Day, and thank you for standing by. Welcome to the Arcutis Biotherapeutics Atopic Dermatitis updates call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising that your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker, and that's Eric, Head of Investor Relations. Eric McIntyre, you may begin.
Thank you, Tanya, and good morning, everyone, and thank you for joining our call this morning on the exciting data we've released recently across our atopic dermatitis program. The slides for today are available on the investor section of our website. On the call this morning, we have Frank Watanabe, President and CEO, and Patrick Burnett, Chief Medical Officer, and we're also joined by Dr. Larry Eichenfield, Chief of Pediatric and Adolescent Dermatology at Rady Children's Hospital, and Professor of Dermatology and Pediatrics at UC San Diego School of Medicine. I'd remind everyone quickly that we will be making forward-looking statements during this call, and any of these statements are subject to certain risks and uncertainties. With that, I'll hand the call over to Frank.
Thanks, Eric, and let me just start out by thanking Dr. Eichenfield for joining us as well. For those of you who don't know him, he's probably, you know, one of the world's leading authorities on atopic dermatitis, so, we felt it would be really valuable to have his, perspective and commentary on the data, that we're going to walk through with you. I'm on, on slide 5 of the slide deck now. Before we jump into the detailed presentation of the data, I just want to hit a couple of high points. You know, I think one of the themes in our discussions with, investors this year has been that 2023 has really been a year of execution for, for Arcutis, and that continues to be the case with, with some of the recent AD developments.
You know, obviously, first and foremost, the launch of ZORYVE in plaque psoriasis is our top priority, and that continues to strengthen in performance. We're continuing to get very, very positive feedback from clinicians out in the field and patients, and continue to also make steady progress on our coverage wins, as we talked about, on the Q3 earnings call. This latest data set that we released this morning is the fifth successful phase III study that we've completed in the last 18 months. I think for a small company like us, or for any company, frankly, that's a pretty impressive track record and credit to Patrick and his team for their outstanding execution around the clinical studies.
We just recently submitted a supplemental NDA to the FDA for roflumilast cream for atopic dermatitis in children 6 and above, and adults, and that sets us up for a second launch in 2024. So you know, we continue to expect approval of our foam and seborrheic dermatitis in mid-December, which you know, would translate into a launch early Q1, and then the supplemental NDA for AD sets us up for a launch of the new concentration of the cream, probably you know, sometime in Q3. And you know, when you take this all together, along with the soon-to-be-filed scalp psoriasis indication, that's 4 different indications in 3 different concentrations, 2 different formulations, all wrapped around the topical roflumilast, and targeting about a 13 million patient total addressable market.
We think it's a very, very large and exciting opportunity. On slide six, I'll just remind you very quickly of the Arcutis pipeline, and especially the yellow and orange bars at the top continue to march along steadily. You know, we do also continue to be very excited about ARQ-255, our topical JAK inhibitor for alopecia areata, which is in the clinic. ARQ-234, which is our biologic for atopic dermatitis, that we continue to progress to the clinic, and then some of our other programs like ARQ-252 and some of the other programs that we've talked about earlier.
On slide seven, just to talk a little bit more about the opportunity, you know, we've focused in the past on some of these other markets, but I'm focusing specifically on atopic dermatitis in the middle. Very, very large prevalence. You know, over 25 million Americans are estimated to have atopic dermatitis. And I think probably most notably, if you look at patients in a doctor's office receiving topical treatment, you know, there's over 2.5 million patients with mild to moderate AD receiving topical treatment from a dermatologist. And you know, those are all patients readily addressed by our existing commercial infrastructure. And then about 4 million patients being treated outside of dermatology in primarily primary care and pediatric settings.
As we said before, we are very interested in addressing that 4 million group of patients outside of the dermatology office, but we intend to do that through some type of partnership rather than building our own infrastructure. As you look at the slide, you can see, you know, more than 6 million, almost 7 million patients that we're targeting in the dermatologist's office, and then about another 6 million patients outside of the dermatologist's office across the various roflumilast indications. Finally, on slide eight, just to update you in terms of regulatory progress. Oh, Patrick? Oh, yeah, okay. I'm sorry. I thought maybe I'd stolen one of your slides.
As I mentioned, we've submitted the sNDA for the 0.15% cream in ages 6 and above, and we expect a 10-month review, so that tees us up for expected approval around Q3 of 2024. We would anticipate filing another supplemental NDA for the younger kids, the ages 2 to 5, based on the data we're going to review with you all today, sometime after the approval in the 6 and above. With that, I'm going to turn things over to Patrick to get to the exciting stuff, the data.
Great. Thanks, Frank. The data that we released today from INTEGUMENT-PED represents the fourth data set for atopic dermatitis. If you keep in mind that we released previously INTEGUMENT-1 and INTEGUMENT-2, and that covered ages 6 and above in AD, we also recently read out the long-term data for that age group from INTEGUMENT-OLE, our open-label extension. We understand, well, the profile of AD, and I think that you'll see that the data today for our 2- to 5-year-olds from INTEGUMENT-PED is highly consistent with these previous data. We summarize that now on slide 10. Here we show the profile for atopic dermatitis. On the efficacy side, we're showing that we are getting improvement as early as 1 week.
