Dr. Pandya has dedicated his career to the treatment and care of patients with pigmentary disorders, including vitiligo patients. He's also the principal investigator for our povorcitinib vitiligo phase II study, which was presented earlier today. Before we start, just wanted to mention one housekeeping item. This is our safe harbor statement, just to remind everyone that safe harbor rules govern our remarks, and we ask that you review our latest SEC filings for a summary of the risk factors associated with our business. Why are we here? We are very excited to have shared or have had three oral presentations today at the late-breaking session at the American Academy of Dermatology meeting. In addition to those three late-breaking oral presentations, we also presented or had 11 additional...
Excuse me, eight additional abstracts for a total of 11 presentations and abstracts. What we'd like to do is focus today on the oral presentations that were made earlier. We've made significant progress in our pipeline for vitiligo. The slide shows obviously Opzelura, the first and only product approved for repigmentation for vitiligo patients. That's the first of additional products that we're trying to develop for vitiligo patients. We have JAK1 specific oral molecule, povorcitinib, which Dr. Pandya will present and talk about later in the presentation, as well as our newest development product, auremolimab, which is an IL-15 receptor beta monoclonal antibody that targets skin-resident memory T-cells and has the potential to provide a very durable and long-lasting response for patients.
We're obviously very excited by our vitiligo pipeline and very excited to be making history in vitiligo. Here is the agenda. I'll start the presentation with the rehash of the presentations by Dr. John Harris, a chair at University of Massachusetts, who talked about the relapse and maintenance in patients we randomized to ruxolitinib or vehicle in our long-term extension study. I'll also share the presentation done by Dr. David Rosmarin, chair at the University of Indiana, who talked about the continued treatment with ruxolitinib cream in patients from our TRuE-V study to look at the safety and efficacy of continued treatment. I'll turn it over to Dr. Pandya, who will talk about the povorcitinib phase II-B results that he shared earlier today.
He will provide some perspective about the patient treatment, you know, the patients that he treats with vitiligo as well as Opzelura's role in his clinical practice. In the last half hour of the presentation, we'll be joined by Dr. Steven Stein, Incyte's Chief Medical Officer, to answer some questions about our pipeline. Let me start by presenting the data from our long-term extension from our TRuE-V studies done and completed earlier this year and published in The New England Journal of Medicine. This is a schematic just to remind folks of the study design. In the TRuE-V studies, we randomized about 670 patients, adolescents and adults, two-1 with either ruxolitinib or vehicle cream.
At week 52, we shared that data, and at week 52, the patients who had had basically an almost complete response, defined as achieving a facial F-VASI score of 90 or greater, were re-randomized in a blinded fashion to either receive or continue to receive ruxolitinib cream twice a day or vehicle cream. This is important because you know, to look at a randomized withdrawal, to look at durability, you really need to incorporate this blinded re-randomization design feature. For the patients who did not achieve or were not able to achieve a complete response or almost a complete response by week 52, they continued in an open-label fashion with ruxolitinib cream twice daily for an additional 52 weeks.
In terms of the objectives of the two cohorts within the study, in cohort A, we wanted to look at the relapse rate, and we defined the relapse rate as basically losing the baseline facial VASI 75 that they had achieved in the earlier study. We also wanted to see the durability or the duration of response of patients randomized to either vehicle or ruxolitinib cream. In the cohort B, we know that there are some patients who take a little bit longer to repigment their skin. We wanted to see what happens with continued therapy. Can those patients who were not able to achieve a complete response or almost a complete response, were they able to see improvement with continued therapy?
I think another very important objective of this long-term extension study was to really look at the safety with basically two years of continuous ruxolitinib treatment, RUXO cream treatment. Just a reminder in terms of the two patient populations that were randomized in the long-term extension portion, if you take a look at the week 52 in the pink, the patients or those are the patients that were able to achieve a facial VASI 90 or greater. It's about 30% of the patients. All of the other patients, as you can see, many of them did very well. Many of them achieved a facial VASI 75 or greater, facial VASI 50, and even a facial VASI 25. All of those patients continued to receive ruxolitinib cream in an open label fashion.
This is just a summary of some of the important data that was presented by Dr. Harris earlier today. This figure, this slide summarizes the maintenance as defined as patients. The percent of patients who were able to keep a facial VASI 90 response through this long-term treatment period. In the blue line are patients that continued, and again, in a blinded randomized fashion, ruxolitinib cream twice daily. In the green line, you see the patients who were re-randomized to vehicle cream, essentially withdrawn from active treatment. You can see the vast majority of patients who were continued with ruxolitinib cream were able to maintain the facial VASI 90 response for basically another year. That was very encouraging. Surprisingly, 21% of the patients, you withdraw active treatment.
21% of the patients, or more than 21% of the patients were able to maintain their facial VASI 90 response through a whole year. You know, this is very exciting. I think there are patients that can really have a durable response to treatment. When the patients do lose the response, how long does it take? In this slide summarizes the time to relapse. Again, just a reminder, relapse was defined as when patient's response dropped below VASI 75. In the blue line, you see patients who were re-randomized to ruxolitinib cream. You see the vast majority of them are able to keep a facial VASI 75 response or higher.
In the green, you see the patients re-randomized to vehicle. In the time to relapse in the vehicle arm, we see that 29% of the patients who were withdrawn for RUXO cream relapsed. Again, just pointing to the durability response in this patient population that was able to achieve either a complete or almost complete response in pigmentation. Very exciting data. I think great news for patients who stop treatment for one reason or another. Many of them are able to maintain their pigmentation for a very long period of time. For the patients who did lose their respon-response or pigmentation over time, an important question is, well, what happens if they basically restart treatment?
In this slide you see the time to regain at least the facial VASI 75 over time, as well as the time to regain a facial VASI 90 response over time. The one thing I need to point out, though, is many of these patients lost their response later in the year of treatment. Many of them didn't have a lot of time to gain back their repigmentation. For the patients that lost response were basically restarted on ruxolitinib cream, we see that 75% of those patients, basically were able to, you know, regain the facial VASI 75. The median time it took was about 12 weeks.
Again, very, very exciting that majority of them, almost 70% of those patients were able to achieve a facial VASI 90 response. The median time to retreatment, or median time to reachieve that response was 15 weeks. It's really great news for patients. We have many patients who have a durable response. For the patients who do lose their response, they can basically reachieve the high clinical response that they achieve with treatment. They get it back if they restart ruxolitinib cream. Just turning to cohort B. The cohort B, again, was the patients who weren't able to achieve a facial VASI 90 response by week 52. If you take a look at them and follow them over time. In the left, you see the facial VASI 75.
