Greetings, welcome to the ruxolitinib cream phase III data in atopic dermatitis webcast. At this time, all participants are in listen only mode. A question- and- answer session will follow the formal presentation. If anyone should require operator assistance, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It's now my pleasure to introduce Head of Investor Relations, Mike Booth. Please go ahead, Mike.
Thank you, Kevin. Good morning and welcome to our conference call and webcast to discuss atopic dermatitis, the disease, the medical need, and the phase III ruxolitinib cream data presented yesterday at the Revolutionizing Atopic Dermatitis Virtual Symposium. The slides used in today's webcast and those presented yesterday are available for download on the Investor section of incyte.com. I'm joined on the call today by Hervé and by Jim Li, our Head of Inflammation and Autoimmunity Development. We're also delighted to welcome Dr. Larry Eichenfield from the University of California San Diego. Dr. Eichenfield is a world-renowned expert in atopic dermatitis. He is Professor of Dermatology and Pediatrics, Vice Chair of the Department of Dermatology, and Chief of Pediatric and Adolescent Dermatology at UC San Diego School of Medicine and Rady Children's Hospital San Diego.
Given the global COVID-19 pandemic, Hervé will begin the call today with a few opening remarks on business continuity and how Incyte is reacting to the current environment. Dr. Eichenfield will provide us with some important context on the disease of atopic dermatitis and the evident unmet medical need before Jim shares data from the ruxolitinib cream phase III TRuE-AD program. We will open up for your questions. During the question- and- answer session, I ask that you limit yourself to one question and if needed, one follow-up, as this will enable as many of you to ask questions as time allows. I will also ask that we seek to split the Q&A session. First asking questions related to atopic dermatitis, towards the end of the hour, transitioning to any COVID-19 topics you might wish to raise.
Steven and Christiana will join us for the full Q&A session. Before we begin, I must remind you that safe harbor rules govern our remarks today and any forward-looking statements that we may make. I therefore encourage you to review the risk factors detailed in Incyte's SEC filings, included in our Form 10-K for the year ended December 31st, 2019. In addition, I would like to caution everyone that the COVID-19 pandemic is an evolving situation, and it is still relatively early to be able to assess the full effects of governmental, business, and social actions, and policies and overall economic conditions on our business. Accordingly, it's important to keep in mind that our statements on this webcast speak as of today. We'll now begin the call with Hervé.
Thank you, Mike, good morning, everyone. Thank you all for joining today's call. Before getting started, I would like to briefly address the ongoing COVID-19 pandemic. It's an unprecedented and very challenging time for people around the world, and our thoughts are with all of those impacted by the virus. I also want to thank our partners, our customers, and all Incyte associates who are working hard to ensure that all of our patients continue to receive their medicine. In terms of our business to date, we have not seen an impact on patients on Jakafi and Epclusa or on our supply chain and manufacturing processes. In term of regulatory process, the three products that are currently under regulatory review at the FDA continue to move forward as expected, as does our plan for the NDA submission of ruxolitinib cream before the end of 2020.
That submission will include the primary and secondary endpoint data that we are sharing with you today, as well as long-term safety follow-up, which is currently being collected. In terms of clinical development, we will continue to act in the best interest of patients, and we believe that keeping our clinical trial programs open and deferring enrollment decisions to study investigators and patient healthcare providers is most beneficial to patients. That said, we anticipate that short-term effects may begin to emerge across different aspects of our clinical program. For example, while we expect ongoing monitoring of already enrolled patients to continue, new patient recruitment in certain clinical studies may be impacted. We also expect the conduct of clinical trials may vary by disease state and by severity of disease, as well as by geography, as some regions are more adversely impacted.
We are monitoring the situation closely and actively preparing and implementing contingency plans across our global study, such as sending drugs direct to patients and adopting novel remote and telemonitoring tools as we seek to ensure continuity of care and data integrity for all participants in our studies around the world. Finally, last week we announced that Incyte and Novartis are working together with the FDA to launch a global phase III trial to evaluate the safety and efficacy of ruxolitinib to treat the cytokine storm associated with severe COVID-19. In these very sick patients, a hyperinflammatory response in the lungs can lead to respiratory distress and the need for mechanical ventilation.
We have both anecdotal clinical evidence and a strong preclinical rationale that JAK inhibition may have significant utility here. We are also seeking to launch an emergency expanded access program for these patients in the U.S., and we can assure patients currently taking Jakafi for its approved indication, as well as those participating in clinical studies, that we have ample supply of ruxolitinib for all our plans. I will end my introduction with a reminder of our ruxolitinib cream development activities and the timeline for the expected NDA and subsequent FDA review in atopic dermatitis, as well as the ongoing phase III trials of ruxolitinib cream in vitiligo with data expected next year. It's now my pleasure to welcome Dr. Eichenfield to the call. Larry, please go ahead.
Good morning, everyone. Larry Eichenfield here. As you heard, I'm a dermatologist and pediatric dermatologist in San Diego. Wishes of health and safety for everyone around the country. We've converted a lot of our practice to tele-dermatology as we rev up our hospitals for changes in practice. I'm pleased to be a part of the presentation as Incyte rolls out some very great data that I think could be very helpful. I've had a longstanding interest in atopic dermatitis and take care of lots of patients across the ages with eczema. What I will be doing is going through the landscape of atopic dermatitis and clinical need, and then I'll be available for lots of questions on the disease state.
I'll be talking from a mixture of what I know to be this evolving field on eczema, but also translating, taking care of patients and families across the ages with atopic dermatitis. Just a short story, sort of my summary points. This is a high prevalence disease. It's 10%-20% in young children, 2%-10% of adults. It has variable course and severity with a subset of patients with a lot of active eczema with secondary impact of the disease. It has significant disease burden as well as comorbidities associated with it. Historically limited treatments beyond topical corticosteroids and still a high unmet need for long-term inflammatory disease control. What is atopic dermatitis? It's really, it's a type of eczema. The term eczema is a broader term, but it's the most common type of eczema that presents with its typical morphology and distribution.
