Greetings, and welcome to the ruxolitinib cream phase II data in vitiligo webinar and conference call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Mike Booth, Head of Investor Relations. Please go ahead, Mike.
Thank you, Kevin. Good morning, and welcome to our conference call and webcast to discuss vitiligo, the disease, the medical need, and the biological rationale for JAK inhibition as a potential therapy. We will also provide some highlights from the presentation of the phase II data from ruxolitinib cream as a treatment for patients with vitiligo that were presented at the World Congress of Dermatology over the weekend. The slides used today in today's webcast are available for download on the investor section of incyte.com, as are the full data slides as presented in Milan on Saturday. I'm joined on the call today not only by Hervé and by Jim Li, our Head of Inflammation and Autoimmunity development, but we're also delighted to welcome Dr. John Harris from the University of Massachusetts. Dr. Harris is a world-renowned expert in vitiligo.
He is an Associate Professor and Vice Chair in the Department of Dermatology and the director of the Vitiligo Clinic and Research Center at the University of Massachusetts Medical School. Hervé will begin the call today with a few opening remarks before Dr. Harris provides us with some important context on the disease of vitiligo, the evident unmet medical need, and the rationale and potential for JAK inhibition to be the first approved therapeutic for the disease. Jim will then provide some highlights of the ruxolitinib cream phase II data set before we open 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.
Before we begin, however, I'd like to 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, including in our Form 10-Q for the quarter ended March 31, 2019. We'll now begin the call with Hervé.
Thank you, Mike, and good morning, everyone. Incyte clinical portfolio is organized around three pillars. We have in oncology targeted therapies and immunotherapy. Several years ago, we built a new group of 10 or 15 scientists to review the use and indication for products coming out of the research and review where they could have applications outside of oncology. That was the goal we gave them of saying, you have this immuno-impacting type of a mechanism coming from our research. Tell us where it could apply outside of treatment of cancer. That's what gave rise to our Inflammation and Autoimmunity Development group, which is now headed by Jim Lee here today as part of Steven Stein's organization. We have small proof-of-concept trials already underway in several indications for our oral JAK and oral delta program.
Most advanced programs in this IAI franchise are with ruxolitinib cream. We have phase IIIs ongoing in atopic dermatitis and are recruiting well, and we'll have data from this phase IIIs in the first half of next year. Now we have a successful phase II in vitiligo, which is the subject of today's call. If you remember last year, we had an R&D Day reviewing the full portfolio of Incyte. This year, and this will be the first instance of that, we want to replace it with more thematic TCs based on the news flow. Today will be around the proof of concept in vitiligo, and I would like to welcome Dr. Harris to the call to start the presentation.
Good morning, everybody. Thanks, Mike, for that nice introduction. Just to remind everybody, I'm a physician scientist who studies vitiligo. I see patients a half day a week in my vitiligo specialty clinic, and then I run a research laboratory to better understand what causes this disease. Vitiligo is an incredibly common disease. It affects about one to two in 100 people. That's a lot of people in the U.S. and around the world. Half the patients who get vitiligo do so before the age of 20. As a physician, I'm managing patients over many decades of life, then we have to think about treatment in terms of decades. As a scientist, it gives me an opportunity to study this disease over a long period of time.
Vitiligo has a lot of disease associations, as we study this disease, we believe that we're studying the mechanisms of other autoimmune diseases as well. This is a typical presentation of vitiligo, called patchy depigmentation. This is on the hands, as you can see here. It can become more widespread in some cases as well. We'll talk about the surface area of vitiligo and how it can present in different patients a little bit later. The great news about vitiligo is that it's reversible. This used to be a white spot. You can see that there's repigmentation here, coming back as little brown spots, and this is how it repigments. The reason why the spots come back as they do is because the melanocyte stem cells live within the hair follicle. This is where the vitiligo repigments from, as you can see here.
You can see, really, we can get very nice responses. It can take a very long time, however. This is a patient treated with narrowband UVB. Top left to bottom right is over a year. She got very nice repigmentation of her neck and chest. Was very happy with this. She said she was wearing low-cut dresses again. It completely changed her life. What I'm not showing you is the repigmentation on her face, which was complete, 100%, to the point where I could not even remember that she had vitiligo on her face. In talking about the effect of vitiligo on patients, it is huge. We published a paper called "Vitiligo is Not a Cosmetic Disease," and the title is specifically to call attention to this, because sometimes in the past, it has been dismissed as such. It's actually a well-known mechanism.
It's an autoimmune disease, similar to psoriasis and alopecia areata, type 1 diabetes. We know that these run in families, and so we understand the mechanism. It's clearly a disease, whereas cosmetic treatments or cosmetic issues are things that we all struggle with as we age, whether it's wrinkles or thinning of the hair, et cetera. Vitiligo, it's clearly in a separate category. In the second paper shown there, "The Burden of Vitiligo," concluded that vitiligo is a serious skin disorder with an adverse impact on an emotional state comparable with that of other major skin diseases. I think it's clear that vitiligo does not deserve a separate category as being any milder than the other diseases that we currently treat.