Again, that was the primary efficacy variable, in our pivotal study. If you track those two groups of patients, in the blue are the patients who were initially randomized to active drugs. Ruxolitinib cream 1.5% twice a day. In the green were the patients who were initially randomized to placebo or vehicle cream for six months, or 24 weeks, and then crossed over to active treatment at week 24. There's gonna be a lag in terms of getting treatment, suppressing the immune response, and therefore, seeing the pigmentation, allowing the melanocytes to come back and lay down new pigment into the skin.
For the patients who started off on ruxolitinib cream and weren't able to achieve a facial VASI 90 response at week 52, you see that continued treatment leads to continued improvement. The same goes for the patients initially randomized to vehicle cream. Again, over time, their response, the number of patients who have a better response, who are able to achieve a facial VASI 75 improves with continued treatment. The same goes for the percentage of patients, the proportion of patients who are able to achieve a facial VASI 90. Again, this is really important because the facial VASI 90 really is almost a clear or You know, a full repigmentation response.
You know, we see that patients who are a little bit slower in response with continued therapy can really achieve an outstanding outcome clinically. Really encouraging data from that second cohort because we know that some patients will take a little bit longer. I think physicians can really, if they understand this, can reassure them that with continued therapy, they will continue, or most of them will continue to get a better outcome, better repigmentation over time. In terms of safety, I think this is really critical, is so you have many patients, in fact, most of the patients who were treated continuously for almost two years or for two years with ruxolitinib cream.
What we saw from both cohorts is that there was no change in the safety profile with an additional year of continuous therapy in these patients. Very reassuring from a safety perspective. Again, you know, in the earlier part of the study, the most common side effect that we saw was acne, application site acne, as well as a little bit of application site itching. And we saw a little less of that in the second year of treatment. We didn't really see anything that changed the safety, overall safety profile of ruxolitinib cream.
I think this is very reassuring for patients as well as for treating physicians that two years of therapy, you know, you continue to see a continued improvement in terms of the pigmentation and but really don't see any change in terms of the overall safety. In terms of what we see from this long-term study from the two cohorts in the study, you know, we see that with continued therapy, most patients will see continued repigmentation. That's a very important message for physicians to tell their patients to provide that level of reassurance.
Then the other obviously critical aspect is for patients who are able to achieve response and then for some reason either stop there because they want to take a break or for other reasons, we know that we see that there's a very durable response. Many of these patients will essentially keep their pigmentation for extended period of time. When they do lose their pigmentation, when they restart ruxolitinib cream, we see that most of them are able to regain their pigmentation. Again, very reassuring from a long-term treatment perspective. Again, the last thing is that safety is we don't see any additional liabilities with an additional year of treatment. Very well tolerated.
This is what we saw in the 1st year, and we continue to see that safety pattern in the 2nd year. As I mentioned, you know, Opzelura, this is great data, but we're not done there yet. We have lots of other clinical studies. I just wanted to point out one in particular, that's somewhat relevant to this, to this data set, and it is a phase II study that essentially combines ruxolitinib cream with phototherapy, especially for those patients who are a little bit slower in response. If they want to speed up their repigmentation, we're going to see if phototherapy can boost the melanocyte activity. We know that ruxolitinib cream takes care of the inflammation and the immune response against the melanocytes.
What it doesn't do is boost the melanocytes that have been perhaps senescent or have not been active for many years. We know that phototherapy can boost that response, and so we're studying the combination therapy and should have that data hopefully sometime either at the end of this year or early next year. With that, I would like to turn the present or the podium over to Dr. Pandya.
Thank you, Jim. It's a pleasure for me to be here to really speak about these exciting studies. I've been in practice for 30 years. This is the most exciting time I've ever seen for vitiligo and the vitiligo community. I was a professor at UT Southwestern for 30 years. Internal medicine background, then went into dermatology. After running our cutaneous lymphoma clinic and autoimmune blistering disease clinic, I decided to focus all my time to pigmentary disorders. For the last 13 years, I have been laser-focused only on pigmentary disorders, including hypopigmentation, which is what you're seeing here, and hyperpigmentation. My practice is in Sunnyvale, California, and I only see pigmentary patients by referral. I see quite a few patients, and I can talk later about the numbers, et cetera.
I'm also the president of the Global Vitiligo Foundation and really working with the entire vitiligo community and trying to improve awareness and research for vitiligo. I had the pleasure of being the PI for this for the povorcitinib phase II-B study. You can see some of my other co-authors here, and from the beginning, really consulting with Incyte on the design of this study, and now we're seeing the results of the study. In this study design, we enrolled adults 18- 75 years of age with non-segmental vitiligo. They had to have over 8% total body surface area, and the face had to have more than 0.5%. What does that mean? If you look at the Opzelura study, the criteria were over 3%.
Most vitiligo studies that have been done by industry have been more like 3% or more, and then the F-VASI 0.5%. We already are looking for more difficult-to-treat patients. When you look at the study design, you'll see there were four arms. There was the povorcitinib 45 mg, 75, 15, and placebo. After six months, the primary endpoint was read, then the patients were transitioned to either continuing with 45, if they were on 45 initially, or continuing on 75. The 15-mg group was then transitioned to 75, and the placebo was also transitioned to 75 mg. The primary efficacy was the improvement in the T-VASI in this study.
Patient demographics, these are really important numbers to look at, because this is the first time somebody has tried to look at total VASI improvement in vitiligo. Why is this important? Because improvement in vitiligo is a two-step process. First, you have to remove the inflammatory T-cells, and then you have to stimulate the melanocytes to repigment. Well, you can do that on the face because patients are exposed to sunlight. When you're looking at T-VASI, the vast majority of the lesions are covered by clothing. This was a much higher bar that we had to reach. The age of the patients was older than the previous industry-sponsored studies. It was 50. Vitiligo usually starts in the 20s, between 20 and 30. These were older patients, and older patients tend to be harder to treat.
You can see the majority were white. I was really happy this study enrolled a lot of Hispanics, 19% Hispanics, which is equivalent to the U.S. population of Hispanics. I was also happy to see that 33% were skin types four-six. This is a chronic problem in dermatologic studies, is that we don't have patients with darker skin types that enroll. This was a robust number of patients with skin types four-six. The baseline F-VASI was the highest we've ever seen in any industry-sponsored study for vitiligo. It was 1.3. Just to give you an idea of what that means, the entire face is three or 3.5. 1.3 means a third of your face is white compared to your normal skin. That's a lot.