It's an inflammatory skin disease with a chronic or persistent course, and it manifests as eczema, and I'll show you some more images of typical eczema that we see. It also relates to bacterial colonization and secondary infections. The disease impacts multiplied by its associations with allergies, which include food and environmental allergies, asthma, hay fever, as well as neuropsychiatric effects, which I'll mention in more detail. First of all, eczema is a worldwide issue. We know that the eczema rates, it used to be and in non-industrialized parts of the world, around 4%-5%, but they increased to 12%-15% in many westernized or industrialized countries. There is more data on persistent and/or adult-onset atopic dermatitis as well.
There's this whole experience in China, for instance, where they had rates of 4% or 5% now in the major cities, 12%-18% with a lot of adult-onset atopic dermatitis. The reason isn't necessarily known. It may be a mixture of changes in environment both avoidance of parasites or early stimulants that might affect the immune system development, as well as pollution and other factors. We have pretty good data sets now that have come out in the last 10 years on rates in teens and adults. The disease can persist, or you can get new onset disease in 5%-7% of adults in the U.S., and recent estimates have atopic dermatitis. I added this slide because it's important.
One of the takeaways that I want people to get is that there's a lot of atopic dermatitis that's mild or moderate, and then there's another set that's moderate to severe, and that moderate group probably splits in half. Whether it be adults or children, we have a lot of mild to moderate disease. Even though there's been a lot of excitement in the space of systemic therapies with biologics and some oral medications that have been approved and developed for more severe disease, it's still now and will still be in the next 10 years, that most atopic dermatitis is going to be managed with topical agents. Just goes along with the severity data of the population. A few images to make sure you get a sense of what we're talking about. There's this variable severity with eczema, but eczema has this inflammation in the skin.
Where you see redness in any of these photos, we know there's inflammation that's in that skin. There's, of course, also some degree of skin effect, and you can see both oozing and crusting, as well as scale that develops from it. There can be a lot of bleeding in more severe disease, pigmentary changes, color changes that happen from the disease as well. You can get, in more chronic cases, which are very common, we get what we call lichenification. You get thickening, as well as erosions. This inflammation in the skin creates these secondary changes, but a lot of this is tied to pruritus as well, because you can have dry skin that causes pruritus, inflammation that causes pruritus, and pruritus perpetuates this cycle.
Before we go through a quick discussion of pathogenesis, I wanted to discuss the secondary consequences of the disease in relationship to infections. It's very common. With atopic dermatitis, there's increased bacteria in the skin, predominantly Staph, so we can get what we call impetiginized atopic dermatitis, as well as increased rates of infections. Even cold sore herpes can cause something called eczema herpeticum. I evaluated two patients over the weekend with the teledermatology who were in the emergency room for possible eczema herpeticum. Secondary infection is a big consequence of the disease. The medical consequences of disease, there are chronic rashes, there's pruritus, or itch, which drives disease manifestations, and we're definitely looking for products that can help to control that itch. Infections, as mentioned.
A lot of secondary consequence of the disease is tied to sleep disturbance, because that clearly has an impact on quality of life, work performance, and is very much tied to pruritus. Then there's the set of what we call the non-atopic comorbidities. We're talking about atopic dermatitis, but there's a tradition of comorbidities that are also considered atopic or relatively allergic in nature. This includes asthma, hay fever, allergic rhinitis, conjunctivitis, food allergy, and then contact allergy, which fits into allergic contact dermatitis, also known as occupational dermatitis. These images, you see a patient with asthma. I threw some peanut butter up there, a common food allergen that can develop in patients with atopic dermatitis.
The bottom right showing allergic contact dermatitis, where you get localized reactions to chemicals or metals on the skin, and that's the sort of patch testing, those little white things that we do as we try to figure out what particular allergens may be instigators of breakouts in atopic dermatitis. The rate of allergic comorbidities is really quite high across the ages, whether it be infants, children, or adults with hay fever, allergic rhinitis, seen in almost 50% of adults in more moderate severe disease. It's at least a third of even younger individuals with hay fever, allergic rhinoconjunctivitis. Asthma, about 40% as well. Food allergies, while it can trigger a subset of atopic dermatitis, it generally develops after the onset of atopic dermatitis. These are things that are sort of secondary issues that bring up the importance of atopic dermatitis.
The other thing that we've recognized in the past decade is the mental health effects, neuropsychologic effects of atopic dermatitis. Very high rates of anxiety and depression with more severe disease, with one in five adults meeting diagnostic criteria for major depression. The literature on attention deficit hyperactivity, ADHD, and when the first paper came out, we were a little questioning. Maybe they were just fidgety kids. It was a JAMA paper, really superb. Although we were appropriately skeptical, the data's really strong now that there are higher rates. A lot probably ties to sleep disturbance and fatigue.
The way I put together a sense of the burden, if you start looking at nine o'clock on this circle diagram, we have atopic dermatitis with itchy rashes, signs, and symptoms of disease, which is tied to, then we'll work clockwise to the symptoms with pruritus and frequent intense itch. Sleep disturbance very much associated with those findings in the itch, both falling asleep problems, staying asleep problems, which has a huge impact on quality of life. Atopic comorbidities, as mentioned, other comorbidities, including mental health, bacterial, viral, and other risk factors of some immune diseases and potential cardiovascular impacts. Of course, the impact on quality of life, social functioning, life course, and school and work performance of affected individuals. Don't spend a lot of time on pathogenesis, but there is now a sort of a holistic sense of the pathogenesis of atopic dermatitis.