On the right, we have a study that looked at vitiligo patients and psoriasis patients, and their quality of life using the Dermatology Life Quality Index. I like this study because it's a direct comparison and shows the effect on quality of life in both diseases. Vitiligo patients who are affected either moderate to severe to very severe is 51%. In psoriasis patients, that number is 56%. They're actually quite comparable in terms of the impact on quality of life in both diseases. Both diseases deserve to be treated. The unmet medical need in vitiligo is clear through the poor quality of life. As I mentioned, it's similar to psoriasis, but also eczema. Actually, there are studies that show that the willingness to pay for a cure from patients is higher in vitiligo than even in eczema.
That's the amount that someone is willing to pay out of pocket to cure their disease, and so it just shows the impact of this disease. There are no FDA-approved medical treatments to improve vitiligo. There is one FDA-approved medication called monobenzone. It's a cream that actually makes vitiligo worse. It's what Michael Jackson used to bleach his skin. We certainly must do better. We use off-label topicals right now, and they have side effects that we'll talk about in the next slide here. The current vitiligo treatments are listed here. The market is segmented and incomplete. We are not able to take care of all of our patients for the limited efficacy, the burden that it puts on patients in phototherapy, I'll show you, and then also the side effects of these treatments. The oldest treatments that we have are topical steroids.
They can be effective. With continued use, they cause stretch marks or striae and atrophy of the skin. Dermatologists are very careful with topical steroids. Non-dermatologists are actually quite fearful of topical steroids and refuse to use strong steroids in their practice. Topical calcineurin inhibitors are newer. They don't have the same side effects as steroids, although they are symptomatic. They can cause a burning sensation, which has caused discontinuation. They often cause hyperpigmentation around the edge of the border, and so people have concerns about using them as well. Narrowband UVB phototherapy is currently the best therapy that we have. It requires a visit to the dermatologist's office two to three times per week for over one year, as you can see. Very time-consuming, very difficult for patients to take time out of their schedules to do this.
We have moderate efficacy, and we can talk about that. Surgical transplantation is there just for completeness. It is only for patients who have very stable disease, which is a very small population of patients, but we can actually transplant pigment cells from one part of the body to another as a treatment. It only helps less than 5% of the patient population, and it's only conducted in three locations in the entire U.S., so there's not a lot of access to it. Then depigmentation, I mentioned earlier, this is the monobenzone cream. We only use this if the disease is very severe. This represents a very small part of the population with vitiligo, and it actually worsens the disease, and so it's not commonly used.
In summary, the current treatments that we have, they have pretty significant limitations due to side effects in the population which they are useful. At this time, without an FDA-approved treatment, we believe we've penetrated only a very small part of the market. We estimate less than 0.5% of the total market. Next, I put here just my simple treatment algorithm. This is how I treat vitiligo. First, I look to see if it's active, and if it is, I give some oral steroids for a short period while we get patients on something else. If it's not active, or after we put on the steroids, we look at the total body surface area. If it's greater than 5% body surface area, or if it's not greater than 5% body surface area, we'll use topicals alone.
Right now, we have to use clobetasol because it's the most effective treatment that we have, but because of the side effects, we have to use it in a discontinuous manner. We will use clobetasol for a week, and then we'll use tacrolimus for a week back and forth, and we continue alternating in this way. It's very confusing for patients, and tacrolimus doesn't have the same efficacy as clobetasol, which is why we use it this way. It's complicated because we can't use the strong steroids continuously. For focal disease, we can also consider excimer laser as a phototherapy option, and as I mentioned, surgery. If the body surface area is covered greater than 5%, then we strongly consider narrowband UVB. If the patient has access to it, they'll do that.
If they don't, we'll just continue to treat them with topicals in a smaller area of their body. If they'll use UVB and topicals, we certainly do that because we see better efficacy when you combine topicals with UVB. If they're not willing or able to apply topicals, then we just use phototherapy. The question frequently comes up in this avenue, in this venue, how many patients actually have less than 5% body surface area and can be treated with topicals alone. Three specialty clinics around the world gathered data, including mine, Amit Pandya's clinic in Dallas, Texas, and Philippe Azoulay's clinic in Paris. Actually, we analyzed the body surface area of our patients in that breakdown. It was really very interesting. In these different areas of the world, we had very similar numbers.
The number of patients who had less than 5% body surface area was 58% of our patients. Those are patients that we would Most of those patients we would start on topicals alone. The remaining population, 42%, have greater than 5% body surface area. Those patients, we try to get onto narrowband UVB phototherapy, we also combine topicals. This is a summary of how we would use FDA-approved treatments in the future, assuming we had a topical and a systemic available. First, we would look for signs of activity. If they were present, we would use a systemic plus topical. We estimate this would be 20% of the population. If there were no signs of activity, there was less than 5% body surface area, we would use a topical alone. That would be about 48% of patients, we estimate.
Those without signs of activity, be more than 5% body surface area, we would use a systemic and topical again, and that's about 32%. The take home here, though, is that a systemic would probably be used in about half of patients, but a topical would be used in 100% of patients. This is what we do today, even. If I have a patient with widespread disease and I put them on a phototherapy, full body therapy, we add in topicals as well. Those that would be eligible for a topical is every patient. Currently, therapy for vitiligo is reimbursed at a high level, even though we don't have FDA-approved treatments. We use narrowband UVB. It's reimbursed at $24,000 per year. Excimer laser is reimbursed at $42,000 per year. We do get coverage for patients even though we don't have the approved therapy.