That is quite noticeable compared to, let's say 0.25 or 0.5. The T-VASI was huge, 25%. The average T-VASI of patients coming into my clinic is 3%. These patients had severe vitiligo involving a large part of their body. Again, a high bar to try to repigment that. Not only do they have a high T-VASI, but these lesions are going to be large, and melanocytes have to migrate. They migrate slowly. Larger lesions take longer to repigment than smaller lesions. The duration of the disease was 19 years. Again, the longest duration of any study that's been done, long duration of disease is harder to treat. These patients have white hairs.
The vitiligo not only destroys the melanocytes in the epidermis, but it destroys the melanocytes at the base of the black hairs, which makes repigmentation harder. The longer you have the disease, the harder it is to treat these patients. I'm sorry. The family history was also high. You can see 28.7. There's some feeling, although the data is not that strong, that patients with family history of vitiligo may have more severe disease than those who don't have a family history. You can see 27% had thyroid disease and previous therapy, topical corticosteroids and 50%, calcineurin inhibitors, 37%, and 45% had had some type of phototherapy. These were not naive patients when it comes to treatment. Here we have the T-VASI results as the outcome measure.
Now, I normally like to talk to my patients about how, what % improvement they're going to have. Like, you're going to have 30% improvement in your lesions over a period of, six months, for example, or 60%. The T-VASI is a high bar because we're asking 50% of the color to come back over the entire body on average. Again, that is a very high bar. And you can see the results here with the three bars, that there was a difference between placebo and the, and the numbers there, at 24 weeks. When you look at the transition, you'll see that the group that was on 15 mg and then transitioned to 75 mg rose up when they go up to 36 weeks.
The other two groups in the green bar and the blue bar did go up as well. There is some variation. When I looked at this, I wondered why the green bars were higher than the blue bars, even though the blue was 75 mg. Some of this may have to do with the fact that it's possible that these were not evenly distributed patients. It may turn out that the patients in the blue bar, the 75 mg group, had more involvement of the body, also had signs of activity, and signs of activity can make your treatment more difficult. We need to look at this data and get a little bit more granular to find out why there's a difference here.
Also, in terms of the cross-hatched red group as they revved up at 75 mg, we're again going to have to look at those patients carefully to see what exactly was the baseline value of their VASI scores and then how much activity they had. You can see that there was clearly a difference compared to placebo, and they continued to improve through week 36 of treatment.
When we look at the F-VASI50, or 50% of your color is back on the average over your entire body by six months, you can see in the green, and I'm having trouble reading that number exactly, but you can see it's around 40 something %. It continued to improve through week 36 of treatment, where you can see it's quite highest in both the 75 mg group and the 45 mg group. The F-VASI75 seems to be one of the most commonly looked at outcome measures now. Studies have shown that patients believe that 75%-80% repigmentation is what they consider clinically relevant on their face.
We haven't asked patients for the body in larger studies, and we're working on that in the Global Vitiligo Foundation to find out what's relevant for them in terms of clinical improvement for the body. But suffice it to say, F-VASI75 seems to be a good goal to try to get to. And you can see that there was a significant number compared to placebo that did achieve that F-VASI75. This is a slow process. These patients were not being treated with phototherapy. They were getting just regular sunlight. They were not asked to sunbathe as they are in other countries that the way vitiligo is treated. And yet, we did see that improvement and that continued on through week 36 of treatment. Here's some patient photographs.
You can see the patient on the left. She had 44% improvement in her F-VASI at 24 weeks, and then she was switched to the 75 mg. She was on 15 mg. Now at 75 mg at week 36, 12 weeks later, she zoomed up to 85% improvement in her F-VASI. Then on the extremity, you see the patient on the right. She improved by 31.8%, and then she zoomed up to 64.8%. In these pictures, you can see the perifollicular repigmentation. This patient was fortunate that she had hair follicles with black hairs. Around those black hairs, the melanocytes migrated up the lateral root sheath and then filled in the skin. You can see the hundreds of dots on her skin as a result of those melanocytes migrating out of those follicles.
That takes time. That takes months and months and months of time. Even if all the T- cells are removed from the skin, it requires time for those melanocytes to respond, and they will do so more with light exposure. She was just getting incidental sun exposure to extremity. It was generally well-tolerated. No serious adverse events were considered related to treatment. No new safety signals were observed. I'll just point out acne. Acne is something that we see in JAK inhibitors, and you can see the 75 mg had 14% acne, 7% I'm sorry. Yeah, 75, 14, and then 45 mg, it was 7%. There was a difference there in those numbers. That seemed to be the most important.
You can see the fatigue was in 14% in the 75 mg group and 7% in the 45 mg group. This was the first report of povorcitinib in patients with extensive, and I just wanted to underline extensive, severe vitiligo. It was associated with substantial repigmentation with in patients with this extensive vitiligo after 24 weeks. We saw continued improvement through 36 weeks. I'm looking forward to seeing the follow-up data, the 52-week data to see how these patients improve. It was generally well-tolerated with a good safety profile and a few grade greater than three of serious adverse events.
I'm gonna go on and give you kind of a general overview of vitiligo and kind of the big picture and give you a little bit of information about my practice and how I treat these patients and what I see. Again, I have this clinic in California, specialty in vitiligo and pigmentary disorders. I see about 80 vitiligo patients per month, and of those, 80 patients, about 20 are new and 60 are follow-ups. You can see the Palo Alto Medical Foundation, where we have the pigmentary disorder clinic. At least 50% have facial vitiligo. Almost all have visible lesions. That's why they come to see me. Very few come for vitiligo that's exclusively in areas covered with clothing.
A 100% of my patients receive treatment, at least some type of treatment. I'm very active in the vitiligo community, again, president of the GVF, also an organizer of the Vitiligo International Symposium. Vitiligo is bad enough in the United States, but it's a disaster in other countries. When you look at quality-of-life studies that compare, Saudi Arabia, the Middle East, India have the highest effects on quality of life. A lot of that has to do with culture. A lot of that has to do with the fact that this was thought to be a curse going back thousands of years. It's in the Ebers Papyrus in Egypt. It's in the Rig Veda in the Hindu writings. And it's in Leviticus chapter 13.
Vitiligo goes back a long way, and there is a stigma to it. That's why our international symposium is well-attended by doctors from around the world. We just had it in Bangalore. Our next one will be in Cairo. I'm also an editor for my vitiligo team, which has 10,000 followers online on social media that learn about vitiligo, and our board of directors supplies this information. I'm quite a bit involved in the area of vitiligo. I have a very busy practice. We have right now about a five-month waiting list if you want to see me as a new patient with vitiligo. That's very distressing to patients because as you can see, in three months you can have relapses, you can have worsening of your vitiligo.