There's some children who were born with barrier dysfunction, which is a lifetime thing. If you look at adolescents and adults, it's there as well. Drier skin, more open skin allows the skin to be more sensitized, which sets up the immune reaction that gives you these overactive cytokine production in the skin, which manifests as the rash. You can see on this diagram that there are a set of mediators of the disease, especially Th2 modulators and a variety of cytokines that are the targets. We'll be discussing later on in the data set how JAK inhibition can disrupt the inflammation in atopic dermatitis, looking at IL-4, 5, and 13, 31. These are mediators of the inflammation and the itch in atopic dermatitis. What therapy clinical needs are there? First of all, we start off with atopic dermatitis.
Moisturizing is important because patients can have a dry skin tendency. Dryness also tends to increase the itch of atopic dermatitis. We have many different approaches, but this does not handle the inflammation of atopic dermatitis that we see in most of our patients. We generally need effective anti-inflammatory therapy that hopefully will be antipruritic as well. Traditional mainstays are topical corticosteroids. We have about 70 different topical corticosteroids. They range in potency. They're used for acute flare management and intermittently for maintenance management. There are significant concerns worldwide of phobias with topical corticosteroids, concerns because of steroid absorption, especially with higher potency agents, as well as local effects with skin atrophy, stretch marks, et cetera, that limit its use.
While we often try to have patients use topical corticosteroids and use them in regimens, there's a lot of concern, and they have to be managed so that we stay away from the side effect profile. Topical calcineurin inhibitors came out around 2000, 2001 as non-steroid topical agents, tacrolimus and pimecrolimus. They're officially listed as second-line therapy. They can be used intermittently, not continuously. As we know, they had concerns with labeling due to concerns about malignancy that were raised by the FDA. They're fair to good efficacy, not that strong. They are approved either to mild to moderate or moderate to severe atopic derm, depending upon which drug you look at, and definitely are limited by tolerance with stinging and burning, which can occur. The relatively new kid on the block is topical crisaborole, which is a topical PDE4 inhibitor, used BID. Safety looks good.
They recently had an expanded indication down to three months of age, but a lot of stinging and burning and, I'd say, limited efficacy. Not that strong an anti-inflammatory for eczema. Still in play. I think not the market that was expected in terms of use, but that's sort of where we're at with it. There's reasons for that. As systemic therapy being niched for moderate, severe atopic dermatitis. Traditionally, we use very few systemic agents in patients in the U.S. methotrexate was the most commonly used but was uncommonly used and not approved. We also use the cyclosporine, azathioprine, mycophenolate. Lots of toxicity associated with them. Systemic steroids are most commonly used for acute rescue therapy but not advised. dupilumab, now approved 12+ as the first systemic agent.
I'm sure you're well aware of the evolution of systemic agents in the market in relationship to this with both oral JAK inhibitors, specific IL-13 blockers, IL-31 blockers, and we could go in detail, but that's not really what we want to stress today because it's very important in clinical practice to understand that most eczema is mild to moderate, that topicals will still handle most disease. From a clinical perspective, there's a great need for more potent, well-tolerated non-steroid. If I could get a well-tolerated non-steroid agent that really more effectively controls inflammation and effectively decreases itch, that's something that would be very exciting to patients and to the patients who take care of them. I also think the market of atopic dermatitis is still relatively untouched.
There's still a lot of work getting patients back into the office and to understand that we're sort of revolutionizing therapy with new tools that'll allow us to establish more long-term disease control rather than just occasional flare control. I regularly see patients with lots of eczema on their skin and lots of the secondary consequences, and there's this is how we have an expectation that we can fix it and get it under control. With new agents such as what Incyte is producing, we'll have more ability to do that. I thank you for listening, and we'll have an opportunity for some questions. At this point, I will turn over the material to Jim Li, who can discuss the great results on the AD drug.
Great. Thank you, Larry. This is Jim Li. I lead the inflammation and autoimmunity group here at Incyte, and I have the pleasure of representing the phase III study results that were presented yesterday, if you could slide to the next slide, at the Revolutionizing Atopic Dermatitis Conference, the virtual meeting held yesterday, presented by Dr. Kim Papp, one of our lead investigators in the phase III study. If you go to the next slide, please. Yes. Before I present the data, just wanted to remind people of the scientific rationale and the previous clinical work that was done with rux cream in atopic dermatitis. As Dr. Eichenfield mentioned, in terms of the pathogenesis of atopic dermatitis, I think we've learned of some of the main culprits, specifically the Th2 cytokines as well as the IL-31, that really drive both the inflammation and the symptoms of this disease.
We've learned over the years that a lot of that is driven by the JAK-STAT pathway, specifically JAK1. We know that the cream, or ruxolitinib, excuse me, has the ability to block those inflammatory pathways. A few years ago, Incyte conducted a phase II study in atopic dermatitis, where they looked at a number of different concentrations dosed twice a day and once a day for eight weeks. Those results have been published in The Journal of Allergy and Clinical Immunology. Based on the results of those studies, Incyte conducted the two phase III studies that I'm going to share with you today. If you go to the next slide, please. It's the study schematic or the study design. We tested two concentrations, 0.75% and the 1.5% rux cream. In the first eight weeks of the study, we compared it to vehicle cream.
After week eight, which was the end of the vehicle control period, patients who were originally randomized to vehicle were re-randomized to either 0.75% cream or 1.5% cream. In the 44-week long-term extension portion of the study, patients were instructed to retreat when they had a flare. When they either saw new lesions or felt the itch that drove their disease, they were instructed to retreat and then treat until the itch went away or the lesions cleared. We'll have results from the long-term extension sometime later this year. Today, we're here to present the results from the vehicle control period. If you could go down to the next slide, and then one more. This summarizes the study endpoints that were looked at.