Again, this is consistent across our previous studies, as well as a rapid improvement in itch as early as 24 hours after application was demonstrated in INTEGUMENT-1 and INTEGUMENT-2. Turning to safety and tolerability, this is an area of strength historically for us. You know, this is our fourth indication that we've studied, but it's especially important in atopic dermatitis due to the high prevalence in children, and here specifically, we're studying 2- to 5-year-olds. Importantly, our formulation doesn't disrupt the skin barrier. That's one of the foundational and pathophysiological considerations for atopic dermatitis, and it doesn't include any sensitizing or irritating ingredients, and it can be used anywhere on the body.
I mentioned from the INTEGUMENT-OLE study that we now have long-term treatment data, and I really see this as kind of the necessary bookend for our phase III studies like INTEGUMENT-PED. In our INTEGUMENT-PED and INTEGUMENT-1 and -2 studies, we showed an early onset of efficacy, but what's really important also is that you're able to maintain that over the long term. I think you'll see, because we're gonna cover those OLE data today, that we not only are able to maintain, but in fact get a continued increase after the initial four-week period when patients roll over. We also used an innovative study design, where we looked at maintenance dosing. This was applied proactively to those areas that were already clear in order to maintain disease control in these patients.
Now, the efficacy and safety has been consistent across ages. We saw this in INTEGUMENT-1 and INTEGUMENT-2, which included 6- to 11-year-olds as well as adolescents, and now we're showing the INTEGUMENT-PED data in ages 2-5. With that, I'll transition to slide 11 and talk about the study design. This was an active versus vehicle phase III trial with 4 weeks of dosing. The dose that we used in ages 2-5 was 0.05%, so that's different from the 0.15% that was in INTEGUMENT-1 and INTEGUMENT-2. Subjects were randomized 2:1, and we had 652 subjects in this trial that were randomized. Now, the eligibility criteria for a study like this are really critical.
We enrolled mild or moderate patients, so that's on the Validated IGA, a 2 or a 3. Validated IGA is also gonna be our primary endpoint, so I just wanna explain a little bit that that's a 5-point scale going from clear, a 0, to almost clear, a 1, and then mild, moderate, and severe being a 2, a 3, and a 4. So we're enrolling patients who are mild or moderate. Obviously, the ages we've already covered. Importantly, we allowed a BSA of greater than or equal to 3, but we didn't cap the BSA. And this is because in atopic dermatitis, it's quite common for patients to have quite extensive disease, and this is particularly true in these pediatric populations. So these patients all had to be mild to moderate in the severity of their AD, but we didn't cap the body surface area.
Our primary, I mentioned, is validated IGA, atopic dermatitis success at week 4, and then you can see the secondary endpoints all listed out, on slide 11, and those include some endpoints at weeks 1, 2, as well as week 4. Turning to slide 12, you can see the baseline characteristics for this trial. We had about three-quarters of the patients were moderate that were enrolled. And coming back to this, to the percent BSA, you can see that the BSA is quite high enrolled into this trial. Overall, it was about 22%. That means that the body surface area that was covered with disease in these patients was approaching a quarter on average, and the median was 17.
Now, comparing this to INTEGUMENT-1 and INTEGUMENT-2, the mean body surface area in those studies was 13.6, and the median was 10. So this is reflecting a difference in the pediatric patient population with regard to their disease as they're entering into the trial. You can see as well that over three-quarters of the patients had sufficient itch in order to be considered for the analysis of the worst itch numeric rating scale. That means that they had to have an itch of 4 or greater on a 10-point scale. Now, keep in mind that these are 2- to 5-year-olds, so we're capturing that itch through the parents and asking the parents to assess the itch that they observed in their children.
That is a difference between this study and the adults and adolescents and older children that were assessed in INTEGUMENT-1 and INTEGUMENT-2. Coming on to the primary endpoint now on slide 13, you can see that we achieved statistical significance. In fact, if I can just cover this right now, we made statistical significance, not just in this primary endpoint, which is validated IGA at week 4, but in every single secondary endpoint as well. We anticipate releasing these data into an abstract or a presentation at some point in the future, but we're just covering some of the key data points here. For the primary endpoint, over 25% of patients got to validated IGA success. That means they got to clear or almost clear and had a two-point improvement.
So that means that any of those patients who came in at mild, in order to meet that two-point improvement, they had to get all the way to clear, which means that they had zero, absolutely no disease on their skin. We also separated very nicely already at week 1, at 9% versus, less than 1% for vehicle, and that was also statistically significant, and then had a big bump in efficacy up to 21% by week 2. So these results are very consistent with the efficacy that we saw with INTEGUMENT-1 and INTEGUMENT-2, with an early onset, already at week 1, and then continuing to improve all the way through week 4.
