. Dave?
Thanks for the questions, Seamus. We haven't reported on the pooled data, and that'll be part of a subsequent report in the publication. I can guide you that, remember, there's twice as many subjects in that 50-milligram arm than the 100-milligram arm. You can get a rough idea from just doing a weighted average. Two-thirds at that 11.7 and then one-third at the lower number, and it's above 10.
To your question on the path to filing, obviously, we're thrilled with the data that we have for Advance and Launch and the active control. Even the Target data will be part of the overall safety package that we'd put forward. Obviously, the open label, long-term safety, it's actually out to about 48 weeks or 12 months is what will make up the safety package that we'll put forward. We're continuing to collect that. I think everything else is on track as far as for the program. We haven't provided guidance at this stage. There's the ability to do an update of safety data once you've made the filing, but we want to make sure we have the proper balance and the majority of that safety data within the initial filing for the package.
As we continue to progress the program, we'll provide guidance as we have clarity on that. Lastly, as far as the dose that we anticipate having in the label, I would say at this point, the evidence is pretty clear from Target, from Advance, and from Launch. The 50 milligrams is really delivering the kind of efficacy that's going to make a big difference in patients' lives and do so with a really nice safety and tolerability profile. I would remind people, we also have the 25-milligram dose. That's something that's been available as a down titration through the Pivotal program. It's the key dose that we're focused on in our Explore-CKD study. It is anticipated that the label will have both 25 milligrams and 50 milligrams within it.
At this point in time, I would say it's unlikely that the 100 milligrams would be a dose that we feel would be even necessary for prescribers and patients.
Great. Thanks, guys. Congrats again.
Yeah. Thanks, Seamus.
Our next question is coming from the line of Annabel Samimy with Stifel. Please proceed with your questions.
Hi, guys. And congratulations on some great data. Thanks for taking my questions. Just, I guess, a broad question. Given that lorundrostat is working so well across all the different populations, obese as well as overweight, do you expect physicians—how do you expect physicians to really be identifying those patients who specifically have hyperaldosteronism? Does it complicate their diagnosis, or does it make it easier for them? They don't have to consider that anymore. Is this going to be, I guess, more difficult for the general practitioner or the primary care practitioner, or are you keeping this still in the specialist cardiovascular cardiologist population who are really treating the third, fourth-line patients? I guess that also speaks to the question of hyperkalemia rates.
Will this be something that, I guess, the general practitioner will be concerned about, or is it still, again, in the cardiologist's office, and they know how to manage this very well? I guess, last question is, can you discuss the AEs of special interest? Can you characterize those at all? Is there anything there that we need to be thinking about? Thanks.
Yeah. Thanks, Annabel. Let me make sure I touch on all these. Identifying the patients with aldosterone, is it easier or harder? Is it a GP? Is it a cardiology? I'll maybe step back a little bit more broadly from that. If you see what's going on in the medical community now, progressively, there's more and more interest and attention being paid to aldosterone. And frankly, the medical community acknowledging that they're underdiagnosing that. You're seeing more inclusion in guidelines, speaking to aldosterone about how to test it, how to evaluate it. The medical community, I think, is rapidly becoming attuned to the prevalence that we've discussed with you in the past is likely around 30% of all hypertension patients having some form of either dysregulated or elevated aldosterone.
If I think about how does that awareness in the market match up with the data that we're seeing today, I think it's becoming really evident that in that resistant population, I'll talk to that one first. Fourth line, that lorundrostat is going to become, I think, a pretty rapid clear choice for those patients. We've seen in published literature before, as you move from various earlier stages of hypertension to resistance, that prevalence grows higher. I think, again, lorundrostat is going to be a clear choice in that space. For third line, I actually think, as I said in my remarks, that that overweight and obese population is going to continue to be a really informative group, even at the GP level. We're not giving up on the obesity. I think the BMI, again, was informative in Target-HTN.
It did not show the signal in the pivotal program, but we're going to continue to look at other more sensitive measures of visceral adiposity that could inform that. Given the data that we saw in both uncontrolled and resistant in the Pivotal program, I think there's a clear place to use lorundrostat even at the third-line position. I think what makes it even easier for a general practitioner or primary care population to not only use lorundrostat fourth line, but third line is that 1% hyperkalemia rate that we saw in Launch-HTN. That's the real-world setting, right? That's where patients are coming in. They're on their existing background meds.
In the primary care, they tend not to be pushed on background dose nearly as high as what we saw in Advance-HTN, which is where your specialist, your cardiologist are going to be going. For a primary care doc to see that 1%, we did not even test that level of hyperkalemia because we did not anticipate it being that low. We feel very confident that the efficacy that we have seen, coupled with that safety, is going to really open up the possibility for primary care prescribers to work with the drug. Again, I think for the specialists who are dealing with those very difficult to treat, certainly resistant hypertension patients, that is why we did Advance-HTN.
