Eugene Sullivan: Yeah. And just to be clear, I think what I was commenting on before were the patients with study drug related adverse events and that and that, in fact, when they’re worse cough, doctors tended to identify this study drug related, you know that it’s tough to the investigator to decide do I think a study drug related or not, and they tended to attribute cough to the drug more frequently in TPIP and did not attribute it to the placebo. And again, that’s probably related to the temporal nature. They had a lot of these patients have an underlying cause of that would be just representative of the disease. So just to just to clarify what I meant on that. But to your broader question, we are not seeing any particular safety finding that’s that would be unique to TPIP something unexpected at all.
And certainly nothing that’s impinging upon I dose escalation because we’re getting so many people up to really the maximum or we also release that the number of patients who got to the second second to the top dose and done. And that was pretty high, too, that if you if you go to that, it’s 90% of patients. So we’re not seeing problematic AEs that limit the dose escalation on and we’re not seeing any novel safety events that would give us concern that something unique to TPIP.
William Lewis: And I would only add that I think you just have timeframe we have for that for that titration, Ritu, is five weeks. So in the real world, physicians could continue to dose escalate over perhaps a longer period of time and might find greater success. But backbone here is 80% of patients are getting the maximum tolerated dose of six 40 in this study in the ILD study and 90% of them are getting to the penultimate level, which is just a remarkable outcome from our point of view.
Operator: Your next question comes from Jeff Hung from Morgan Stanley.
Jeff Hung: Thanks for taking my question. On particular, particularly based on the data, can you just comment if you see any evidence of disease modification? And then I have a follow-up.
William Lewis: Gene, do you want to address that?
Eugene Sullivan: Yes, by disease modification, I presume you’re referring to on the underlying on pulmonary fibrosis, which I know that that was a was the observation made in the INCREASE trial that there may be some evidence of the effect on the pulmonary fibrosis and United Therapeutics is currently conducting a large trial that trial to detect that on where we might see any effects on the underlying disease process would be lung function and we have not analyzed that data yet. However, it’s extremely unlikely that we would see any evidence of that with such a small study and such a small placebo group. It’s only 1010 patients, we really the three to one randomization was and intended because what we really wanted to do, it’s just got some safety information to give this drug to patients with PH-ILD and make sure nothing untoward happened and that’s what we saw.
So we don’t expect to see any information that could inform whether or not on treprostinil impacts the on the pulmonary fibrosis.
Jeff Hung: Okay, great. And then you started education efforts for brensocatib fairly early, but can you just talk about how far that’s come in and how much more education you think is still needed for physicians for potential launch?
William Lewis: Well, I’m happy to report that we have that’s the similar experience of being a first in disease drug and the first ever approved drug for the uricase were used in refractory MAC patients. So that experience forms our approach once again to the larger opportunity that would be represented by bronchiectasis using brensocatib into that medical education. It got underway with the American Thoracic Society really last year at this time and has been ongoing. And that will continue to read through our expected launch in the US, which would be the middle of 2025. In parallel to that, we are also I right now started at the end of last year, working on the market access front to make sure that that education on the disease state is handled appropriately and that everybody has informed our experiences that by doing these things and people are at a much better place to understand if there is a drug that is approved and it has an effect, people know how to place that into context and what that would really represent for patient care.
And that’s the purpose behind all of it. But certainly starting early when you’re first and disease is crucial, and we’ve been doing that, and that’s a critical investment we’ve been making. I’ll also report that on the commercial front, the progress with regard to bringing additional resources in first in the US And then in Japan and Europe is also underway at the area director and regional director level on those critical promotions and hires have taken place. And I will say I am shocked at the degree of interest that is coming from the outside world for these positions. When we indicate that there might be a position available, we are getting scores of candidates signing up to trying to gain access to the opportunity side of everybody feels what is coming is incredibly exciting and want to be a part of that appropriate disease education and ultimately that the commercial launch of the drug should everything go as expected by the middle of ’25.
Hopefully, that’s helpful.
Operator: Your next question comes from Liisa Bayko from Evercore ISI.
Liisa Bayko: Hi, guys. Congrats on the TPIP data. Just a couple of follow-up questions on ASPEN. It kind of play out over to a saying, but in the more high level way. I noticed there was a lot of patients in your baseline paper from the Latin America region was, I think, more than a quarter of the population, which they seem to have milder disease. Can you talk about your comfort level, making sure like some specific large groups like that are well balanced across the arms that That’s my first question. Then my second question relates to how we can think of a quiet period around the data. Are you planning on a kind of a couple of the quiet period a couple of days. Just wondering if we can now if we stop hearing from you guys, if we might think data is coming back.
William Lewis: I’ll take the second question first, just to tell you that on when when the moment comes, I think that the certainly will be we’ll be going quiet, but I think that is more a byproduct of us needing to take a step back and make sure that as I mentioned earlier, the quality of what we’re doing is meeting the standard that the hierarchy here is very clearly and always has been quality first speed, second budget, third, in that order of priority in terms of making sure we produce of the best possible outcome here. So I don’t know to be transparent how long it will take from the moment that we decide we’re ready to lock the database to the moment that we’re analyzing the data and interpreting the results. Obviously, some of that will depend on the results themselves.