For INTEGUMENT-1 and INTEGUMENT-2, the numbers were numerically a little bit higher at 29 and 32 for INTEGUMENT-1 and 2, and I think this really reflects the differences in the amount of body surface area that patients had, varying between these trials based on age. Now coming on to EASI-75 on Slide 14. This is an endpoint that we have focused on primarily in our atopic dermatitis releases because of the clinical relevance of EASI-75. So this endpoint is taken with a different methodology from IGA and actually incorporates body surface area into the assessments for each of the regions, as well as the different signs of the disease, such as erythema, scaling, lichenification, and so forth.
Here we had approximately 40%, 39.4% of patients reaching EASI-75 success—or sorry, EASI-75 endpoint at week 4. EASI-75 takes that baseline EASI score, and in order to be considered a responder on this binary endpoint, you have to have 75% of your disease improved at the time being assessed. Here for week 4, it was 39.4% versus just over 20% for vehicle. Very good separation. Coming on to the earliest time point that we have at week 1, we're already at 19% of patients reaching that response criteria, and that's compared to vehicle. That's actually a faster, a faster improvement than what we saw in INTEGUMENT-1 and INTEGUMENT-2.
These numbers are very similar to what we saw in those earlier studies. So 42.7 was the pooled data for INTEGUMENT-1 and INTEGUMENT-2 for week 4, and this is versus 39.4. So we saw a really good maintenance, maintenance of the delta between active and vehicle, as well. So we see these results as very consistent with what we saw in our previous studies. Transitioning to Slide 15 and looking at the itch response. Again, itch is assessed by parents. Nevertheless, we saw again nice consistency here with 35.3% of patients reaching a WI-NRS response, which meant that they had at least a 4-point response from baseline.
And this included all the population who had a four or greater at baseline, and a rapid response shown by the almost 15% of patients who responded already after just one week. Now, in the future, we will be able to talk about how quickly this came on because these data were captured with a diary. We showed those for INTEGUMENT-1 and INTEGUMENT-2, that response in INTEGUMENT-1 and INTEGUMENT-2 was as early as 24 hours after initiation. So look forward to those being presented at a future time point for INTEGUMENT-PED as well. Now, on Slide 16, we start to look at the safety that was observed in this trial. And here I really want to focus on the subjects discontinued due to an adverse event.
We have numerically similar results between roflumilast and vehicle, with 1.1 for roflumilast and slightly higher at 1.9% for vehicle. That difference for vehicle reflects primarily worsening of atopic dermatitis. Two of those four subjects who discontinued due to an adverse event in vehicle were because of their atopic dermatitis worsening. So completely expected results there, and a very high completion rate was observed in this study. We didn't have any subjects discontinued for nausea, vomiting, or diarrhea, which are kind of typical PDE4-related adverse events. And in fact, on Slide 17, showing all of those adverse events that occurred in greater than 2% of subjects in any group.
Here you can see our top two were typical things that you would see in pediatric patients, upper respiratory tract infections and pyrexia, which is fever. It's not till you get down to diarrhea and vomiting, which are both less than 3%, in this study, and both of those are kind of expected PDE4-related adverse events. And in fact, if you go all the way to the bottom, you see that atopic dermatitis, which represents a worsening of the disease, is more common in vehicle than it was in active, exactly as you would expect. For dermatology, it's always good to show a couple of pictures. So on Slide 18 and 19, we're showing here a three-year-old male. He identified as Hispanic for ethnicity and had quite extensive body surface area.
So kind of consistent with what we had in this trial, this young man had that 39% body surface area and an EASI score of 25, which is quite high and in that range where, you know, depending on age, he would be eligible already for a biologic. This is a patient who went from a baseline IGA of 3, that is a moderate patient, and by week one, was already a 1, which is almost clear, and then maintained that through week four. So this is a responder. I think it's good to see pictures because you can see just how extensive disease is at baseline, but also, that, you know, a patient who gets to almost clear really has very, very little disease.
So, this is one of the aspects of the IGA that's really important to understand, is that clear or almost clear, the difference between that can be just a, you know, a couple papules of disease in order for a patient to go from clear to almost clear. So I'm going to now talk about our open label extension results, and I really want to make it clear that now we're shifting to ages 6 and above. So our INTEGUMENT-OLE study did enroll 2- to 5-year-old subjects, but we don't have those data yet. Those patients are still in this trial, and we'll read them out at a later time. Because our INTEGUMENT-1 and INTEGUMENT-2 trials wrapped up earlier in the year, those subjects were able to complete their full 52 weeks of treatment.
And so we have an interim analysis that focuses on these ages 6 and above. We call it an interim analysis because the study is still open with 2- to 5-year-olds in it... But these are the complete data for these ages 6 and above subjects. On slide 21, you can see a diagram that kind of gives you an understanding of them. All these subjects completed INTEGUMENT-1 or INTEGUMENT-2. We had 658 in the trial. And you can see that they're split between two different cohorts, a 24-week cohort and a 52-week cohort. And that's important because you will see that there was a drop-off in the number of subjects that went out to 52 weeks, and that's kind of by design.