We wanted to make sure that we did or had within the clinical dataset of lorundrostat a truly rigorous confirmed hypertension trial to address the needs of those specialists and to basically show them what lorundrostat can do in the populations they're treating. We've also discussed this in the past. Advance-HTN's rigor was by design to hopefully enable us to get lorundrostat into the hypertension guidelines. I can't speak to how that's going to be interpreted or the placement of treatment, but certainly the rigor of that study, I think, will be recognized by those guideline physicians. As far as the AEs of special interest, Dave walked through that. I would characterize them as really more the on-target. We are talking hyperkalemia, hyponatremia, and maybe changes in eGFR, but all within the acceptable range.
Okay. Great. Thank you very much.
Thanks, Annabel.
Our next questions are from the line of Mohit Bansal with Wells Fargo. Please proceed with your questions.
Good. Thank you very much for taking my questions. Thank you and congrats on the data. I have a question regarding the real-world implications of these hyperkalemia rates. Dave, if you could help us understand how physicians manage something like Spiro, what time frame point after the first dosing this got tested for hyperkalemia? Do you expect the management of lorundrostat being any different from what we see with other MRAs or other agents like that? Thank you.
Thanks, Mohit. The first question was, what are the implications in general of these rates? Compared to spironolactone, these rates are dramatically lower. spironolactone has had a really hard problem getting used as fourth line where it's supposed to be used. I think in that space, this is going to be seen as a really useful new tool. The question was, how do physicians manage this? Within two weeks of starting the drug, you'll see the maximum change in potassium. Typically, you write the prescription for 50 milligrams. Two weeks later, they come in just for a lab test, a quick one. It can be at their neighborhood blood draw. The physician looks at it.
In general, if it's a grade one increase, in other words, above normal but certainly below six, then for the most part, you would observe and follow and get another measurement. As Jon mentioned, though, we are carefully studying the 25-milligram dose as well. From the data that we had in the Target study, we are confident it will be effective, and it will give physicians another tool, which is to decrease the dose and then bring them back in. It should still be effective. Was there another part of your question?
Yeah. Let me add to it. Mohit, I think I agree with everything Dave said. I think if you think of the practice of a primary care doc, they're attuned to doing this, what Dave just described, and they're attuned to that even with ACEs and ARBs. We know that ACE inhibitors, the angiotensin receptor blockers, have kind of a similar profile. A couple of weeks after initiation, a slight rise in potassium that then stabilizes over time. What we're asking physicians to do is nothing different than they're currently doing with their hypertension patients right now with the existing treatments they have.
Got it. If I could ask one more, what would be the—you just said that there was a higher dose of olmesartan or ARB in this trial. What would you see or what would you expect in terms of higher potassium levels on this kind of dose in clinical settings?
Yeah. I don't know that you're asking what do we typically see if we're almost starting alone as it relates to potassium?
Yeah. At the highest dose. Yeah.
Yeah. I don't know that I have specific data on that, Mohit.
Okay.
I can tell.
I can find that.
I can tell you real quick that for Advance-HTN, that three-week titration period before subjects could be randomized, they needed to be stable on their electrolyte measures. We haven't investigated that as far as what was the rise within Advance.
Got it. Thank you. Thank you, Jon. And congrats once again on the progress. Appreciate it.
Yeah. Thanks, Mohit.
Our next question is from the line of Tim Anderson with Bank of America. Please proceed with your questions.
Hi. This is Alice on for Tim. Thank you for taking our questions and congrats on the data. Following up on your comments on the obesity signal, when do you plan to share those additional analyses on waist circumference and other metrics? I know you just touched on it in one of your previous responses, but how important is it commercially for you to demonstrate a signal there? I have a follow-up.
Yeah. I think we'll obviously be doing the analysis and plan on sharing it at a future Congress and peer-reviewed publication. I can't guide as far as the specific timing, but it's obviously something we're going to continue to analyze. It was a part of our—from a commercial standpoint, I don't know that it was a part of the resistant population. We've always viewed lorundrostat and a safe, well-tolerated aldosterone-directed treatment being a difference maker for resistant hypertension population writ large. In the third-line population, where I would say typically you see ACE or ARB first line, diuretic second, and a calcium channel blocker like amlodipine third line, we felt that obesity could be a way to guide to subjects that are going to get a better response with lorundrostat than amlodipine. We're going to continue to evaluate that.
As you heard Dave say, we have different measures and maybe more sensitive ones for visceral adiposity. We're going to look at other markers such as leptin, certainly looking at aldosterone and renin. I would say with the data that we have shown now with Launch-HTN, this is a very competitive profile writ large for third line. I think it basically enables for both not only the obese but also the overweight potential benefit for a safe and well-tolerated means of getting to their goal.
Thank you. On the hypertension guidelines, assuming approval, when do you think could be the next opportunity to get lorundrostat into the hypertension guidelines? Finally, now that we have your top-line data, how should investors think about the upcoming AstraZeneca/baxdrostat readout? Any differences that you would like to flag for investors? Thank you.