Many of them have told me, "Doctor, five months ago when I made my appointment, I just had a little bit, but look at me now, it's gotten worse on my face because it took that long to get in to see you." There is a problem with not having enough doctors that understand vitiligo and actually have seen a patient from zero- 12 months and watch that patient get better with serial photographs. That motivates a doctor, that motivates the patient. Most dermatologists do not do that. That's something that I hope Incyte can partner with us so that we can teach doctors how to properly take care of vitiligo so that we can have more, more positive re-results.
Unfortunately, because of my time constraints, I just can't see any more than I'm seeing right now. You know what vitiligo is, and you know that what it does to people. What you see is on the surface, but it really affects the patients psychologically quite a bit. You can see anxiety, depression, suicidal ideation. There's a famous young man named David who all of us who are vitiligo specialists have heard of him because he's been presented in various meetings. He had vitiligo on his face. He was African American, and he took his life because he just could not live with this stain and this depigmentation and everybody staring at him and having to explain it to hundreds of people.
Just when he walks down the street, everybody's asking him about it and looking at him, et cetera, et cetera. We have had suicides from that. Certainly a high incidence of anxiety and depression, body dysmorphic disorder. It does impact careers, those who are seeking jobs. We have shut-ins, a lot of shut-ins who will not go out because of their vitiligo. Some of our individuals in the vitiligo community will visit people's houses to talk to people with vitiligo to help them try to get more confidence in getting out of their, out of their house. The economic burden is definitely significant. The multiple doctor visits, these patients are coming into my office three times a week for a whole year.
If I'm lucky enough to get them a home unit, they can be treated at home. They still have to see me every three months. The medication cost is definitely there. Lost time at work that they have to explain coming into my office, this economic burden. Also lost time at school for the kids that I see with vitiligo. We did a study in which we looked at the psychosocial comorbidities. We found many items, and these were hundreds and hundreds of patients that we did look at in this publication. You can see the depressive disorder, behavioral impairment, emotional impairment, suicidality, anxiety-related disorders, adjustment, just many different disorders that have been associated with vitiligo and multiple studies with its effect on quality of life.
The problem is that vitiligo is undertreated. The standard story I get is, "Doctor, I got this 10 years ago. I went in to see my dermatologist. They said, 'Oh, you have vitiligo. There's not much you can do for it. Here's a cream. It's probably not gonna work, but you can try it.' I used it for two weeks, I stopped, and my vitiligo get worse." I have heard that exact scenario hundreds of times, that story. Few patients are being treated correctly. There's lack of approved therapies. Now we finally have our first FDA-approved treatment. Even clinical data, we don't have as robust clinical data as what Jim just showed for corticosteroids or tacrolimus, even though these have been around for decades. Just these studies were never done. Vitiligo is underfunded. It's under-researched.
The lack of compliance with treatment, and that's a big problem, and that makes me wonder about the slides that Jim showed. If you have a person who's already repigmented 90% of their face and you tell them, "Keep putting this cream on twice a day for 365 more days," you know your compliance is potentially going to be lost. I think that we should be looking at maintenance treatments, for example, perhaps twice a week or three times a week to see if they can maintain their treatment 'cause compliance is a big problem with topicals. I'm looking forward to povorcitinib once-a-day pill, which patients really do prefer over having to put something on twice a day.
The burden with cost, we've already talked about, I've already talked about the fact that healthcare practitioners are really not that familiar with it. When we think about how many people have vitiligo, there's about two million-three million people. We think about 0.8% of the population, less than 200,000 are being treated. In fact, we are about to publish a study that shows that 40% of people with vitiligo are not even diagnosed. The way we figured that out is we sent out an online survey, and we asked people to answer some questions, and they sent in some pictures. We were able to diagnose vitiligo by pictures in patients who had never seen a doctor for those white spots.
40%, especially in the Latino and the African American community, who undergo the greatest healthcare disparities in this country. There is a large number of people out there who are underserved and are not utilizing healthcare. I think that Opzelura can actually change this lack of treatment because I have had patients just this last week, two of them came in, and I said, "Okay, can you tell me why you came in today?" They go, "Oh, I saw something on TV about this new cream," or, "I heard about something, my relative. I heard about Opzelura, and I'm here because I want to get on that. I'd like to hear more about that because I've never heard of any FDA treatment for vitiligo." I think that's going to change the paradigm.
It's going to bring thousands of patients into dermatology office because they're hearing about Opzelura, and they have this desire to treat. I think that doctors will be more willing to treat because doctors are skeptical about tacrolimus. They're kind of fearful of corticosteroids. They don't think that low-potency corticosteroids work, especially on the face, especially on the body. On the face, they are reluctant to use high-potency corticosteroids. I personally don't think tacrolimus works from the neck down. I did a study in which we treated half the body with Vaseline, half the body with tacrolimus, and after 12 weeks, we saw the same improvement with phototherapy. We don't have robust data with those.
Now we have with Opzelura this good, robust data that actually went past the bar of the rigorous FDA standards of what's needed to get a medication approved. Now, each patient is unique. There are different drivers of patients seeking treatment. What will cause a patient to seek treatment? Here's the story I've heard many, many times. "Doctor, I got this on my knees when I was young. I just learned to wear capri pants. I just learned to hide it. And it's been like that for 20, 25 years. But I got this new job. I got, you know, a lot of stress. And look, now it's on my chin and my forehead. And I am scared to death that it's now gonna be on my face. It's never been on my face.
I want some treatment." I have heard that countless times. It's the location and also the extent. "It was just on my fingers, doctor. Now it's in the back of my hands, and now people can see it. I was able to hide it on my fingertips, but now people can see it." Extent is definitely an issue and location of the lesions. The number of years with vitiligo. When you look at the actual quality of life, you find that people who got it when they were five years old have a better quality of life as adults than people who got it as adults. They tend to have higher stress from the vitiligo and lower quality of life. Access to a vitiligo treatment center is a big problem.
Right now, we only have maybe nine treatment centers of people who publish on this and see a lot of vitiligo patients, and we need a lot more. One of our goals with the Global Vitiligo Foundation, in conjunction with support from Incyte, is to have more webinars and more educational events around the country for dermatologists, so they can learn a state-of-the-art treatment of vitiligo. Insurance coverage, of course, is also an issue. These patients have difficulty getting phototherapy coverage, excimer light coverage. Opzelura, surprisingly, we've been able to get good insurance coverage for Opzelura in the majority of our carriers, and especially now that Incyte has given us a very easy way to get our prior authorizations authorized. The majority of my patients are able to get it.
I would say about 75% of my patients are able to get Opzelura. 25% are not able to get it, and most of them are the Medicare patients. Insurance coverage is also ways of it's a factor in terms of those who come in for treatment. In terms of what percentage of patients have success with treatment and adhere to treatment, it really depends on the areas that are being treated. If they have vitiligo on their face and they still have black hairs in the areas of vitiligo, 90+% of those patients are going to respond to treatment. The hands don't respond as well. The feet don't respond as well. I think that the vast majority are going to have response, and Opzelura would be perfect for those patients. All right.