You can see that, that not all of the subjects were enrolled into that 52-week cohort. So I just don't want anybody reading into that too much about an artificial dropout rate. That was actually part of how the subjects were enrolled. Now, in this open label extension trial, everybody was treated with the 0.15% dose, and again, it's 0.15 because this is ages 6 and above, and the primary endpoints were efficacy, but we also looked at—I'm sorry, primary endpoint was safety, but we also looked at efficacy endpoints as well. So going to slide 22, we'll cover safety first because this is an open label safety study. And what you see is that even over 52 weeks of treatment, the discontinuation due to an adverse event was only 3.2%.
So this is very low for a 52-week trial. If you look at the most common treatment-emergent adverse events, here again, it's greater than or equal to 2% overall because we only had a single arm in this trial. You see that what we're reporting here is COVID-19, upper respiratory tract infection, nasopharyngitis, and headache, nothing greater than 5%. So really, we don't even see the PDE4 adverse events that are commonly, that are the most common reported in our phase III trials. We're not seeing those in this open-label extension as one of the more common. These are the typical things that you would anticipate in patients. As you move on to slide 23, this looks at our efficacy over time by validated IGA atopic dermatitis.
This was the primary endpoint in our phase III trials, and here again, we're kind of following them out. Just to orient you on this, percent of patients is along the left, weeks in treatment along the bottom, from 0 to 56. It goes to 56 because patients are included for the first 4 weeks that they were in the pivotal trial, INTEGUMENT-1 or INTEGUMENT-2, and then they rolled over and received either 24 or 52 weeks of additional treatment. The period in the phase III study, as INTEGUMENT-1 and INTEGUMENT-2, is highlighted in yellow along the left. And then as they transition, we show the efficacy for this cohort of patients. This is—these numbers are slightly different from our overall efficacy because here we're looking at this cohort of patients that rolled over into the OLE.
How did they do at week 4? Then how did they do as we got to weeks 28 and 56? What you can see is that we are showing two arms, or I'm sorry, two different groups, and that's because your trajectory could be different based on whether you were on active or vehicle in the parent study, especially earlier in that trial. Even though after that yellow period is completed at week 4, from that point forward, everybody is on the 0.15% dose. So, they really aren't two arms. We're just tracking patients because of the coming from vehicle or active in the original study.
What you can see is that focusing on the active patients, 28.5, they get up to over 45% already at validated IGA success at week 28. That's 24 weeks after completing that trial. And then by week 56, which is the last time point, they're up over 50% of responders. So we're seeing a continued increase in efficacy over time. And I'm gonna talk a little bit also about our maintenance dosing at the end. So just keep in mind that these efficacy results are with patients actually, when they get to clear, decreasing the amount of time that they're using their drug. So this is really kind of a real, more real-world, study approach where patients can go, you know, on and off this maintenance dosing depending on how their response is.
Looking at slide 24, I mentioned previously that we really like to focus on EASI-75 because we think that this is a, a very relevant endpoint and it also incorporates body surface area. Starting, I mean, same orientation to this graph, starting at 42.6% of patients responding coming out of the pivotal trials, that number goes up to 61.5% and then, up to 66% by the time they get to, week 56 for those on active. You can see the patients that are on vehicle, after they roll over, kind of quickly get to exactly the same level of efficacy as their, cohorts who were on active four weeks earlier.
Again, really good maintenance, not just maintenance of efficacy, but also efficacy build over time, which we hadn't seen in any of our previous open label extensions for other indications. And I think really represents an aspect of atopic dermatitis that where patients getting under good control actually continue to see benefit over time. And as I move to my last slide on page 25, this looks at the maintenance dosing. So just to give you a little bit more understanding of what we mean by that. So we proactively treated patients when they got to clear, stopping the everyday dosing, the QD dosing, and instead switching to twice a week. And then patients were able to maintain on that twice-a-week dose for as long as they could.
They would switch back to daily dosing if one of two things happened: if they considered that their signs or symptoms were not adequately controlled. That is a very low bar. If the patient themselves is not happy with how they're doing, they go off twice-weekly dosing and go back to once-a-day dosing. If we step in and intervene, if they get to a validated IGA of mild, because that was the eligibility criteria to come into the trial. Even if patients think, "Oh, no, no, I'm totally fine," we still continue, we switch them over to once-a-day dosing if the investigator assesses them as mild when they come in for a visit. What we're able to show is that this maintenance dosing was able to keep two-thirds of patients...
to remain on maintenance dosing, twice weekly for over half of their time in the study, which meant that when patients went on to it, it was quite likely that they were going to remain on it for the kind of remainder of the study. So we're very happy with this, with this response. And we feel that it fits quite nicely with clinical practice, because this is how steroids are commonly used, and this is the feedback that we got from our atopic dermatitis advisors, including Larry Eichenfield. So with that, I'm going to turn it over to Larry to give some context on how he sees these results in both the INTEGUMENT-PED study as well as the open label extension.