The opportunity in vitiligo, I think, is probably best appreciated if you compare it to psoriasis, which is another disease that has grown significantly over the last 25 to 30 years. 30 years ago, psoriasis was in the same place that vitiligo is now. We were treating with topicals, phototherapy, oral immunosuppressants like methotrexate. Now, psoriasis is an $8 billion market shared by 10 to 12 drugs, many of them biologics, and the market is expected to grow significantly in just the next few years. Part of the reason for that is the very highly effective biologics that have now been developed. Psoriasis is in 2%-2.5% of the population. Vitiligo is similar to that, 1%-2%. We estimate a large unmet need there in the vitiligo population. As I mentioned, there's no effective FDA-approved medication for this disease.
To introduce the rationale for targeting JAKs in vitiligo, I've put a few slides here on some of our work. We developed a mouse model of vitiligo early on, about 10 years ago, where we adoptively transferred autoreactive T cells into a mouse that has black skin and black hair. Over six to seven weeks, we see white spots appear. You can see them on the tail. They're on the feet, the nose, and the ears of these mice. We're able to quantify that. The mouse model actually is a great representation of human disease. The clinical and histological appearance is the same. Gene expression, which I'll show you in the next slide, is the same in mouse and human skin. It's the only mouse model that we have of skin depigmentation. Others cause hair depigmentation, which is a different animal altogether.
It's the only reversible model of vitiligo that we have. To be able to test new treatments that reverse disease, we need to use this model. We have found that ongoing studies, including the one we're going to talk about today, parallel observations in mouse and humans, so the drugs that work in mouse work in human. The mouse model has predicted JAK inhibitors that are now in clinical trials, that they would be effective. We use this model actually now for many companies that want to perform preclinical testing. This is the gene expression profiling that we did early on in the mouse and human skin. We can see a loss of melanocyte transcripts, as you'd expect to see in vitiligo, and then the other obvious pathway that's turned on is interferon gamma and the interferon gamma-induced genes.
We see nothing from the type 17 immune response or the type 2 immune response, and this is where we have psoriasis drugs and dupilumab for atopic dermatitis. This really predicts that those drugs would be ineffective for vitiligo, and that's what we find. At least psoriasis drugs have been thrown at vitiligo many times, and they're completely ineffective. We need drugs that target this interferon gamma pathway, which is the vitiligo-specific and relevant pathway. Based on this data, we hypothesized that interferon gamma was really the driver of this disease in mice. We found that was true. If we knocked down interferon gamma, the receptor for that, we were able to prevent vitiligo in the mice.
If we knocked out a downstream chemokine CXCL10, which on the previous slide was one of the highest expressed gamma-induced genes, we also found that that prevented disease. Probably more importantly, we found that even if we let disease continue, this used to be a black tail on the top, turned completely white through vitiligo. We blocked CXCL10 or interferon gamma or other things with an antibody, and we found that the pigment came back. We got perifollicular repigmentation on the tail as we see with those treatments in humans. We were very excited that we had identified the key pathway that drives vitiligo. Summarized here, interferon gamma initiates the pathway. It signals through the interferon gamma receptor. JAKs one and two are required for intracellular signaling through this receptor.
They activate STAT1 and then turn on chemokine CXCL9 and 10 and others that signal through CXCR3 and recruit more T cells to the skin. This creates this positive feedback loop that drives the progression of vitiligo. We have found, over the last 10 years or so, that when we knock out interferon gamma, the receptor, STAT1, the chemokines or the receptor for those chemokines, we are able to prevent disease, really indicating that this pathway is important to development and progression of vitiligo. We have also found that if we use antibodies to the soluble factors of the receptors, we can not only prevent disease, but we can reverse it, which is fantastic and clinically relevant. Then, most importantly for today, we found that JAK inhibitors are effective in our mouse model. I will not take the time to show you the data.
We have not published that data. They're highly effective in the model. They prevent and reverse disease. Next, we put ruxolitinib, oral ruxolitinib in a patient with vitiligo. See here, on the far right, you can see before and after treatment, five months of treatment, the amount of repigmentation he got. He had almost nothing left on his face, and he nearly completely repigmented in just a few months. This was about 50% improvement, actually. We had saved up his serum over a year before this treatment, and we found that his CXCL10 level, that interferon gamma-induced chemokine, was very high and stable for over a year in this patient until he started the ruxolitinib treatment, and then it dropped.
Not only did we see that ruxolitinib was effective in a patient, but we saw that it seemed to be working the way we hypothesized with blocking interferon gamma and dropping the chemokine. This and other clinical studies have allowed for three ongoing clinical trials right now by Aclaris, Incyte, and Pfizer. We're talking about Incyte today, which is the furthest along by far. We had one more question because those were systemic therapies. We wanted to know whether topical JAK inhibitors would be effective for vitiligo. We're back to the interferon gamma pathway. The way we tested whether topicals would be effective, definitively and mechanistically, was to look at STAT1. We were able to remove STAT1 genetically, only from keratinocytes in our mouse model, and then ask, did this have any effect on vitiligo?