In terms of the treatment plan, factors to think about, well, do they have stable vitiligo? Do we need to stabilize the vitiligo? The patients you see there on the hand, you notice that there's light brown areas as well as normal-colored areas, and then there are white areas. That's called trichrome vitiligo or three-color vitiligo. If I biopsy those areas with light brown skin, I would see hundreds of T cells in the skin killing melanocytes. This is active disease. This patient has an infiltrate of T cells as opposed to someone who has white spots that have not changed for many years. If they have unstable disease, I'm going to treat with oral steroids. I hope I can get something like povorcitinib in the future, something that's more aggressive.
Right now I'll treat with oral steroids, topical Opzelura, and phototherapy. I will pull out all the stops and treat this patient with all of that right now. Unstable vitiligo. Also in terms of what their goals are. Every patient is unique with their own hopes and fears and goals, and that's how I customize my treatment. If patient says, "If I can't get 100% back, doctor, then I don't want treatment," then we just stop right there. We have that conversation. Hardly anyone says that. They say, "If I can just get some back, I can feel like I'm more confident, and if I can see the color coming back, then I will stick to continuing my treatment, and I wanna go until I plateau." That's what the majority of patients will say.
Some of them have had bad past experiences with treatments, and that's something I have to kind of overcome. The nice thing about Opzelura is that even if they've had bad experience with dermatologists, when they see that commercial on TV, they say, "Oh, there's something new." Then they'll go online, they'll Google vitiligo specialist, they'll find me, and then they'll come in for that. They also need to know percentages. Every single patient I say, "Look, if you follow this treatment plan, you are over your entire body, you're gonna be 25% better in three months, 50% better in six months, and 75% better in nine months." Those are real numbers from multiple studies as well as my experience.
It'll be higher on the face, less on the hands, and when I explain that to patients, then they comply, and then they understand that they shouldn't call my office in six weeks wondering why they're not much better. It's a slow process. You really need to set those expectations. Then the logistics and the cost. Where do you live? Do you live close to my office? I'm the phototherapy director for the entire Bay Area for Sutter Health, and so we have 8 centers where they can get phototherapy around the Bay Area. That's one thing. The other thing is, can you afford a home unit? I have 600 patients with home units, so can we get you a home unit? Lots of things when it comes to logistics and how they're going to get phototherapy combined with their, with their treatment.
Of course, their ability to afford their treatment. Their age. Some of my elderly patients think that it's too much hassle to do all this, and they just wanna treat their face, and they don't wanna treat their body. They just wanna maintain their treatment. Some of my younger patients want to keep going full board until they get maximum improvement. Cultural background is huge. I work in the heart of Silicon Valley. I've got Apple to my right in Cupertino. I've got Google to my left in Mountain View. We have a huge number of Asian patients in my practice who are all into in the IT field. When you come from a Asian background, you have much higher stakes when it comes to marriage, for example.
If you have vitiligo, and your parents are talking to the parents of the potential mate, they might call off the wedding because you have vitiligo, and they don't want vitiligo in the family. No longer do Indians and people from all Asia feel that vitiligo is leprosy. They understand that vitiligo and leprosy are different. Although in ancient times it was not there. In fact, the name for vitiligo was venkusum, which means white leprosy in Sanskrit. We know now, and all people in South Asia know it's not leprosy. However, they know it's genetic. If their family does not have vitiligo, they will not bring a bride or groom into their family with vitiligo. This causes a tremendous amount of stress to the family.
Not only that, the 14-year-old brother of the woman who's looking to get married, if he has vitiligo, she won't get married because once they find out her brother has vitiligo, they're afraid those genes will come into their family. That 14-year-old young man has a tremendous amount of stress because of the sadness he's brought to his family. These are the stories I hear. These are the stories that a lot of dermatologists don't know when they see this desperate person coming with 1 single spot of vitiligo on each hand wondering, "Why is this person making such a big deal about their vitiligo?" They don't understand what's going on in India, what's going on with marriage, what's going on with parents. You have to really scratch the surface and understand that. Culture, ethnicity, those things are super important.
I'm amazed at how much support there is in the African American culture. African Americans can handle vitiligo in such a noble way with so much support that I've just been blown away how they go through life with vitiligo and enable to get support from their community. When it comes to vitiligo, there are three pillars for effective treatment. If you pay attention to these three pillars, you can get effective treatment. Again, there is a nuance in vitiligo treatment, and I hope that all 15,000 dermatologists can learn this now that we have these medications. First, you have to reduce the triggers. We avoid trauma, and we also give antioxidants to reduce the triggers. We reduce the immune attack on the skin.
We give tacrolimus, pimecrolimus, topical steroids. Now Opzelura is my go-to cream. If it's covered by insurance and the patients can get it, there's just no downside to Opzelura. It's well-tolerated. Patients like it. It goes on well. It's not an ointment like tacrolimus. You can put it on your eyelids. You can put it on your around your mouth. You can put it on the genitals. It's just an easy medication to use. Then phototherapy comes in after three months. It takes about 10-12 weeks for phototherapy to remove those T-cells in the skin. I also, in the beginning at least, certainly for the first three months, have to give phototherapy, and that stimulates melanocytes and melanin production. Afamelanotide is another drug that can be used, it's not available in the United States.
Sometimes we do skin grafting and cellular grafting. These three pillars of therapy are important in all of my patients and actually go through all three pillars with every single patient that I see. Now with Opzelura, you know, we have this first FDA treatment. It's got this impressive efficacy when you looked at the TRuE-V studies. I use it as my number one choice now. 90% of my patients, I think, qualify for Opzelura. I don't use it in small children. It's not approved for children less than the age of 12, and I see many children with vitiligo. I don't use it for patients with extensive vitiligo because it's only approved for more than 10% or up to 10% of body surface area.
I tend to avoid it in those individuals. Otherwise, I tend to use it in all my patients, and it's working well for me. Setting those expectations is important. The repigmentation takes time. This is a great patient for me to illustrate that. This is my patient. She was in the phase II study, and trust is super important. How do you see a patient every month in a clinical trial, and they're not getting better, and she continues to apply a cream twice a day? That's hard, and it requires trust between her and me. She trusted me. I knew her. I knew her husband. I developed a relationship with them. She came in month after month after month and did not get better.