Larry is uniquely positioned because he's both an investigator and really participating in every significant atopic dermatitis trial, that's conducted, but as well, a very active practitioner. So he's able to kind of translate these types of clinical results into real-world practice in a very unique way. So with that, I'll turn it over to you, Dr. Eichenfield.
Thank you, Patrick. Yeah, my job's really to put it in context, put the data into context, and I'll start with the big picture, which is, you saw the population data, but translate that to clinical practice. Well, I'll be seeing patients in a few hours, and there's a lot of atopic dermatitis, and there's a lot of atopic dermatitis in younger children. There's, you know, a desire for us to bring long-term control of the itch and the rash of atopic dermatitis to patients and their families, and to do this safely and effectively. Really, there's a clinical need to be able to do this without relying on traditional topical corticosteroids alone, because there's issues with them and concerns about them.
And certainly, no methodology that allows someone to use, chronic topical corticosteroids, daily topical steroids as a way to control more significant disease that needs more consistent anti-inflammatory therapy. So my look at the dataset in relationship to that is to say: How will this work in clinical practice? And first of all, start off with the INTEGUMENT-PED study, right, which is that, the data was very consistent with the INTEGUMENT-1 and INTEGUMENT-2, with the older children and adult results. The lower dose that was developed for these 2- to 5-year-olds is effective, safe, and appropriate. And probably the biggest takeaway, which is nerdy, but translate to clinical practice, it's very common in younger children to have relatively high body surface areas involvement.
You know, a 22% body surface area involvement in an adult is, you know, considered systemic therapy. It's just one of those, you know, you remember, psoriasis, 10% body surface area is in the severe category. Atopic dermatitis, you can have a higher body surface area in our older patients, but it's very common in the younger patients, and that's what you see. In interpreting these results, you know, 2/3 of the patients were moderate at baseline. It's very important to know there was no cap on BSA, and they ended up with this 22% body surface area, so a lot of atopic dermatitis to clear in the period of time.
Also remember that this, this drug, when we're looking at this data, this drug is being used once a day with a 4-week time course for evaluation. And, you know, we're not doing comparison analysis here, but that's a quick time point that's being looked at because it was thought when the studies were designed, that they'd be able to show their differential from vehicle within that time point, and I think that's, that's really important. And then the itch response is rapid and consistent. You know, even week 1, you see that efficacy, which is showing rapid onset of effectiveness. And I think the EASI-75 data in the INTEGUMENT-PED is a very relevant time point. It gives you a real sense of these patients who come in with mostly moderate disease, with pretty significant EASI score.
We don't necessarily do EASI scores in practice, but with a lot of body surface area and a lot of eczema, they get their improvement within that time course very effectively. Now, the other dataset, again, that six-year-old plus right now, the INTEGUMENT open label, is mind-bending or landscape-bending, and I'm really excited that the company elected to be willing to test in their open label extension rather than go through a traditional methodology of, okay, if you're clear, you stop it and go back and use it, and continue to use that drug as needed with disease flares, that they really tested this maintenance regimen with incredibly great results. Because we see safety and tolerability with chronic long-term treatment, and atopic dermatitis can require chronic long-term treatment very commonly across the landscape of ages.
It was very low discontinuation rate due to adverse events in the study. You showed the increasing efficacy over time, up to that, you know, up to 56 weeks, as measured by both the global score and that EASI-75. The concept of being able to say to a patient or a family, "You know, after you're clear, why don't you go twice a week for the next 6 weeks, 4 weeks, 8 weeks?"... you know, and show that, let's make sure we can continue to keep the patient clear with twice a week, rather than this sort of, wait till there's a flare and then treat in a medicine that's bringing, with it, good tolerance and safety, is something that could be a real shift in our, management. So the proactive maintenance approach is incredibly strong, data.
You know, both looking at the data in context, you know, consistency of roflumilast with the younger kids studies and the open label, really showing that increase in efficacy over time, capturing more of the population who makes it to EASI 75. That proactive maintenance, which I think is really important to help to allow us to direct our patients to use a medicine in a long-term regimen of care, in a way that they'll feel comfortable and can really help to control both the symptoms, the itch of atopic dermatitis, and to keep most of the patients clear.
Great. Thank you so much, Larry. I really appreciate the comments, and we are gonna transition now to Frank, to take question and answer, and I'm sure there'll be some questions for you. So, Frank?
Yeah. Thank you, also, Larry. That, that was very helpful. Yeah, so we're gonna open things up for Q&A, and operator, if you could help facilitate, or Eric, if you could help facilitate questions as they come in.
Certainly. Ladies and gentlemen, as a reminder to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please wait for our first question. Our first question will be coming from Seamus Fernandez of Guggenheim Partners. Your line is open.
Great. Thanks for the questions, and congratulations on the Integument-PED results and the OLE structure. Just a couple of questions. You know, historically, I think if we look back, and this is maybe a little bit of a history question for Dr. Eichenfield and also for the team. I just wanted to get a sense for where we saw some unique uptake of products like Elidel historically. My recollection is that it was that younger two to five patient population where we saw some pretty extraordinary uptake of those products because parents really want to avoid topical steroids pretty aggressively. Just hoping to better understand how you are thinking about that opportunity.