Yeah. On the guidelines, it's hard to opine on the timing of that. We're obviously thrilled that we've got a clinical package that I think will meet the rigorous criteria of those guideline committees. I know historically, as new innovations and new data has come forward, they've tried to reflect that within the guidelines, but it's difficult for me to opine on the timing of that. As to the AstraZeneca data, I don't know that I'm here to opine on that. We're just thrilled with, frankly, the consistency of the profile that we've seen now in three clinical studies with lorundrostat, the magnitude of response, the kind of safety and tolerability profile that's emerged. Again, we've been very bullish on lorundrostat. We think the half-life of this molecule, the selectivity makes it a best-in-class ASI.
Having these two data readouts as part of our pivotal package now certainly gives us an opportunity to move rapidly forward to introduce it to patients.
Thank you so much.
The next question is from the line of Rami Katkhuda with LifeSci Capital. Please proceed with your questions.
Hey, guys. Congrats on the data, and thanks for taking my questions as well. Two quick ones for me. I guess first, do physicians utilize the high olmesartan dose that was used as part of the standardized background regimen in Advance as part of the real-world setting, or do they just generally add another treatment? Secondly, I know you can't probably go into details, but were there meaningful differences when comparing systolic blood pressure reductions with ABPM versus AOBP in Advance? Could you remind us of differences in those measurements in historic studies?
Yeah. Rami, to your first question, the high dose, I think that's what makes Advance somewhat distinct from Launch. I think the real-world setting, it's rare that physicians push to max dose. It's not just ARBs. I think it's across the board. Part of that reason is to avoid adverse events or side effects. It becomes a tolerability question. That's why I think the Launch-HTN is such a critical part of the data story for lorundrostat because, again, that's how the drug will be used with a variety of background treatments. I'm not saying that there weren't subjects in Launch that weren't more maximally treated, but it's that variety of background meds that we've now seen lorundrostat have that 19 millimeter mercury absolute reduction and the 12 millimeter or 11.7 millimeter mercury placebo-adjusted change.
I think that's really the benefit that lorundrostat can provide there. As far as the 24-hour and the AOBP, I really can't opine on what is going to be presented at ACC at this point. We're obviously thrilled with the partnership with the Cleveland Clinic, and Luke will be sharing information about Advance-HTN that we think will be really informative to the medical community writ large about the profile that we're seeing there. As far as distinctions between 24-hour measurement and AOBP writ large, as you recall, in Target- HTN, we saw pretty tight concordance as far as response to lorundrostat between those two measures.
In some historical constructs, there's a view that the change on a drug in AOBP may be a couple of millimeters of mercury higher than in ABPM, but I think that's a little bit of a misnomer or an artifact, if you will. I don't know that there's always a great deal of separation between the two. I think the key is having well-controlled design of study and measurement. Rami, you know the lengths that we go to to make sure that our in-office measurement is as reflective of reality as we can. I think the concordance like we saw in Target- HTN is maybe reflective of what we've seen in the past.
Got it. Thank you and congrats.
Thanks, Rami.
Thank you. The next question is from the line of Matthew Caufield with H.C. Wainwright. Please proceed with your questions.
Hi. Good morning, guys. Great to see this data. Congratulations. You had just mentioned evaluating the additional obesity criteria for going forward. I was thinking from a mechanism standpoint, is there any sense of what could have impacted not observing superior benefit among the high BMI patients, at least at this stage? Thanks again.
Yeah. Hi. This is Dave again. It's a good question. We did have a poster at ASN last year that showed what it looked like in the Target-HTN when we did this treating the BMI as a continuous variable. In other words, a regression line instead of a cut at 30. We did see a trend from all the way at BMIs of 23 and up that the drug worked, and it worked progressively better. It may be technique-wise. I do think the consensus now is this is about fat around your belly. Men have that more than women, and you really need to measure the circumference of the abdomen or the ratio with the hips. We have that plan. That's going to give us a better index on that. I really don't think I should speculate any more than that about the differences.
Okay. Fair enough. That's helpful. Thank you, guys.
Thanks, Matt.
Thank you. At this time, I'll turn the floor back to Jon Congleton for closing remarks.
Yeah. Thank you, operator. Thank you, everyone, for joining us today. Obviously, we're very excited about the data that we've announced today. A lot of work went into this. We're thrilled with the outcome. The overall progress that we've made over the last four years moving from the proof of concept Target-HTN, now with the readouts of Advance-HTN and Launch-HTN, and really the concordance of data that we continue to see with lorundrostat, the meaningful difference it's making on systolic blood pressure and with the safety and tolerability profile, we think there's significant opportunity with this potentially transformative agent. Thank you. We look forward to keeping you apprised on our future progress. With that, we'll close the call. Thank you, everybody.
Thank you. This will conclude today's conference. We thank you for your participation. You may now disconnect your lines at this time.