In fact, if you look at that second picture, she's actually a little bit worse. I didn't know she was on placebo. She didn't know she was on placebo. This is how trials are done. I was promising her at month four, month five that, "Don't worry. At month six, I know you're going to get the active drug. Don't worry. We know. Or I don't know if you're on the active drug right now. It takes time for T-cells to get cleared out. It takes time for melanocytes. I don't know if you're on." Look what happened to her six months later. She repigmented dramatically. You can see like 90+%. She was absolutely delighted, and so was her husband, to see that repigmentation. She understood about the slow migration of melanocytes. Fortunately, she went on.
Incyte was able to provide phototherapy for these patients at home. She got a home unit. She 100% repigmented her face and her neck. She came to our celebration of World Vitiligo Day. The day I saw her on the dance floor was one of my wonderful days. I got to celebrate with her as she was so happy that she got her color back because she said, "Doctor, I'm Black, and this is part of me. This color is actually how I define myself." It was very important for her own sense of her own sense of self. I just wanted to tell you that story because she was one of my memorable patients.
Again, the speed of repigmentation depends on the area of the body, age, length of diagnosis, and if they have black hairs. When I first saw her, I pulled out my dermatoscope, and I noticed all her tiny hairs on her forehead, her temples, her cheeks, even her chin were black. We have thousands of tiny hairs called vellus hairs on the face. I knew she had the potential of improving. If all of them were white, I would still treat her exactly the same, but I wouldn't expect 90% repigmentation. It would be a lot less. We have to look at these things before we start. The percent of repigmentation definitely varies, and compliance is important. I explain this to patients who are complaining about applying it twice a day.
Doctor, I'm only putting it on once a day." I said, "Well, in the phase II study, the once-a-day did improve, but the twice-a-day improved more. If you want to have that delta, if you want to have that, you know, 12%-14% improvement, you should do it twice a day." The majority of patients are likely to respond to Opzelura. You can see the F-VASI responses after 52 weeks. You can see the F-VASI 90, 75, 50, and 25. Then, Jim's already talked about that they continue to improve. I always talk about a plateau with phototherapy because after about nine months of phototherapy, one plateaus. It's very exciting for me to see there is no plateau. We have not hit the plateau quite yet with Opzelura.
I'm looking forward to seeing what happens to patients who are treated even longer. They can respond to longer treatment. If the F-VASI is not reached at what they want, F-VASI 90, we just keep going. What happens if F-VASI 25 is not reached at week 24? You could add phototherapy to provide a boost. Actually, I would do that at week 12. If a patient insists that they do not wanna do phototherapy and they just wanna get their sunlight from walking outside, and at week 12, we don't have even an F-VASI 25% improvement, I am going to insist that they figure out a way to do phototherapy. One way or the other, we'll try to figure out a way to do it to get that phototherapy.
In terms of follow-up, I see them at baseline, and I see them every three months. My nurse takes a picture of their vitiligo lesions, and when they come back, I pull up the lesion on the screen with them, and I show them, and I look to see if there's 25% improvement. The only way you're gonna be able to detect 25% improvement is with photographs. Here you see more pictures, continued improvement at 104 weeks. If a patient comes in at week 52, he's going to be happy, but many times he's forgotten what he looked like initially. I can't tell you how many times that I'll see a patient, like in week 52, and he'll be looking at the glass as half empty.
He'll say, "Look, doctor, I still have this." I said, "You know what? Let's pull up your baseline picture." When I pull up their baseline picture, they said, "Did I look like that?" I said, "Yeah." He goes, "I forgot how bad I was. I'm glad I'm better." That motivates him to continue. You can see at week 104, he continued to improve with 83% improvement in this picture. So you have multiple possibilities for maintenance once the F-VASI 90 is achieved. What would I do if F-VASI 90 is achieved? Well, I have a conversation with my patient at that point.
I'll say, "There's a possibility you could get F-VASI 100 if you are willing to put this on twice a day." You know, I'll say, "Look, you have a choice." Some patients say, "No, this is enough. I'm tired of putting this on twice a day, so I'm just going to stop." In that situation, you have about, as Jim said, about a 30% chance of losing a substantial amount of your color after one year. If you don't wanna do that, you should stay on the Opzelura. The other option is something that hasn't been studied yet, that's twice a week. Excuse me. Twice a week Opzelura.
The reason I say that is because there was a study in which they used tacrolimus twice a week, and they found that if you use tacrolimus twice a week after you had repigmented, you only have a 10% chance of relapse, whereas if you don't use anything, you have a 40% chance of relapse. I tell my patients, on Monday and Friday, apply the cream. They're willing to do that twice a week. That's something that they like. I will be excited to see if Opzelura will be able to match tacrolimus. I see no reason why it would not. That's kind of what I do in terms of whether we're gonna stay on Opzelura continuously, stop it or give it twice a week.
The other good thing about the study that Jim talked about is that I tell my patients, "If you do have a relapse, don't worry. We can repigment you." I say that even currently with my phototherapy patients, that you can repigment. I tell them, "I will never let you get back to the way you were when you first saw me." That statement right there is such a relief to my patients when I tell them that. I'm gonna work with you, and I'll never let you get back to the way you were when you first saw me. How has it changed my clinical practice? Well, like I said, there's a lot of patient excitement. People are coming in.
I actually am very happy that Incyte is putting these commercials, the one with Morgan Freeman, the one with Pearl Grimes on TV and these announcements because a lot of people really didn't either know about vitiligo or they thought there was no treatment. For me to know there's 40% people out there who are not even coming to see a dermatologist, I want them in my office. I want them in dermatology offices. This is what Incyte has helped us do. They're excited. Motivation is high. They are proactively scheduling appointments to ask about Opzelura. Like I said, just this week, I had to say that. That's why they came to see me. I got this four-five-month backlog. What does this mean for physicians? They need to provide patients this education like I've just told you.
The way I've described it to you, I think if every dermatologist does it that way, we would have better compliance. We'd have better results. Physicians, dermatologists would be more motivated. They can now offer this FDA-approved therapy backed by strong clinical data. Most patients should be able to access Opzelura through their insurance plan. I am very fortunate in that I have a wonderful Incyte representative in my practice in Sunnyvale. We've When Opzelura came out, she came in and told us exactly what to do. My colleagues, many of them are still trying to figure it out. I really asked them to talk to their representative. She told us how to find a pharmacy that'll do our prior authorizations.
When I have a patient, my MA, who is very good, she just copies my note, sends it to them. That pharmacy does the prior authorizations. They get it through insurance. If they can't, they go through the patient assistance program. Everything is automatic. Like I said, 75% of my patients are able to get it paid for, and they only have a $10 or $20 copay. Which is just fantastic. Every dermatologist should have that type of service, and I hope they do. For me, it tends to be fairly easy, but I'm very fortunate in the support that I've received from Incyte as well as my staff.