The question was whether the keratinocytes played a role in driving disease. This is how we did it. We put T cells into the black mouse again, but the black mouse, we were able to completely remove interferon gamma signaling by removing STAT1 only in keratinocytes. What we found was, if the keratinocytes cannot respond to interferon gamma, we were able to significantly protect from disease development and progression. This indicated to us that all we have to do is turn off interferon gamma signaling in keratinocytes alone, and we can have a big effect on disease progression and develop a treatment. This is what topicals do. Topicals hit the keratinocytes first.
David Rosmarin at Tufts used this as rationale to perform a small topical clinical trial that was published in the JAAD in 2017, where he saw significant repigmentation through topical treatment with ruxolitinib. That's the end of my presentation where I'm ready to transfer this back to Incyte.
Great. Thank you, John. That was a great presentation. What I'd like to do now is to provide some highlights of the presentation by Dr. David Rosmarin at the World Congress of Dermatology. He presented the phase II data this past Saturday, what I'd like to do is provide just some of the highlights of his presentation. I think as Dr. Harris mentioned, this was the first large randomized study in vitiligo. On the next slide, it provides a very high-level overview of the study design and some key inclusion and exclusion criteria. We evaluated three concentrations of ruxolitinib cream, the 0.15, the 0.5, and the 1.5. With the highest concentration, the 1.5% concentration, we tested both once a day and twice a day, and we compared it to vehicle cream.
That portion of the study against the comparison against vehicle cream was done for 24 weeks, that's the data that we're sharing today. After the 24-week visit, all the patients were crossed over to active therapy. They were crossed over to either continue with the two higher concentrations or the three highest dosing cohorts. Vehicle patients and patients on the lowest concentration were crossed over to higher concentrations. At week 52, all of the patients were started on the highest concentration of RUX cream, the 1.5% BID. In terms of some of the key inclusion/exclusion criteria, we tested ruxolitinib cream in adult patients with vitiligo. They had to have approximately half a palm of body surface area involvement on their face, and at least 3% of their total body had to have vitiligo.
We excluded patients that had other skin conditions that would have confounded any of the evaluations, as well as screening them, or at least requiring a washout period for previous therapies of their vitiligo. In the next slide, we highlight the key demographics and clinical characteristics of the patients that were enrolled in the study. You can see the average age was approximately 48, about a 50/50 split between women and men. In terms of Fitzpatrick skin type, about a third of the patients were darker-skinned individuals, Fitzpatrick 4 through 6, a third Fitzpatrick skin type 3, and a third Fitzpatrick skin type 2. In terms of the disease, Dr. Harris mentioned some of the clinical characteristics of patients that he sees. I think the clinical characteristics here provide a view of the patients that were enrolled in this study.
The total BSA involvement was 22, so 22 as a mean percent body surface area involved was 22%, so quite a high number. In terms of the length of disease that the patients had, the median duration of disease was 14 years. Dr. Harris mentioned that there are other autoimmune conditions associated with vitiligo. We had about 25% of patients who reported another autoimmune condition. In terms of prior therapies, about half the patients had been treated with topical corticosteroids, another half treated with topical calcineurin inhibitors, and about a third of the patients had received prior phototherapy. On the next slide, we present the primary efficacy variable, which was the facial VASI-50 response, so patients who achieved at least a 50% improvement from baseline in their facial VASI score. Couple points to highlight.
One, as you can see, you can see over time, the response continues to improve and get better. Interestingly, we see a response as early as week eight, and then at week 24, we see that the best response are in the two highest dosing groups, the 1.5% dose once a day and the 1.5% dose twice a day. One of the things that we've heard from feedback, and I think Dr. Harris mentioned, is that both physicians and patients truly want the best response for their vitiligo as possible. Another efficacy variable that we looked at was the VASI 75 score, which is shown here on this slide. This is the proportion of patients who experience at least a 75% improvement in their VASI score from baseline. Again, you see the same pattern.
You see the response show up fairly early at week eight and improve over time. In this case, you see that the best response was seen in the group that was dosed with the 1.5% cream dosed twice a day. About 30% of the patients achieved a facial VASI 75 at the week 24 time period. In terms of the safety that was observed in the study, that's highlighted here in the next slide. We see that ruxolitinib cream was very well-tolerated. We do see some reports of acne in the study, a low percentage, and none of them led to discontinuation from the study. Patients also reported some itch, both at the application site and at other body parts. In terms of the discontinuation, we had only three patients who discontinued due to adverse treatment events.
We had one patient in the vehicle arm and one patient in the lowest concentration, the 0.15% QD arm, that discontinued due to headache. We did have a serious adverse event occur in the 1.5% b.i.d. arm. However, that was not related to treatment. The patient actually injured himself and had to withdraw from the study. Overall, very well-tolerated in the first 24 weeks of treatment. The next slide is just a very high-level summary, the conclusions that we see from the study, we see that significantly more patients achieved a facial VASI-50 improvement after 24 weeks of treatment with ruxolitinib cream. In terms of the specific arms that achieved the best response, we see that the 1.5% dose twice a day and the 1.5% dose once a day both were significantly better than vehicle cream.