The primary efficacy variable was the proportion of patients achieving an IGA, so an Investigator Global Assessment score of 0 or 1 with a two-point grade improvement from baseline, or what we call IGA treatment success, or TS, at week eight. The secondary endpoints included the proportion of patients achieving at least a 75% improvement in their EASI score from baseline, EASI-75, the proportion of patients with at least a four-point grade improvement in the itch NRS score from baseline at week eight. The next slide summarizes the eligibility criteria. Essentially, the criteria was almost identical to the criteria used in the phase II study. The only change was the expansion of the age range. In the phase II study, adults were evaluated. In this study, we went down to age 12. Adolescents and adults.
In terms of their disease severity, it was mild or moderate, so IGA 2 or 3, and the baseline body surface area involvement ranged from 3%-20%. In terms of key exclusion criteria, these are very common criteria used in most atopic dermatitis studies. Let's move to the patient demographics summarized on the next slide. As you can see, the distribution of the demographics at baseline was very similar across treatment groups. As I mentioned, the study included adolescents and adults. We had about 80% of the patients were adults, the rest were adolescents. About 60% of the patients were female. In terms of race, about 70% were white, about 23% Black, and the remainder were others, and those others primarily were people of Asian descent.
In terms of where the studies were done, about 70% of the patients came from the U.S. and Canada, and the rest, 30%, came from Europe. On the next slide shows the clinical characteristics of the patients. Again, as you see, the distribution was similar across treatment groups. In terms of the clinical characteristics, in terms of the body surface area involvement at baseline, it was around 10%. In terms of the mean EASI score, we saw a mean EASI score of 8 across the groups. In terms of the baseline IGA score, about 75% of the patients were moderate, the rest were mild. In terms of the mean baseline itch score, it was 5 across treatment groups, and the proportion of patients who came in with an NRS score of at least four or greater was about 2/3.
In terms of the duration of disease, it's a population with longstanding duration. The median duration was around 16 years, about 38%-39% of the patients had facial involvement. This is important because there are a lot of topical treatments where you really can't use it on the face at all or for very long periods. The next slide summarizes the safety that we observed in the study. What we saw from a safety perspective was that rux cream was well-tolerated and was not associated with clinically significant application site reactions. Again, with a lot of topicals, you see high rates or modest rates of application site reactions, pain, itching, burning, and we didn't see that in either study.
In terms of the adverse events, all treatment related, treatment emergent adverse events were mild or moderate in severity. That was very good to see. We didn't see any adverse events that were suggestive of any systemic exposure. In terms of the specifics, we see the overall rates of adverse events was around 25%-30%. In terms of those adverse events that were felt to be treatment related, and again, a much lower percentage. In fact, if you see, it looks like the vehicle control treated patients had the highest rates. Specifically to those application site reactions, as you can see there, and again, you see that it looks like the vehicle treated patients had the highest rates of those application site reactions.
In terms of discontinuation, you'll see in the next slide before I go there, the discontinuation rate was fairly low. Actually, the number of patients who discontinued due to adverse events was also very low. Again, you see the highest number of discontinuations occurred in the vehicle arm. In terms of SAEs or serious adverse events, again, a very small number. None of them were believed to be treatment related. The next slide shows the disposition of the patients that were randomized in both of the studies. We had about 1,250 patients or subjects randomized. As I mentioned, the discontinuation rate was low, it was around 10%. As you can see in the boxes themselves, the majority of those patients withdrew for personal reasons or were lost to follow-up. We had about 90% of patients complete the studies.
Let's turn to the efficacy. On the next slide, this is the primary efficacy variable, the IGA treatment success. Significantly more patients treated with RUX cream demonstrated or achieved the primary endpoint, the IGATS, compared to vehicle. As you can see, there's a breakdown here between the two studies. On the left there is a TRuE-AD1. As you can see by week eight in the 1.5% RUX cream arm, about 54% of the patients achieve this endpoint, 50% in the 0.75% arm, and 15 in the vehicle. In the TRuE-AD2 study on the right, about 51% in the 1.5% arm achieved the IGA 0 or 1 with the two-point grade improvement, 39% in the 0.75% arm, and 7.6 in the vehicle arm. That was very exciting data.
Well, how about the EASI-75, which is another very common efficacy variable. That's shown here in this slide. Again, very similar pattern where you see a higher response rate in the 1.5% arm and then both arms shows statistical significance compared to vehicle. In TRuE-AD1, 62% of the patients achieved an EASI-75 by week eight, 56% in the 0.75% arm, and 24 or 25% in the vehicle arm. In TRuE-AD2, we see about 62% of the patients in the 1.5% arm achieved an EASI-75 score, 51.5% in the 0.75% arm, and 14.4% in the vehicle-treated arm. In terms of the mean % reduction in EASI score, that's shown on the next slide. You could slide the next slide, that would be great. There we go. I think, can you go back one? There it is. This is the EASI % change from baseline.
As you can see, this gives you a sort of a time course. You can see that 77%, or excuse me, the EASI reduction in the 1.5% arm in TRuE-AD1 was 77%, in the 0.75% arm is 72%, and in TRuE-AD2, the EASI reduction in the 1.5% arm was 75%, and a similar reduction was seen in the 0.75% arm, much higher than what was seen in the vehicle-treated patients. In terms of itch, the next two slides, if you go to the next slide, please, shows you the reduction in itch. As Dr. Eichenfield referred to, the inflammation is obviously a very important component that drives the pathogenesis. In terms of what the patient feels, it's really itch. We collected the itch scores. This is the change from baseline in daily itch NRS score.