The most difficult patients are the ones with Medicare, and I hope that Incyte and the Global Vitiligo Foundation can work on it so our Medicare patients can get a better deal and get access to this, to this medication. I think it's a game changer. Accutane was a game changer with acne, with the prolonged remission, and for deep, painful acne. When you look at patients with psoriasis, the biologics that have been available have been a game changer. Dupixent is unbelievable. I just cannot believe what Dupixent does to atopic dermatitis patients that I've seen for 30 years, how it can clear patients. Now with Opzelura, we have some of these amazing results, and it's FDA-approved, and we have really good, robust data that it works.
I think this is going to be a real breakthrough and a, and a game changer for us for vitiligo. In terms of other exciting developments, I can't wait to see the results of the light therapy at Opzelura. Two of these patients are mine, so they're getting their light box this week. They did not have 25% improvement at week 12, so they qualified to get the light box. They're getting the light box, a panel, at their house this week, and then we'll be starting phototherapy. I expect them to repigment very well with that combination. The povorcitinib and other oral JAK inhibitors targets that inflammation, and that's going to be great for these patients with extensive vitiligo, more than 10%, which are a lot of individuals.
The IL-15 receptor antibody, which targets that, the auremolimab, I can barely say that, but to eliminate these cells to give us durable remission, I'm also excited about that because vitiligo does indeed come back in the same place that it was in the beginning. If this antibody will re-remove that, then I'm excited about that too.
Great. No, thank you so much, Dr. Pandya. That was wonderful. Really appreciate the, the patient perspective, how you treat the patients. It's a reminder to us at Incyte of how important it was for us to develop Opzelura, but also the commitment that we have to develop additional treatments for your vitiligo patients. With that's the end of the presentation portion of our segment. I'd like to ask Dr. Steven Stein, Incyte Chief Medical Officer, to join us on the stage. While he does that, I just wanna make sure that a microphone is available to the participants in the audience. What we'll do is start with the participants in the audience with questions.
Hey, Rob Andrew here from William Blair on for Matt Phipps's team. You know, it's been highlighted a few times in the conference and here tonight as well that exposure to sunlight is pretty important here. You know, I'm from the north of England, Fitzpatrick 1. If I see the sun outside, I'm probably not going outside. You know, I'm just kind of wondering, given the lack of an obvious dose response for povorcitinib, you know, is there any evidence that geographical differences or behavioral differences, seasonal differences in the clinical trials actually lead to a different response just given the impact that might have on sun exposure?
Yeah, maybe I can address that or at least try to tackle that. We do have indirect evidence that sunlight makes a difference in terms of responses that we saw in the clinical trials. The reason for that is when you take a look at the delta, the difference between the facial VASI response and the total body response, you know, we take a look at the body, the trunk, and those areas are definitely much slower to repigment than the face. Absolutely. If there's a person who's not going outside, their facial VASI score is not going to improve as fast.
In fact, I remember Dr. David Rosmarin telling us there was a patient, one of his patients who had residual hypopigmentation on his forehead, and he just reminded him, "Why don't you take your hat off?" He took his hat off, and that area repigmented. We know that whether it's natural or ambient light versus a phototherapy, that does impact the rate of repigmentation.
Right. I would say that, I treated my patients in Texas, and they were walking outside in Dallas and Austin and those areas. As I was talking to my colleagues in Boston, you know, just talking about the study, they were not seeing as great responses as I was in Texas because the amount of UV, you know, exposure, sunlight exposure was so much more.
Maybe just Jim and Dr. Pandya, any comments on the second part of that question, the dose or seemingly lack of dose response in this phase II study? Any thoughts on perhaps the biology behind that?
Maybe I can start with a more of a biological perspective, and that is we know that povorcitinib has very good tissue penetration. What we don't know is how much of it is needed or needs to get into the skin to block the interferon-γ as well as the IL-15. It was, you know, it looks like 45 and 75 had similar responses from a VASI perspective. Because of the numbers are modest, that could have been just due to random change. What appears, you know, for us is that the 45 and 75 look like a similar dose in terms of the response that you're able to achieve.
The 15 definitely, I think you see some separation. We're gonna share some translational data later this year that supports that, the 45 and 75 probably are the, you know, strong enough to get the repigmentation and probably you need more than 15 mg per day.
What I would say is the T-VASI and the F-VASI have error in terms of measuring by the investigator. It's not an exact science. It's more difficult, in my opinion, than doing the PASI or the EASI or the VASI score, and I've done all of those. Reason being is that not only do you measure the body surface area, but you have to multiply it by the amount of deep amount of pigmentation within the lesion. It's hard enough for me to do who's seen thousands of patients, but it's hard to teach that to an investigator. When we look at these bars, we think that, you know, there's sometimes quite a difference, but there's actually a range of error when it comes to doing that. The smallest detectable change.
Ideally, what we should have is we should have a camera that takes a picture of the whole human body and then just tells us how many centimeters squared of vitiligo they have at baseline and at 24 weeks. The FDA doesn't allow that. The FDA sees the VASI kind of as the gold standard, and so we have to use that. Studies have shown that there is a error, a significant error between raters, even the same rater looking at the patient over time, or twice, for example, intra-rater reliability can be an issue.
Hi, this is Divya Rao, from TD Cowen on for Mark. Just looking at the povorcitinib data, you know, it looks very promising. I guess if it's approved, do you anticipate you'll keep these patients on povorcitinib chronically, or maybe just like a bridge, and use Opzelura as more of a for maintenance therapy for these patients?
I know that, if I stop the medication that's suppressing the T cell from infiltrating the epidermis and killing melanocytes, I feel like they will slowly come back. I'm not removing these T cells from the bone marrow, from the spleen, you know, from the lymph nodes. They're there. We don't have a medication that zaps them permanently. What'll happen is eventually over time, perhaps through trauma, perhaps through sun exposure, whatever it stimulates interferon-γ, it'll come back. I think that, with povorcitinib, let's say that I do get 90% repigmentation or substantial amount, and now they have a very small amount of vitiligo, then you could just switch to Opzelura. Absolutely.
The problem is that if they, for example, had 30% to begin with and now they only have 5%, if they apply Opzelura to that 5%, the rest is not being treated, and the T cells tend to come back to, into the same places where they used to be before. With the new IL-15 receptor antibody, if we can remove those resident memory T cells, then hopefully we'll have a durable remission, so they won't get it back. Those are some of the thoughts that we have.
Any additional questions from the room? Could you use the microphone? Thank you.
Yeah. You mentioned that about 25% of the patients, get a rejection from the payers and are usually Medicare. Is that because Medicare does not cover it, or what are the reasons for denial?