In terms of the facial VASI-75, again, the higher, more robust endpoint, we see that 30% of the patients in the twice-a-day arm and 16% or 17% of the patients in the once-a-day arm were able to achieve a 75% improvement in the facial VASI score at week 24. Again, from a safety perspective, we saw that the Rux cream was very well-tolerated. In terms of next steps, obviously, we're very excited about the data, and we're moving very quickly to initiate the phase III study. We hope to start the study sometime this year. Then, depending on enrollment, have the results sometime in 2021, with hopefully a submission at that time point. Kevin, that ends our prepared remarks. If you could please give the instructions for Q&A. Thank you.
Absolutely. We're now beginning to open up a question and answer session. If you'd like to be placed in the question queue, please press star one on your telephone keypad. We ask you to please ask one question and one follow-up. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove a 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 is star one to ask a question, and we do ask that you ask one question and one follow-up, then return to the queue. Our first question today is coming from Brian Abrahams from RBC. Your line is now live.
Hi. Thanks very much for taking my question and congrats on the data. I was wondering if you could talk about any interim results you saw on T-VASI scores, any reason to think that would trend differently? Do you have any clarity from regulators on what registrational endpoints might be? I'd love to hear Dr. Harris' views on that as well. Thanks.
Sure. This is Jim Lee. Great question. I'll start with your second question around the regulatory endpoints, and to say that we are working with both the FDA and the EMA to finalize the phase III study designs, and we'll share those shortly when we start the studies. In terms of the total VASI, we did collect, obviously, total VASI. As I mentioned, the average body surface area was about 22%. Patients were restricted to treating only 20% of their body, and we did collect the treated areas, and we'll provide that data at a future scientific meeting. Harris, if you want to add anything.
Yeah. Happy to add to that. In terms of the total improvement that patients are looking for, we've published this and we've done panels with patients, asking them how much improvement they want, and they consider 75% improvement successful therapy. That is not 75% at 6 months. It's 75% eventually by 1 year or more. Ultimate improvement, they want 75%. They said that they would be happy with 25% at 3 months, as long as they know that they're going to get more over time. In this study, we found that 30% of the treated patients in the highest group actually achieved a successful treatment in only 6 months, which is very fast. The VASI-50, with its upward projection at 6 months, we fully expect the 52-week data.
I would anticipate and guess, just based on the tracing, that it really improved significantly. I think we're completely within the realm of what patients want.
Thanks so much.
Thanks. Our next question today is coming from Marc Frahm from TD Cowen. Your line is now live.
Thanks for taking my question. Maybe Dr. Harris, we can follow up on that last question and point. I think in your studies and talking to patients ourselves, we see there is kind of a range of goals for patients. Could you maybe talk a bit about if you bucket the patients into the ones that are willing to accept, say, 50%-75% versus people who really want just full or near full repigmentation before they would want a therapy?
There is a range of patients. Some patients are very demanding, and they say, "100% or nothing." They're the minority for sure. The good news is actually that the face is capable of responding to 100%. What we see is the extensive response really varies by anatomical distribution. As I mentioned earlier in my talk, the repigmentation comes from the hair follicles. What we find on the body is the areas that have the highest density of hair follicles respond the fastest and the most complete to therapies, any type of therapy. The face has the highest density of hair follicles, the face actually is capable of responding 100%, as I mentioned in my patient. What frequently happens is after a successful therapy, I'll forget that the face actually ever had vitiligo.
That, fortunately, is the most important to patients, that their face is usually the most important area, and that location is capable of responding 100%. At the same time, there are other areas that don't respond at all. Fingertips with no hair follicles or the underside of the wrists and a very few other places that have no hair follicles typically respond 0%. What patients need to be educated on and their expectations set about what can be expected. The good news is, even the patients who want 100%, the small number who demand that much repigmentation, can get that on the face. That is achievable. It'll usually take a year.
Patients, the good news too is after three months, if they've got 25% repigmentation, they're on board, they're excited, and they'll treat for a full year to achieve the full effect. It's not that it takes a full year to see anything. We see improvement early on, and that continues at a pretty slow clip for the whole time.
Perfect. Thanks.
Thank you. Our next question is coming from Tyler Van Buren from Piper Jaffray. Your line is now live.
Thanks, guys. Good morning and congrats on the data. It looks great. I guess. More of a commercial question. Can you guys speak towards your potential capacity to launch and strategically how you would do that? How much resources you'd have to put forth upfront, and how you would change that over time? Just briefly, maybe as a follow-up, is there the ability to price differentiate in vitiligo versus atopic derm?
Okay, thanks. I will take this one. Starting with your last question on the pricing, obviously, the phase III are ongoing already for atopic dermatitis. There are two different concentrations that are tested in the phase III. We will be able to answer that. We have not yet started the phase III in vitiligo. That's something that is discussed. When we see the different concentrations, then we'll have a question of the size of the tube in some way, and see if it will be easy or less easy to have a price differentiation when we know the result of the phase III in atopic derm. Regarding the commercial aspect, obviously we are seeing this as a very significant opportunity for Incyte. In the case of vitiligo, it is treated by specialists mostly, or entirely, in fact.
The commercial deployment that will be feasible from the financial standpoint are very different in Asia, Europe, and the U.S. The way we look at it is literally three different analyses that we are doing. The program in terms of development is targeted at each of the three, then we have to answer the question of saying, what does make the most sense to maximize this opportunity in Asia, in Europe, and in the U.S.? I can tell you for the U.S. that the number of people that will be required for launching it independently is around 200, and that would include commercial and medical affairs and the team required to do it.