As you can see, we see significantly greater reductions in itch NRS observed with both active arms. In fact, with the highest concentration, the 1.5, we see the reduction as early as 12 hours after the first application of rux cream. As you see, we're showing the first 28 days, the itch continues to improve throughout the eight weeks of the study, but as you can see, it's a very impressive reduction, and more importantly, a very rapid reduction in itch with the mean EASI reduction in the 1.5% arm of 3.39 in the TRuE-AD1, and 2.88 in TRuE-AD2. If you could go to the next slide. The next slide summarizes one of the major secondary efficacy variables that we collected, and that's the four-point improvement in itch NRS.
This is important because this is what FDA has defined as a meaningful endpoint in terms of itch reduction. As you can see, in both studies, we see significantly more patients treated with ruxolitinib cream demonstrated clinically meaningful reductions in their NRS4, or at least a four-point grade improvement in their NRS itch versus vehicle. By week eight, in TRuE-AD1, we see 52% of the patients in the 1.5% RUX arm are able to achieve this efficacy endpoint, about 40% in the 0.75% arm, and 15.4% in the vehicle-treated arm. In the TRuE-AD2 studies, in the 1.5% arm, 50.7% of the patients achieved this endpoint, 42.7% in the 0.75% arm, and 16.3% in the vehicle arm. Very exciting data as well.
If you could go to the next slide, I'd like to finish up the presentation to conclude and to provide the conclusions from what we saw in this study. What we see in this study is application of RUX cream brought about a rapid and substantial and sustained itch reduction, which was very exciting to see for patients. In terms of the efficacy, RUX cream showed superior efficacy versus vehicle in all of the major efficacy endpoints. In terms of the itch and the inflammation, I think this is the first time that we demonstrated a dual mode of action for RUX cream. It not only displays the anti-inflammatory activities you would expect with a JAK inhibitor, but also the anti-itch, antipruritic activities. In terms of safety, again, we're very excited to see that RUX cream was very well-tolerated.
We didn't see very many local side effects, nor any evidence of systemic side effects. Very excited about the data from both studies. We think that the data will support the application of RUX, excuse me, the submission of RUX, and we're hoping to move that forward later this year. I'd like to turn over the presentation back to Hervé.
Thank you, Jim. Yes, the next step in the program is to get the long-term safety data. When this is available to us, we intend to submit the NDA seeking approval in atopic dermatitis before the end of this year. The last slide here summarizes the commercial strategy and the exciting opportunities that we see for ruxolitinib cream in the U.S. If approved by the FDA, we expect to launch in atopic dermatitis late next year and in vitiligo in 2022. We plan to create a dedicated dermatology division. We will be targeting our efforts towards the 8,000 or so medical dermatologists using a specialty field model. Okay, operator, that concludes our prepared remarks. Please give your instruction and open the call for Q&A. Thank you.
Thank you. We'll now be conducting a question- and-a nswer session. We ask you please ask one question and, if needed, one follow-up, then return to the queue. If you'd like to be placed into question queue, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Once again, that's star one to be placed in the question queue. We ask you please ask one question and, if needed, a follow-up, then return to the queue. Our first question today is coming from Cory Kasimov from JP Morgan. Your line is now live.
Hi, this is Gavin for Cory. Thanks for taking our call. We just wanted to understand the key barriers to commercial adoption for this product. We had one follow-up as well. Thank you.
Hervé, do you want to take that one, the key barriers to commercial adoption, and maybe Dr. Eichenfield, if you can add? Hervé, are you on mute?
Oh, okay. Sorry, I was on mute. As you know, the number of patients we are potentially able to treat here is very large. These are patients who today have unsatisfactory treatment, sometimes with steroids. There is a question of really addressing that need. You can see the efficacy data in terms of itch and anti-inflammatory effect is really key to understanding why this product could be really changing the options for these patients. As we discussed, our plan is to really work with medical dermatologists at launch for the first months, if not years, of the launch of this product to educate everybody on how it could be really helpful. On the other end of the spectrum, when you go to the severe type of atopic dermatitis, obviously using injectable antibodies is today one of the options.
What we are also looking at is that for patients who have a limited size of a lesion, that using a cream could be also a very good option. As you can see from the clinical result. The lack of systemic exposure is leading to a very interesting efficacy safety ratio for this strategy. Maybe Dr. Eichenfield, if you want to complement that from your experience.
Yes, certainly. I think that when we see a new drug maybe on the launchpad in the dermatologists and to a degree, more primary care physician, people are looking to see, okay, how would this complement what I have now? Is it going to have something different that's really additive? I think that's the hard part in rolling out is to make sure that a drug is bringing something new and novel and better as it fits its way in. What's very exciting about this data is that we don't have, number one, there's very limited efficacy to the non-steroid medicines that we use.
They're just not that strong in terms of their impact on eczema and the data set actually, it's hard to know without living within these data sets, but the EASI score, the separation from the vehicle response to the active looks really, really good. Both the absolute EASI score decrease, the % change, as well as the % of patients who get a lot better, that EASI-75, meaning those people are getting 75% better. With a non-steroid, we don't have to worry about atrophy. You don't have to worry about steroid and cortisone absorption. This can be used across the spectrum of eczema. Patients with milder and more localized disease could use it as an alternative or in addition to regimens with topical steroids.
More severe patients, we may be able to prevent people needing systemic therapy or even in those on systemic therapy where even dupilumab, which has been a marvelous drug, there's a lot of surface area left on it. Across the spectrum, I think it can be taken up. I think the novelty is what looks like the relative efficacy. The other thing is their topical side effect data is where you're seeing stinging and burning that's higher in the vehicle in one of the two studies or around the same. That's remarkable because if the drug's well-tolerated, it also means there'll be a lot of excitement to people using it.
Okay. Next question, please.
Thank you. Our next question is coming from Marc Frahm from Cowen & Co. Your line is now live.