And but so it’s hard to give guidance, Lisa, as to how long we would be quiet. It’s just it could be any length of time. And most importantly, I would not interpret a longer period of silence as meaning that there is in any way something wrong. Indeed, we are very focused, as I said before, on the quality, and that may be of something that we just want to refine. And so so that would be my answer to that. With regard to the concentration of patients in different parts of the world. We remain very comfortable with the profile of what we have recruited into the study. There is remarkable, I would say, consistency in our experience with this trials so far based on our careful monitoring of regions on a weekly basis down to the country level and to ensure that there weren’t significant deviations or aberrations from some other areas of the world.
And so that’s been an ongoing process that we’ve had. I think what we saw in terms of concentration from Latin America is not in any way on problematic or concerning. In fact, I think I don’t know how to respond to the comment about milder disease because that that is not something that we would identify as being necessarily the case. But I can tell you we feel very good about the baseline demographics here and the distribution around the world. Hopefully that answers the question.
Liisa Bayko: Did you stratify for Latin America specifically or does that just go into rest of world through application?
William Lewis: We didn’t stratified in that sense to the best of my knowledge. Nobody else can direct me if I’m wrong, but we do obviously track now where patients come from, and we can certainly cut the data that way should it become necessary to do so.
Liisa Bayko: All right.
Eugene Sullivan: Let me let me step in here for just a second. We actually did stratify based on region. Latin America is on the list, but other regions as well. Western Europe Eastern Europe, et cetera.
Operator: Your next question comes from Jennifer Kim from Cantor Fitzgerald.
Jennifer Kim: Hey, guys. Thanks for taking my questions. And congrats on the cheaper data, maybe to start with friends. So I think the answer is yes, but I just want to confirm, is it fair enough to say that the data is coming at ATS, just given the timing of deadlines. And then also to follow up on the last question, when you’re monitoring on a regional basis on a blended rate basis, are you saying that the rates are sort of in line with what you would expect on a regional basis? And does that also take into account the differences in I guess, macrolide background regimens looking at Japan, I know we saw in the paper there’s a much higher use of that, for example,
William Lewis: So I’m not going to comment on the timing of the data anymore than I already have. We’ve given the window from mid-May to the end of June and sometime in that timeframe, we’ll produce it in regard to the specific question about what we’re monitoring on a on a country basis. I think there are a lot of things we look at. I don’t go into the specifics of how we what we’ve seen or what we conclude or any that interpretation. I would just encourage everybody to not over-interpret comparisons from the past or or other studies. I think the simple answer is we’re proximate enough to the actual data from ASPEN to just sort of wait for that data. I don’t think it is possible and we have much better information than all of you to interpret what these results will really be until we unblind, we feel good about the direction of everything that is contained within the study.
We see remarkable consistency with WILLOW. Those things are encouraging, the qualitative commentary from physicians, but the data will ultimately control as we all know and understand. I think at this point, the simple and most honest, answer is we need to just unblind the data and see what we have. I don’t know, Bryan, if you want to add anything specifically about the question, just in light of the last one.
Jennifer Kim: No problem. Okay, thanks. And if I could ask a question on TPIP maybe for Gene, I wanted to confirm is Phase 3 advancement in PH-ILD still contingent on getting PAH top-line data, maybe to get a better sense of powering and I know that the intervals are wide, but can you say what the six-minute walk change was in placebo and PH-ILD and what the baselines were for both arms?
Eugene Sullivan: So the question is about Phase 3 and moving forward into Phase 3 I think that will be primarily based upon the results of this trial as we analyze these results and the ones that will come in subsequently and also on the experience of Tyvaso in this population. I think it’s harder to extrapolate on data on efficacy and data on a lot of things from a PAH. population to PH-ILD. It’s such a different disease process that I don’t think we’re going to be looking at the PH data to inform key aspects of a design of a Phase 3 trial for PH-ILD. And I think your second question had to do with the six-minute walk test. We’ve given the delta right, that 30 meters placebo controlled. And so you were you asking what was the actual change from baseline in the group and the treatment groups?
I was asking what the placebo six-minute walk change once I think you’ve given the placebo adjusted change and then after the placebo change and then also what the baselines were for both arms. So I’ll just say broadly that probably the best way to do it is placebo-controlled. That would be the primary analysis. In general, it had to do it — what we saw in the primary analysis was that there was a decline among placebo patients and a stability among active treatment patients. So that general pattern was what it resulted in. It’s on the 30-meter delta between the two.
Operator: Your next question comes from Stephen Willey from Stifel.
Stephen Willey: Yes, good morning. Thanks for squeezing me in. Just a quick ASPEN question. So on the the manuscript detailing patient baselines suggests that there were about 20% of patients with elevated eosinophils. Curious as to whether or not you said anything about eosinophilic levels as it pertains to WILLOW and then just kind of curious as to your thoughts around the impact of brands. So in this elevated eosinophilic population where it may be inflammation, maybe not so neutrophilic image. Thanks.
William Lewis: Yeah, the short answer is I don’t know the answer to that question, Steve. I can ask Gene, if you know offhand otherwise or Bryan, if someone else wants to comment otherwise we’ll have to get back to you.