In terms of resources, it's something that is somewhat feasible, and we are going to get an answer, the precise answer to the question, more or less on time, so that when we do the submission next year, when we get the results in atopic dermatitis, we will have a full commercial deployment plan in place. At this stage, we keep everything open in some way, as we are trying to see what would make the most sense. There is obviously a probability of going alone and being able to book the revenues that is higher for the U.S., probably lower for Asia, which is a very complex market in the field of dermatology.
We are still not sure exactly how it's going to end up for Europe, but that would be the picture I could draw today, is a higher probability to go alone in the U.S. or to go and book the sales lower in Asia and still debatable for Europe.
All right. Thanks so much.
Thank you. Our next question today is coming from Evan Seigerman from Credit Suisse for the line is now live.
Hi, all. Thanks for taking the questions. When I look at the F-VASI 50 score, I see that there's not much of a difference between the once daily and twice daily at the 1.5% dose. However, when you look at the 75, you see a much greater separation. Is it practical for patients to apply this twice a day and actually adhere to that longer term to get that 75% resolution? My follow-up is, we have this pretty encouraging data set. What do we actually need to see in a phase III for regulatory approval, and why is this data set not sufficient given the unmet need in vitiligo? Thank you.
Those are great questions. Maybe I can ask Dr. Harris to address the question around what patients would need, comparing the VASI-50 to the VASI-75.
Right, in the practicality of b.i.d. dosing.
Right. Yeah
I think I go through this every week when I see patients in the clinic, and I explain to them the application. I use all topicals at b.i.d dosing. Everybody's using topical steroids and topical calcineurin inhibitors at twice a day. They don't always keep up every day, and I tell them once a day is better than zero, twice a day is better than one. They're usually very happy with that. They're motivated. The majority of my patients actually follow the application at twice a day to get the results that they want.
To your second question regarding the FDA, just maybe could you clarify? I understood it as, was there a thought of submitting this data rather than moving into phase III?
I don't know if it's actually a thought of submitting this data, it's more that it seems that there's such a high unmet need in vitiligo. I guess, what would you need to see in a phase III trial, and would there be any situation where this data set could be used for some sort of accelerated approval?
Sure. I can speak to the regulatory requirements.
Sure. That'd be very helpful
Sure. In general, obviously for a phase III program, you need to show statistical significance, difference between the active arm and the vehicle arm. In addition to that, the FDA typically wants to look at response over time. They want to look at durability of response. Very importantly, the safety of a treatment over time. All of those components need to be included in a submission. Obviously this is a great study, a very robust study, but it was 157 patients, so we are including it and we'll have long-term data, I think we need to expand the patient data set to increase the reliability, as well as look at a larger patient population from a safety perspective.
All right. Thanks so much for the questions. I appreciate it.
Can I add one more comment, just in terms of the practical aspect of applying the cream? What we currently have available, in steroids and Protopic, is that they're in an ointment base in order to get the efficacy that we currently have. It's a very thick ointment, like Vaseline. Patients really, they apply it, they do it, but they don't enjoy it. The biggest complaint about using these treatments that I didn't mention in my slides is how greasy they are. The great thing about the new cream, the ruxolitinib cream, is that it is indeed a cream and not an ointment, and the subjects actually really prefer this. If anything, I think they'll be more willing to apply this twice a day than what we currently have.
All right. Thank you.
Our next question today is coming from Michael Schmidt from Guggenheim Securities. Your line is now live.
Hi, this is Kelsey on for Michael. First, we're just wondering in terms of the F-VASI 50 dose response. It looks interesting in that there isn't really clear separation until week 12. What are your thoughts on that? Follow up, what kind of duration of therapy should we expect should this hit the commercial setting? Thank you.
Sure. I can address the F-VASI. The F-VASI was developed a number of years ago, in the publication there, one of the limitations is that it's a fairly blunt instrument. With the 50% improvement, one of the reasons why we're likely not seeing a large separation between the various dosing arms, especially the 1.5 QD and the BID, is the sensitivity of the 50% improvement versus the sensitivity in the 75% improvement. If you could actually look for a more robust endpoint, you can really clearly see the dose response between the various dosing groups. It's, I think, an effect of the 50% improvement versus the 75% improvement.
I can comment on the duration, if you'd like.
Sure.
The expected duration of therapy. I fully anticipate that most patients will be on a year of therapy in order to achieve the results that they want. There are two options after that in terms of the potential for relapse. Patients currently, with current therapies at least, and we don't know the rate of relapse that will occur with this drug. With the current therapies, patients have a choice of either stopping their therapy once they achieve what they've been seeking to achieve, then waiting for relapse, which may happen a year or two years or later, then restarting the therapy. A lot of patients do that. I also have patients who really never want to see a white spot again, and they use a maintenance therapy of topical application instead of twice per day, twice per week.
I would anticipate that that would be an option here as well. Patients for the rest of their lives could apply a topical just twice per week to maintain their benefit.
The only thing I would add there is that those are all very important clinical endpoints that patients and physicians would like to see. We are trying to integrate as many of those into the phase III program.
Great. Thank you so much.
Thank you. Our next question today is coming from Alethia Young from Cantor Fitzgerald. Your line is now live.