But my understanding is also it was very significant uptake among pediatricians in particular, maybe more so than dermatologists. So just interested to get your thoughts and feedback on that and the opportunity to broaden into different physician prescribing populations. And then, you know, separately, as we think about the OLE opportunity, is that a labeling opportunity for the team, or is that more of a marketing study? You know, such that you know, that can be promoted more from publications, things like that, just in terms of the promotional opportunity from the OLE study. Thanks.
Yeah, sure. Thanks, Seamus. Yeah, so Larry, you wanna maybe start off by addressing Seamus's question about sort of the history with the TCI or, yeah, the TCIs and where we saw-
Yeah
the most adoption, and then, Patrick, maybe you can address the other question.
Yeah. Well, I see the history question as being right on. There certainly when Elidel came out, there was a rapid uptake, especially in the younger kids, and it was true that that was amongst non-dermatologists as well as dermatologists, with the pediatric community being very happy for exactly the reasons that were stated. There's always been concerns about topical corticosteroids with younger kids in particular, where there's more body surface area and concern about absorption, and Elidel was sort of used very broadly. So the follow-up of that, do I think there's potential for it similarly to be brought to use? I think that, you know, there's a clinical need in that younger age group.
The data is, you know, very strong and brings the, you know, especially it's strong in the age group, but of course, it's also strong because of the consistency of roflumilast across the ages, study. So, I do think that it can-- if it can fit the bill for the patients, then the different practitioners, not just dermatologists, may look at its utility. And I do think that the design of the, and the discussion of the open label extension is really exciting and something that can bring a lot of interest from practitioners as well, and I'll defer to the team in terms of the question of whether they think that's a labeling opportunity or just a different aspect to differentiate it in the market.
Yeah, I can, I can handle that. So the study, the open label extension trial, INTEGUMENT-OLE, was designed as a safety study, and as such, we expect that it'll be described in the label. So if we're following the example of our open label extension for DERMIS-1 and DERMIS-2, that study was included in the label, in particular to comment on the safety over time. So then, you know, as the study gets described in the label, then there is an opportunity, depending on the promotion, for it to be promoted as consistent with label. So, we do see that as a study that will appear in the label, so we're quite excited about it.
Great. Maybe just as my final question or, and then I'll turn it over. As we think about the, you know, sort of promotional needs, can you just help us understand a little bit of, you know, where you think the reach is necessary? I think, Frank, one thing that you've talked about is an opportunity to actually separate the sort of promotional opportunity and that, you know, it might be possible to bring on a larger partner who has a presence, a strong presence in the pediatric and primary care market, such that the reach of, you know, the topical roflumilast can actually broaden.
Can you maybe just walk through a little bit of that opportunity as you see it, and when something like that would make the most sense, as a potential partnership?
Sure. Yeah, absolutely, Seamus. Yeah, I think I made reference to this earlier in my comments. You know, as we look at the marketplace today, almost half of the patients who are currently receiving treatment for either psoriasis, seb derm, or atopic dermatitis, and about two-thirds of atopic dermatitis patients are being treated in primary care or pediatrician's offices, or, you know, in some cases with AD, in allergist offices, although there aren't a huge number of allergists in the country.
You know, we intend to continue to promote roflumilast for its various indications in the dermatology office as Arcutis, but that we would be looking for a partner to help us promote that in primary care and pediatrics, and we'll have to sort out, you know, who takes allergy as we move forward. So you hit that exactly on the head. We just don't think that it's a good use of shareholder value for us to build a 500-person primary care sales team.
As you think about, you know, what that might look like, I, you know, I think our preferred, sort of structure is some sort of BD arrangement t where there's a, you know, it's a co-promote, but there's revenue sharing so that the partner has sufficient skin in the game, and, and, you know, we feel like that's the best alignment of, of the two companies', interests. In terms of timing, you know, what we've said, and we continue to believe, is that it's important to have this partnership sometime around the atopic dermatitis approval in Q3. And I emphasize around, because I think that, a, the, the primary care community and the pediatric community are going to be looking to dermatologists to, for cues about the adoption of any new topical therapy.
The first and most important thing is for us to win with the dermatologists, and that'll be our focus right out of the gate. You know, if in the first month or two, we don't have that primary care partnership in place, it's probably not the end of the world as we're getting trial in dermatology. Certainly, very quickly, we would want to have that primary care partnership in place so that we could drive uptake in the other specialties as well.
Thank you.
One moment for our next question. Our next question will be coming from Louise Chen of Cantor. Your line's open.
Hi. Thanks for taking my questions, and congratulations on all the great data. I wanna just follow up and ask you on this partnership that you were discussing here. You know, have you identified certain candidates that are ideal for you, and would they also be interested in European rights? I also wanted to ask you on spending, how much incremental spend do you need to launch AD, if everything's approved as anticipated, and, you know, how do you feel about the resource to launch both AD and also psoriasis? Last question is just on the uptake of AD versus psoriasis. How do you compare and contrast those two types of launches? Thank you.