Hi. Yes. Thanks for taking my questions and congratulations on the data. Maybe one just technical thing for Jim. In the patient disposition slide, it noted that for TRuE-AD1, the analysis was done on an ITT basis versus in TRuE-AD2 some patients were excluded. Can you describe why some patients were excluded and then also if you did analyze TRuE-AD2 on an ITT basis, would any of the primary or key secondary endpoints like itch have lost statistical significance?
Sure Marc. You did notice that there were a decreased number in the efficacy analysis. During routine monitoring, a quality issue was identified at one of our sites in Europe. We did a thorough investigation, and it looks like there are some quality concerns around the data that comes from that site. We've decided to actually remove that site from the efficacy analysis. That analysis by removal of the site, that actually lowered all of the top line efficacy in the rux arms, but we felt it was the right thing to do. In terms of the imputation method that was used, this was the NRI. We used the most conservative, which is actually what we used in the phase II study as well. When you take a look at the protocol analysis, actually all the numbers go up.
If you use an LOCF, the values actually all go up. We're actually sticking with the NRI analysis because it's the most conservative.
Thank you. Our next question is coming from Brian Abrahams from RBC. Your line is now live.
Hi there. Thanks for taking my question and congratulations as well on the data. Dr. Eichenfield had mentioned the many comorbidities associated with atopic derm like sleep disturbance, et cetera. I was just wondering if you're seeing any concurrent benefits in these phase III on quality of life scores alongside the lesion and itch improvements as well as on SCORAD, which I know is important for Europe. Just as a follow-up, your level of confidence that you'll be able to collect adequate reliable data in the long-term follow-up, just given the current pandemic and how you're managing through potential challenges there. Thanks.
Sure. This is Jim. Yep, absolutely. We did collect a number of additional PROs, including quality of life. That data is still being analyzed and collated, and we'll present that data at a future scientific conference. In terms of the potential impact, you're right, as we mentioned, we're monitoring the situation very closely. We're putting into place and working with the sites to try to get the patients in within their visit windows. Right now, we don't have a full measure of what the potential impact is. In terms of the specific long-term data, yeah, we're still monitoring that. The goal is to submit the NDA by the end of this year. Right now, we still have that on track. Obviously everything will depend on what happens with the COVID-19 situation.
Thank you. Our next question is coming from Salveen Richter from Goldman Sachs. Your line is now live.
Thanks for taking our questions. This is Andrea for Salveen. Maybe just one for Hervé. If you think about the benefit that was demonstrated by both of the doses, how are you thinking about the regulatory path forward? Are you planning on seeking approval for both doses? Or how are you thinking about that?
Yeah, maybe Jim can speak about the regulatory. You saw from the data that obviously both doses are very effective, and it looks like on most of the endpoints that we have seen today, the higher dose is showing a little bit more efficacy, and there is really no difference in safety. That's really what we see from the data. Now, how the FDA is going to look at it is frankly something that I would say is difficult to predict. I think the decision, at the end of the day, will be made together with the FDA. Jim, do you have any thoughts on that?
No, I think that's a great summary. Yeah. No, I think that's right. I think we have some additional analysis that are ongoing. We'll have the long-term safety data. That'll all come into play, obviously, in terms of the dose. I think Hervé's right. It'll be a negotiation with the FDA when we submit.
Okay, Kevin, next question please.
Our next question is coming from Alexander Duncan from Piper Sandler. Your line is now live.
Hi. Thanks for the question. Could you provide any information on how much RUX cream patients used on average or on a % BSA basis, and if there were any site-specific differences or types of lesions in terms of where RUX cream works better? Thanks.
It's a great question. We're still analyzing the data. We're still doing all of the sub-analysis, including amount of drug. All of that is being done now and will be shared at a future scientific meeting as well as future publications.
Thank you. Our next question is coming from Jay Olson from Oppenheimer. Your line is now live. Mr. Olson, perhaps your phone is on mute.
Oh, thank you. I was on mute. Congrats on the data. Really impressive P values. Thank you for the presentation and taking the questions. If I could ask Dr. Eichenfield, could you describe the factors that would drive preference for a topical JAK inhibitor? Are they mostly related to the body surface area involved, or do comorbidities also play a role? Like if patients present with atopic dermatitis plus asthma or food allergies, would that make you more inclined to treat with a systemic therapy? As a follow-up, can you talk about the systemic long-term adverse effects that are associated with high-dose topical steroids? Thank you.
Sure. There may be an evolving approach to considering comorbidities in the decision tree for systemic therapy. One of the issues that I think we've seen Regeneron and Sanofi deal with dupilumab, is they have a drug that's approved for more than one Th2-associated disease state, but they sort of had parallel programs. In the dermatology world, people are sort of aware of the comorbidities, but they don't necessarily want to manage them. I don't think that makes a big play for a decision for systemic. I think probably the biggest thing is that being able to bring different regimens in that will have more effectiveness, where one could use non-steroids in long-term disease control more effectively because the present ones have their limitations, and/or a mix and match between that.
There'll be a subset of patients who can be really well taken care of with the systemic effects of topical corticosteroids really relate to the strength and quantity. The politically incorrect analogy is alcohol. If someone says, "I drink wine every night and a bottle lasts five months," I mean, the wine will go bad, but I won't worry about the quantity imbibed. The problem with topical corticosteroids, the difference between an over-the-counter or lower strength prescription topical corticosteroid, which are 1% or 2.5%, hydrocortisone, for instance, and 0.05%, numbers don't correlate. clobetasol's about 20x stronger. You truly can get, continuously in large quantities, then you could get absorption. What happens, cortisol's produced, so your adrenal glands stops working. Very uncommon in clinical practice to have so much systemic corticosteroids, yet that can occur.