Hi, this is Emma on for Alethia. In the commercial setting, would you expect patients to continue receiving phototherapy or other treatments in addition to RUX cream? If so, I guess how would that factor into pricing and reimbursement discussions?
Maybe, John, you can address the thoughts around combination therapy, then perhaps we can try to address the pricing issue.
Sure. Yeah. The way we use topicals now, as I mentioned in the slides, is we like to use them in combination for patients who have greater than 5% body surface area. If a patient comes into me with less than the 5% body surface area, which is five hands worth of vitiligo all over their body, then we'll start with just topicals. Because it's a practical amount of skin to be able to apply topicals to twice a day. Beyond 5%, it's just too much body surface area. The majority of patients have less than 5%, so we would use topicals alone there. If they have greater than 5% body surface area, we would want to put them on phototherapy as well, because otherwise they'd have to bathe in the cream.
As I mentioned though, we get better responses with current topical and phototherapy than phototherapy alone. I would anticipate using them in combination for the subset of patients that have widespread disease.
For phototherapy
On the pricing, maybe I can say a word. We are in the process of working on how it would be covered in the, at least for the U.S. and Europe, we are in that process. What we know is that phototherapy is
Fairly well reimbursed, and it can be up to $24,000 a year. The question will be for different types of patients, how many of them will be using combination of the two versus single agent with the cream. Overall, the view is that the medical need is well understood. It will be the first approved product for this condition, and we think reimbursement will be achievable, and it will take certainly some evidence to get there. We think it will be well covered. At which level is certainly something we will not discuss till the day of the launch of the product.
Just to add one more thing to that in terms of practicality. When we add phototherapy and patients continue on topicals, they usually are not treating a large body surface area. Patients will often, when they go on phototherapy, they may just treat their face and their hands at that point. They would probably use less cream if they're on phototherapy, and so the total reimbursement might end up being similar.
Great. Thanks.
Thank you. Our next question today is coming from Salveen Richter from Goldman Sachs. Your line is now live.
Yes. Hi. Thank you for taking the question. This is Mariana Tobon for Salveen. I have a quick question. In the study, the median duration of disease was 14 years. Do you think it will be advantageous to start treating earlier in the course of the disease? Also, do you get any additional benefit from some kind of phototherapy or light therapy? I mean, would the great exposure to light have an effect of creating keratinocytes being repurposed? Thank you.
Sure. Maybe Dr. Harris. John, could you handle that?
Yes. Sorry, can you repeat the question again? I had it, then I was ready to go.
Yeah. The median duration that we saw in this study was 14 years.
Oh, right. Yeah.
If we saw patients with lower durations of disease-
Right
What do you think would be the impact, if any, in the phase III study?
Yeah. The good news here, it confirms what we've seen previously, that the duration of disease itself does not indicate the response to treatment. I've had patients with 20-year duration disease respond just as well or better than patients with shorter disease duration. Certainly, there's a huge advantage to starting early. It's not because of the binary response, the treatment will work or not work if it's treated early or late. Really, the amount of body surface area affected directly correlates with how long disease has been present. If you've had disease for 10 years, you're going to have much more body to treat repigment than if you started earlier. Also remember, some parts of the body don't respond to treatment. Those can be protected if started early, and cannot be if started late. There is a clear result, though.
The longer duration of disease, the more likely it is that the hair growing in the spot will also turn white. When that happens, we generally don't see repigmentation. There's that risk. It's more of a binary risk. If you've had disease for 20 years, it's more likely that the hair within your spot will be white. In that case, you won't respond. If you've had disease for 20 years and the hair is still pigmented, there's no problem.
Great. Thank you for that. I can address the second part of that question around the potential for combining light therapy with ruxolitinib cream in the phase III studies. I can say that the phase III programs will be designed as monotherapy, ruxolitinib cream versus vehicle. Obviously we're thinking about future studies beyond the phase III program that will look at a combination of rux cream and light.
Got it. Thank you.
Thank you. Our next question is coming from Matthew Harrison from Morgan Stanley. Your line is now live.
Hi, this is Costa on for Matthew. Can you elaborate a little bit on the dose selection for phase III, and how high the bar is for success in phase III? Thank you.
Yeah. At this time, we're still finalizing the phase III program. We'll obviously have that with the press release, but also in clinicaltrials.gov, the details release then, but at this point, we can't comment on it.
Okay, thanks.
Thank you. Our next question is coming from Carter Gould from UBS. Your line is now live.
Hi. This is Andrea on for Carter. Thanks for the question. How does the phase II data shift how you're thinking about your Inflammation and Autoimmunity portfolio and strategy around business development, both from an in-licensing and out-licensing standpoint?
Yes. I'll take that, and we can discuss it. The way we started this program was really agnostic to any indication. We were really working on the biology, where does it make sense, where there is a medical need. Obviously, vitiligo is a great example of the sort of the strategic aspect of it. When we reach proof of concept, which is what we have done now for both atopic derm and vitiligo, is where the question becomes, do we partner this? Do we find somebody who would be better fitted to make it a success in phase III, and then on the commercial side? As you have seen for atopic derm and vitiligo, we decided to do the phase IIIs ourself.