Yeah. Hey, Louise, great to hear from you. In terms of potential candidates, you know, there's a finite number of companies that have existing primary care presences, and, you know, some of them do and some of them don't call on pediatricians. Yeah, we've mapped out the landscape, and we know who are potentially partners for us. You know, we don't have a deal done yet, so we'll have to see who it ends up being at the end of the day. In terms of European rights, that's hard to say. I think that's something that will come in the context of any discussions.
But, you know, certainly many of the companies that have large primary care footprints in the United States are multinational companies that do have European presence, and so that certainly might be a factor in as well. In terms of the resourcing question, you know, there certainly will be some incremental marketing spend associated with the atopic dermatitis launch. Probably the most notable incremental expenses that we have communicated previously, we anticipate a modest sales force expansion associated with atopic dermatitis approval. You know, we will, at that point, have topical roflumilast or ZORYVE for plaque psoriasis, topical roflumilast foam for seborrheic dermatitis, we'll have just launched, and then we'll be launching yet a third indication in short order.
You know, I think there's just a finite capacity for a sales rep to optimally promote a number of products. I think three launches in short order is probably exceeding that. So we believe that expanding the sales force is the right thing to do in terms of driving the shareholder value. Then with regard to your question about uptake, you know, I think Larry touched on this, too, but my sense is that the uptake in atopic dermatitis may be somewhat faster than in psoriasis. And that's primarily because of some of the dynamics that Larry touched on, that you know, parents are very motivated to get away from topical steroids, and I think there's also some lingering concerns in the parent community around topical calcineurin inhibitors.
And so, you know, to have a really good, safe, non-steroidal that can be used chronically and used everywhere, I think there will be a big push, especially from the parent community, to adopt this therapy and to switch their kids over. So we would expect to see, I think, somewhat faster uptake in the atopic dermatitis realm than we've seen in psoriasis.
Thank you. One moment for our next question. Our next question will come from Chris Shibutani of Goldman Sachs. Your line is open.
Hey, this is Stephen on for Chris. Thanks for taking our questions. I had one for Dr. Eichenfield. Just curious if you see roflumilast cream, particularly in the atopic derm setting, being used as a monotherapy or potentially in combination with other topicals or even biologics. And then for the Arcutis team, just curious what kind of utilization management you might expect for the cream in atopic derm, and if we should expect this to be similar to what's kind of played out for the plaque psoriasis indication. Thank you.
Yeah, so,
Yeah, so the-
Go ahead.
Yeah. Happy to take that on. You know, I spent a lot of my time when I'm lecturing to dermatologists and occasionally pediatricians, saying that, you know, part of our job is to figure out from the clinical studies, which are monotherapy against vehicle, how things fit into real life with regimens of care. And I do think that this drug has the ability to be used as a monotherapy, but also very much used in regimens of care. You know, someone may get someone under control acutely with topical corticosteroids for a week and then shift over to this as maintenance therapy. In clinical practice, we're always trying to get a sense of, does someone have persistent disease?
It is a disease that comes under quick control, and then they go weeks at a time or months at a time or days at a time before they have active signs or symptoms of the disease again. So this has versatility. It can certainly be used as a monotherapy, but it also has the versatility because it can be used as in a you know clinical response for flared eczema or as in the open label extension in regimens that can you know sort of proactively treat the disease to minimize the rash and symptoms.
Yeah, and then, with regard to the access question, you know, certainly that's something that we will need to discuss with, with payers as we get this approval. But, you know, particularly with our pricing and access strategy, we, we have not seen a lot of utilization management, for, ZORYVE in plaque psoriasis, and we wouldn't expect it to be, substantially more draconian, in, in the atopic dermatitis space either. You know, given the prevalence of topical steroids as- that Larry just made reference to, I think, you know, it wouldn't surprise me if there was a step through, a generic steroid to get to, to, ZORYVE or to topical roflumilast for atopic dermatitis, but I, I wouldn't expect anything dramatically different than what we've seen in psoriasis.
Okay, great. Thank you very much.
One moment for our next question. Our next question will come from Tyler Van Buren of TD Cowen. Your line is open.
Hi, good morning. This is Tara on for Tyler. I was wondering if the responses were consistent across in children across the spectrum of body surface area. I know you showed the case study of the patient with the 39% BSA, but you know, curious to know about the child with 82% body surface area coverage. Given the increased concerns over using steroids in this population, would you expect this younger population to be easier to penetrate with a safe and well-tolerated and targeted product like ZORYVE, considering the higher BSA?
Yeah, Patrick?
Yeah, that analysis that you're asking about with regard to response across both severity and body surface area are data points that we will do. So we'll have those data, and we'll bring them out. Historically, what we saw with INTEGUMENT-1 and INTEGUMENT-2 was that we saw consistent results regardless of their incoming body surface area. So there's always some variation, but historically, we've seen a really good maintenance of that efficacy regardless of that. So we will be forthcoming with those data. This is just kind of the top line data.