A consequence of that is that there's underuse of a corticosteroid, I'd say, because people are so fearful of it. While it's great for us to encourage use of topical corticosteroids as part of regimens of care, effective is really having a move to other patients or a mix and match depending upon the disease severity so we can bring long-term disease control, and I think that's where this product six is something very exciting that will allow more patients to be managed effectively without the need for systemics.
Thank you. Our next question is coming from Reni Benjamin from JMP Securities. Your line is now live.
Hi. Thanks for taking the questions and congratulations on the data. Just one for Dr. Eichenfield. You have quite a few options on your hand, and I'm kind of curious. A newly diagnosed new patient comes into your clinic, just what is the gamut that you run through before you get to, let's say, prescribing a RUX cream or a Eucrisa? How many options do you go through? Is this like a last-ditch option that you give these patients, or do you start moving it up front line? Then as a follow-up, maybe for Jim, you have 50% of patients that are not considered IGA responders. Are any of those patients getting better over time? Do you wind up switching them to other medications? Thanks.
Okay. The when-use question is something that, I have to be honest, where in talking a lot to both people and company people often want to know, "Oh, is this first line? Can this be first line?" I say: Don't fight line as a label. I mean, as a verbiage, because someone who comes in for new onset atopic dermatitis for the first time, they're probably going to get a cheap topical corticosteroid to see how quickly we can get the disease under control. Then see what happens, because whether it will come under control and then stay under control, or is it one of those persistent cases where if they stop the topical corticosteroids, there's recurrence. That's almost besides the point, because there's so many who aren't managed by just a week or two of topical corticosteroids and a little topical corticosteroid now.
If you had that's one thing. See patients where that regimen doesn't work. If I have a patient who's a new patient for me who has a history of use of corticosteroids, which is usually the case, even if they're too little, it's very early, maybe visit or second visit that we'll prescribe a non-steroid like this in the regimen of care. Many times, it's the first time. Especially you have to realize that there's topical corticosteroids on the face issue. Around the eyes, they can cause cataracts and very thin skin on the body. A well-tolerated medicine that's not going to have that and yet can still control the eczema area, very exciting. Yeah.
Yeah, the second part. Sorry.
The question was for Jim, I think. Go ahead.
That's right. The question was around the % of patients that weren't able to achieve the IGA score, IGA treatment success at week eight. I think in the study schematic, it showed you that all patients were on active drug, either the 1.5 or the 0.75 beyond week eight. We'll be able to collect those patients and see how many of those patients who didn't hit the IGATS at week eight, and how many of them are able to achieve that at subsequent visits. I will add though, that this is the first time, I think any product has been able to achieve an IGA zero one with a two-point grade improvement of into fifties. Larry, correct me if I'm wrong, but I think this is the best efficacy that any product has been able to achieve in an AD study.
I would just qualify the IGA of 50% as probably some of the best efficacy that's been seen so far. Just wanted to add that in there.
Yeah. I totally agree. The IGA scores, the FDA approach is what percentage of people get approved pretty clear. A high bar, but if you look at it, that's why you look for the absolute EASI decrease, an absolute increase of 75% improvement, an EASI score of around 8 is marvelous. You're down to really low numbers.
Thank you. Our next question is coming from Vikram Purohit from Morgan Stanley. Your line is now live.
Hi. Good morning. Thanks for taking my question. I have one for Dr. Eichenfield. I wanted to go back to a question on commercial considerations and thinking through uptake. If the product is eventually approved, but is approved with a black box warning, due to it being a JAK inhibitor, how do you think uptake would be impacted versus if the product were approved without a black box?
The easy answer is it's hard to know that. A lot will be on what the sensibility is of the safety data that comes with it. Dermatologists are way more sophisticated now with what box warnings mean since there are an expanded number of boosts that may have them. I think if the safety data for the drug itself does not show signs of systemic effect, no systemic immunosuppression, none of the side effect concerns that may get labeled for what you see with our oral JAK inhibitors or oral RUX. If it's labeled, but that's not seen in any of the population, I'd feel very comfortable using it.
We totally live in this world of the notion of side effect profile between topicals and systemic, delivering efficacy locally to areas that are inflamed without taking the systemic approach to try to avoid systemic side effects. I think if the safety aspect of this, which looks so good, remains that way, it will allow them to move forward, at least in the hands of most dermatologists. Now, if there's a requirement for monitoring, that might be a big barrier, but I wouldn't foresee that happening.
Thank you. Our next question is coming from Matt Phipps from William Blair. Your line is now live.
Thanks for taking my question. Just curious with this rapid response you see in skin involvement, does that essentially mean that the amount of cream used, I guess, as in grams or such, will show a similar pattern, just assuming there'd be, I guess, much less volume being used by eight weeks as opposed to when these patients start with about 10% BSA?
Sure. This is Jim. Could you rephrase that? I want to make sure I want to answer your question. Are you asking around, do you think the cream, because it is topically applied directly onto the skin, that is the explanation for the rapid response and its reduction?
No. Sorry. Just as far as volume being used and thinking about ultimately pricing it versus a tube and how much patients are using, and that's just this rapid response leading to just the patients not needing as much volume over time.
I-
to cover the
Sure
surface area.
Yeah. That's a fair question. In terms of the clinical trial, we'll obviously provide an instruction, and we're looking at the compliance of the patient in terms of dosing. I think maybe that's more of a question that I can ask Dr. Eichenfield to address in terms of patient compliance in the real world.
Yeah. Well, first of all, patient compliance in the real world's fairly miserable, but that's one of the issues, just partially because they're fearful of their medicines. What normally happens, I think with any of our topicals, is that we'll start off with a higher quantity of use over the first week or two of the treatment, and then if you have an effectuation, you start to get skin healing, then you'll decrease the quantity you use as parts of areas heal. Many times, for many patients, we go into maintenance mode, what we call proactive treatment, sort of using the asthma model, where we don't wait for patients to flare and start wheezing again before we treat to keep their wheeze away. In atopic dermatitis, there are these hotspots that may recur.