Now we are at the stage where the same question comes up for the commercial side of could we have benefit from some help or
Do we benefit from licensing out the project? As I said, there is so much value we can see here that we are looking at it over a good period of time, and we are also looking at how we could do it ourselves. For other indications, you could see from the list of the ongoing JAK studies, we will be going through the same process as we see the data coming. We have studies ongoing in ulcerative colitis. We have studies ongoing in hemolytic anemia, in TS, in Sjögren. All of that will be subject to a very specific maximization business development kind of approach. Frankly, there is no rule that applies to all of them. It will be really case by case.
Thank you.
Thank you. Our next question is coming from Peter Lawson from SunTrust Robinson Humphrey. Your line is now live. Mr. Lawson, perhaps your phone is on mute. Please pick up your handset.
Thank you. Dr. Harris, just on the drug, if it's approved, what percentage of your patients would you think about using a topical rux on?
I think, assuming it's FDA-approved treatment, I anticipate that the coverage will push us toward that drug. Right now, if we get denial for coverage, it's because there's no approved drug for vitiligo, and everything's being used off-label. In terms of looking at the efficacy and side effects, I think that it would be very high on our list. If covered, I would anticipate going straight to RUX if the insurance companies didn't require us to go through other drugs first. I think it would be hard for them to do that, because if it's the only FDA-approved drug, it'd be strange for them to say, "Well, you have to try all these off-label things first." We just don't know what the insurance companies are going to say.
The efficacy of this is, in my estimation, much better than any of the topicals that we currently have. The side effects certainly much lower than the other topicals that we have. The side effects really, in my view, for the drug at least, are limited to acne, which was pretty well tolerated. 10%-15% of patients had acne really only as a side effect, and then the remaining had none. I think that the safety profile, the efficacy profile is so good here that if we can get coverage, then it'll be one of the top, if not the first.
Great. Thanks so much.
Thank you. Our next question today is coming from Jay Olson from Oppenheimer & Company. Your line is now live.
Good morning. Congrats on the data, Thank you for taking my questions. I have two of them. At the beginning, you described the quality of life impact, I was wondering if there are other long-term dermatological or systemic morbidities associated with vitiligo if left untreated. Separately, I think you mentioned there are two systemic therapies in development for vitiligo, I was wondering if you could please talk about the pros and cons of a topical treatment for vitiligo versus a systemic therapy. Thank you.
Sure. Go for it. Go ahead. Is there a comment?
No, sorry. Dr. Harris, do you want to take both of those questions first?
Yeah. In terms of the topical versus systemic, I'll take first. I think that it's important to have both. As I mentioned, just the extent of disease really dictates the need for a topical and systemic. Honestly, I think we need both. For small areas of disease, we love the side effect profile of a topical and feel very comfortable with that. A systemic would we really eventually, I think, need for the widespread disease, which is a minority of patients, or patients with rapidly spreading disease and active disease. I really think there's a need and a place for both. Sorry, can someone remind me the first question?
Yeah, the first question was there were quality-of-life measures indicated, what are the other-
Oh, right
morbidities-
Got it
with vitiligo if left untreated?
For patients and their family members with vitiligo, they're at a much higher risk of developing other autoimmune diseases, particularly Hashimoto's thyroiditis. About 15%-20% of vitiligo patients develop Hashimoto's, which is unrelated to the vitiligo. If you treat the vitiligo, we don't necessarily know that that will affect the Hashimoto's, although certainly not a topical, but a systemic might be able to decrease the incidence of that. In addition, what's more directly related to the vitiligo, we think, is hearing loss in patients. There are probably four to six studies that have been done in vitiligo patients looking at hearing loss and showing that there's a greater incidence of hearing loss in vitiligo patients. None of the individual studies was very well done or in a large proportion or well-controlled.
Just the number, the fact that all four or five of them, or six, show that there's some hearing loss is a good indication that that's true. There is some vision loss as well. Again, the data is weak, but there are a couple of studies out there suggesting that long-term vitiligo predisposes you to worse vision as well. There are rare forms of vitiligo that clearly affect vision and hearing. Patients with a syndrome called Vogt-Koyanagi-Harada syndrome actually can become blind from this very severe form of vitiligo. I've only seen one in my career so far, so it's very rare.
Thank you very much.
Thank you. Our next question is coming from Stanley Lee from SEB. Your line is now live.
Hello? How are you doing?
Mr. Lee, your line is not live.
Stanley, can you speak up a little?
Hello? Hello, this is Stanley for Andy Weins. Just to have a quick question regarding this study. For the follow-up study for the 52 weeks and the double-blind data for 28 weeks for the randomization, when do we expect the data, and how do you expect the data? Is it more close to what we have for this study, or just as can I have more info regarding the double-blind study and open-label study? Thank you.
Thanks for that question. We plan to present and share the week 52 data at a future scientific meeting. Unfortunately, I can't comment on the data now, obviously, until we present it publicly. Just you have to wait until the next scientific meeting where we'll be able to share that data with you.
Thank you. We've reached the end of our question and answer session. I'd like to turn the floor back over to Mr. Booth for any further closing comments.
Thank you. Thank you all for your time today and for your questions. We look forward to speaking with you at our second quarter call in a couple of months' time, as well as seeing you at upcoming investor and medical conferences. For now, thank you again for your participation in today's call. Thank you and goodbye.
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.