As I mentioned in the presentation, we are gonna come back and talk about this at an upcoming congress, and we'll have more data kind of coming out over time, and we'll include that. With regard to the younger patients and the penetration and higher body surface area, you know, we took the decision to use the 0.05% dose in this 2- to 5-year-old patient population, really coming out of the phase II study that we conducted, where we saw very similar safety and efficacy in 0.05% and 0.15%. You know, there was just a little bit of an efficacy edge on the 0.15% dose, so we took that into the age of 6 and above.
But just again, kind of anticipating the population that we actually ended up enrolling into this study, where we expected to have higher body surface areas, and we wanted to make sure that we really kind of maintained our safety profile. And we didn't really see a fall-off as in efficacy as being a risk because of the consistency that we'd seen in that earlier small phase II study. We really see this as a validation of our dose selection. Now, these kids have very high body surface areas, but the safety and if you think about our data across all of the... You know, I think Frank said we released 5 successful pivotal phase III trials in the last 18 months.
If you look across that, the safety that we track is a very low percentage of patients who have a little bit of a like kind of first blush of a PDE4 profile. So, you know, in DERMIS, that was diarrhea. We saw some nausea and vomiting at very low rates, you know, always less than 3% in INTEGUMENT-1 and 2. We wanted to make sure that we get the same safety profile as we move down into these younger age groups with the high body surface areas, and that's exactly what we saw.
So we really see this as a validation of our kind of dose selection, because we have the same efficacy and we have the same safety and tolerability despite, you know, a shift in the demographics of the patients.
Patrick, if I can make one comment. You know, it's really important to recognize that when they chose the population here, that the study set up with no cap on body surface area. And that's different to some of our other drugs, where we're restricted in the percent of body surface area. Happened to be that, right, the mean was pretty high, right? It's the size of a kid's hand is 1%, so when you're, you know, 20% body surface area, it's a lot. But to be truthful, from translation to patients, if I have a patient come in and they only have, let's say they have 5% body surface area, the family still wants to know what's safe and effective, and they still might desire...
It's not like families say, "Oh, we only have 4% body surface area. We'll use topical steroids and not worry about it." We may discuss that they don't need to worry about it, but they still might be very happy with a non-steroid option that's gonna be effective and, you know, has the good safety associated with it.
Thanks, Larry.
One moment for our next question. Our next question will come from Vikram Purohit of Morgan Stanley. Your line is open.
Hi, good morning. This is Gospel on for Vikram. We have two questions. The first one is, how would you size the commercial opportunity for patients age two to five versus patient age six plus? And then, how many tubes would you expect the pediatric population to walk through annually, and which areas of the body do you expect the cream to be used for most heavily in this population?
Sure. So, thanks for the question. Let me address a couple of those, and I'm gonna call a friend here and ask Larry and Patrick to respond as well from a clinical standpoint. But, so in terms of tube utilization, you know, looking at the data across different products, we think that atopic dermatitis patients in general are probably going to consume something like four tubes a year. And that's really a reflection of the higher body surface areas that are associated with this disease. With younger kids, as you get very small, you know, their consumption will probably go down because you know, their body surface area is just less, so they need less drug, right?
And then in terms of the opportunity, in the dermatology practice, you know, the 2.6 million patients in dermatology, about 90% of those patients are ages 6 and above. About 10% are under the age of 6. That shifts as you go out into the primary care and especially the pediatric population. And you know, off the top of my head, I don't know if Larry or Patrick you recall, about 40% of atopic dermatitis patients are under the age of 18, but I don't remember the split across all specialties of 6 and above and 5 and below. But if one of our dermatologists recall, maybe you can answer that. And then Patrick, Larry, maybe you can also address that last clinical question.
Yeah, Larry, do you wanna maybe talk about where in this patient population of 2-5-year-olds, like, you know, where the most common areas for presentation would be in your, in your practice?
Yes. It's or I, I'll take it as, like, you know, what part of the body surface area will people treat with this? And the answer is any. One of the big issues we haven't mentioned, the general concern that we have amongst our doctors and other healthcare practitioners about topical steroids on the face because of skin thinning that can be seen in thinner skin surfaces. That's one of the major advantages of having a very well-formulated non-steroid that has, you know, is very tolerable. So I do think that this could be used pretty much anywhere, but people are gonna be very excited about using this for facial areas, thinner skin areas, body folds, because they are more vulnerable to having skin thinning with topical corticosteroids.
That may drive, drive use and, you know, sort of put it, you know, see how much they'll use it, depending upon the total body surface area involved.
Thank you very much.
I'm showing no further questions. I would now like to hand the call back to Frank for closing remarks.
Okay. Well, let me just thank all of our participants for calling in this morning. We felt like it was really important, given the amount of data that we've released just recently in atopic dermatitis to get you all together to go through it. And I think, you know, having Larry on the call was, from my perspective, invaluable. He's a trusted advisor and someone that we value his opinion greatly as the dermatology community does. So I wanna thank him again as well for his participation. And with that, we'll wrap things up. Thank you.
This concludes today's conference call. Thank you for participating. You may now disconnect.