If you've cooled them down, then they may use the drugs intermittently in that fashion, not the way this drug is studied at this point in the phase III studies. It's not as though people will turn off their use totally, but there will be a higher volume of use probably in the first few weeks, but that's because you're bringing healing to that portion of the skin. Over the long term, there should be continued use, not just for flare control, but in this long-term disease model.
Ladies and gentlemen, we have time for three more questions. Our next question is coming from Michael Schmidt from Guggenheim Securities. Your line is now live.
Hey, this is Kelsey on for Michael. Thanks for taking our question. We were just kind of wondering if you could provide some of your thoughts around existing payer control in the AD space, and maybe kind of some color around your strategy to secure patient access. Thank you.
maybe-
The first part of it I missed. I'm sorry.
Oh, that's okay. I can go back. Yeah, just kind of thoughts on existing payer control in the space, and kind of your strategy to secure strong patient access.
Sylvain, do you want to try that one.
Take it from my standpoint, and then we'll turn it over to Jim for the real answer. As a clinician, we spend more time and energy and staffing trying to get drugs approved, but it's usually, there are two ways of doing it. There's patient by patient, and then there's group by group or payer by payer. Increasingly, if it's standardly used in regimens of care, then we can get it approved. Now, many times, they may require that someone's used a topical corticosteroid to get a non-steroid, but that's not a problem as long as you document it. There's advocacy that needs to be done, but that's pretty much part of the standard of what we do in practice.
Like any new product, there is a phase where we will be working with the payers to try to see where they see this new product in the step edit program, what prior therapies they would need to see, et cetera. It's a very classic phenomenon, is that as we go through the first months of the launch, there will be more and more availability of the product earlier in the disease. On the pricing side, we have not made a decision on where it's going to land. That will be done later when we are closer to the launch date. Obviously, the goal is to have a product that will be widely available because we believe the benefit
Of this cream can be seen in a very large number of patients with atopic dermatitis.
Thank you. Our next question is coming from George Farmer from BMO Capital Markets. Your line is now live.
Hi. Thanks for taking my question. I wanted to talk a little bit about systemic exposure and whether you actually looked at systemic exposure and whether application of the drug, perhaps on open lesions, might increase any risk.
Sure. This is Jim. I'll take that. I think Dr. Papp mentioned it during his presentation. We're still working on getting the PK data. We did collect PK during the vehicle control period. That data is being analyzed, and we'll share that at a future scientific conference. If you take a look at the adverse event profile, clearly, it's hard to see if the systemic exposure was clinically meaningful, as we didn't see any side effects associated with that. Then in terms of the open lesion, we'll see. We'll see with the PK data. I will share with you that the PK was also done in the phase II study, and that data or that information was shared in the phase II publication, the manuscript.
Thank you. In the interest of time, we have time for one further question. Our final question today is coming from Tazeen Ahmad from Bank of America. Your line is now live.
Good morning, guys. Thanks so much for taking my question. Congratulations on the data. Maybe one on the question of commercialization. On the competing drug that's on the market that's applied topically, one of the complaints that physicians have had is that patients sometimes complain that the cream can be messy. Based on the comments that were made already on the call, is it your view that a cream is something that would be more attractive to patients who potentially have less of their skin involved in a breakout, or do you still think that once a patient gets to a maintenance level, that the amount of cream that he or she might need to use would decrease over time? Thank you.
Dr. Eichenfield, do you want to take that one, and Jim, maybe a follow-up?
Sure. First of all, we know if you ask dermatologists, they prefer ointments over creams. Patients clearly prefer creams over ointments, and that's partially because the sort of gooeyness aspect of it really matters to them. Most patients recognize that there's a part of their skin that's not just the inflammation, that has dryness as well. Some degree of skincare is part of the obligation. Trying to make it as minimal as possible is what we're going for and what patients want. People are going to be looking for efficacy, number one, efficacy and whether it can be put in a regimen of care that's not going to create a burden of work. Which itself will decrease inflammation. People will use it in regimens of care. As I said, they might use less over time, but that's fine.
We're going to have more patients who use more proactive therapy, as I call it, treating to keep inflammation from coming back. That's fine. If they only need a small amount of product for that's marvelous because it decreases the burden. People are trying to minimize the disease, they also want to minimize the work they need to do to do that. You want an effective product that will aid it. I think that's very important. Jim?
Yeah. The only thing I have to add, I think that's a really good description. I think the only thing I have to add to that is that our cream itself is very cosmetically elegant. It's vanishing. Doesn't leave any tackiness or sheen. I think patients will find it very acceptable from a cosmetic perspective, aesthetic perspective. I think Dr. Eichenfield's absolutely right. I think ultimately it's really going to be finding something that works for the disease to provide that both the acute but also the long-term control. Obviously, if you have 50% of your body of surface area involvement, a topical doesn't make a lot of sense because it's very impractical to lather yourself up on such large areas.
I think for the vast majority of AD patients, I think a topical product makes a lot of sense and is probably, as Dr. Eichenfield mentioned in his presentation, still where the greatest unmet need is. With that, I'll turn it back over to Kevin.
Thank you. We've reached the end of our question- and- answer session. I'll turn the floor back over to Mike for any further closing comments.
Okay. Thank you all for participating in the call today. The IR team and I will be available for any follow-up questions that you may have. I know we weren't able to reach all of the analyst questions that were polled for. I'm sorry about that. For now, we'll close the call. Thank you.
Thank you. That does conclude today's teleconference and webinar. You may disconnect your line at this time and have a wonderful day. We thank you for your participation today.