I wish, I wish I knew. I guess Medicare Part D doesn't really cover it. I don't know if...
I think maybe folks at Incyte.
Yeah. Barry Flannelly, who's head of the U.S. commercial organization, will respond.
Yeah. So far, Medicare does not cover it for a variety of reasons. Just it's a little. For example, it doesn't cover Dupixent either. It's just one of those things. We're definitely working on it, and we'll do it particularly for vitiligo. In the AD patient population, we don't have as many patients on Medicare that are using the drug. For vitiligo, even in the study, in TRuE-V studies, I think it was about 10% were over 65. It's something that we're working on, but it takes a little longer than the commercial payers. Great. Okay. If there are no more questions in the room, operator, if you could open up the line for questions for folks who are on the line.
Thank you. We will conduct a question and answer session. If you would like to ask a question, please press star one on your telephone keypad. To remove your question, you can press star two. One moment while we poll for our first question. Our first question comes from Srikripa Devarakonda with Truist Securities. Please proceed.
Thank you so much for taking my question, congrats on all the data. Jim, Steven, My first question is for you guys. It's about the patients in the withdrawal cohort that were then retreated. It looks like 75% of the patients who relapsed due to withdrawal were able to achieve F-VASI75 and about 69, I think, of those who achieved F-VASI 90. Can you maybe talk about what might be happening with the patients that did not respond? Do you think this means that people, patients are more likely to stay on treatment and would not want drug holidays? I know you can't repigment. Dr. Pandya, a question for you. You mentioned that it's typically patients who have facial lesions that come for treatment.
How many vitiligo patients do you think fall into that category? With Opzelura and if povorcitinib were to be approved, do you think that might change the way patients seek treatment? Thank you.
Well, you want me to take the first part? Thank you for the question. What likely has happened is that when someone lost the response out in month 20 or 24 and then restart treatment, they really don't weigh on this. We ended the study at year two, so week 104. Many of those patients will likely have been able to regain their facial F-VASI75 and even their facial F-VASI 90 if we had kept the study going longer. I think there's nothing to believe that we haven't seen anything where patients will develop tachyphylaxis, they don't respond to retreatment.
Based on that we saw in the retreatment arm, I think that was just a factor of basically stopping the study at year two.
Yeah. I personally think that the vast majority of people who we think have tachyphylaxis are just non-compliant. That's why they're not achieving the F-VASI 90. I'm sorry, could you repeat your second question?
I had a question for Dr. Pandya about patients. He said patients typically who have facial lesions are the ones who come for treatment. With, you know, you have Opzelura approved, and, you know, if povorcitinib also were to be approved, like if they have options, wouldn't patients who don't have facial lesions also come in for treatment?
Oh, I see.
in the other parts
Yes.
-of the body. What % of patients are the ones who only have facial lesions?
Oh, well, first of all, I think at least 50% of my patients have facial lesions. In terms of what percent only have facial lesions, it's hard for me to kind of estimate. It may be 10%-20%, something like that would have face, ear, face and ear lesions only. Almost everybody has a lesion somewhere else when they have facial lesions. Yeah, they're coming in for facial lesions, and the Opzelura is perfect for them.
If you're asking about povorcitinib and what I would do for that in the future, if they have more than 10% body surface area, and especially if they're getting more active disease and I'm afraid that they're going to go to 12%, 15%, 20%, then povorcitinib certainly makes sense for them in patients with active disease. You could even combine it where you perhaps even get an even better result if you use Opzelura on the face and povorcitinib so that you could treat both the body and the face. There's lots of different options that we could have in the future. There aren't that many people who have both face lesions and the body lesions that want to get treated except for those who have it on their hands.
I have quite a few patients who have it on their hands and feet, especially in certain cultures where their feet are showing a lot in various social settings. Those patients do come in, and they want to get treated on their hands and feet. Those will be the tougher patients. Opzelura, nothing actually works on the hands and feet as well as it works on the face. In those patients, we will be treating aggressively with phototherapy from the beginning, along with topicals, and then perhaps even grafting those patients later on.
Got it. Thank you so much.
Mm-hmm.
Our next question comes from Jessica Fye with JP Morgan. Please proceed.
Hey, guys. Good evening. Thanks so much for taking my questions. Starting on povorcitinib, following up on, I think, the first question, just wanna clarify. I'm sure you guys have gone back and looked at the baseline characteristics for the different dose arms in that trial and what might explain the unusual dose response on P-VASI 50 or even F-VASI50. Are you saying you think different light exposure explains that unusual dose response? Are you just suggesting that's a possibility but not something you've specifically established? That's the first question.
Sure.
Second, would the aim be to use F-VASI75 as an approvable endpoint for povorcitinib, or is there a different approvable endpoint you're considering? Third question, switching to Opzelura. I'm curious what the message to physicians is going to be on the back of this long-term vitiligo data. Is the marketing message gonna be, you know, keep patients on long-term because if you don't, you know, a reasonable proportion will lose their response? Or is it to say patients can try to come off drug after they've gotten a good response, and if they lose it, don't worry, the data shows they can get it back. Thank you.
Maybe I'll take the first two.
Yeah.
Then, ask Dr. Pandya to address the third question. In terms of the povorcitinib phase II study, the variability, and so, we're gonna share data obviously out to year one and actually longer. Dr. Pandya mentioned that repigmentation is a slower process. I think what we see later is that the repigmentation accelerates over time. I think you saw that with the week 36 versus the week 24. Part of the challenge at week 24 was because of the slower repigmentation, especially in patients with more extensive disease. As well as the smaller cohort size, it probably led to some of the variability as well as what Dr. Pandya mentioned about the F-VASI assessment.
The data is very good, you know, week 36 will clearly look better and the variability reduced as you go farther out, as these patients are repigmenting more. As they repigment more, to Dr. Pandya's point, the F-VASI assessment, there's less intraobserver, interobserver variability. In terms of. Actually, I just forget the second question. I think it was.
What. Yeah. What would you expect the approval endpoint to be for pilsicatinib? Should we think of it as being F-VASI 75, like for Opzelura, or is there a different approval endpoint you'd be pursuing?
We typically don't discuss the regulatory strategy. You know, whenever you have a new drug approval and a new indication, you should look at the regulatory or the endpoints that were used for the approval. And that'll give you an idea for what's gonna be required for subsequent products. You know, it's likely gonna be the facial F-VASI75 as the primary efficacy variable.
In terms of the way that I would think about the long-term data, I think that the long-term data is exciting because it shows that people continue to improve, and I would say continue to use it to the patients and also the dermatologists until you plateau, until the patient plateaus, because we haven't quite seen a plateau even now after two years. There's good reason for even those patients who have partial improvement to just to keep going until the plateau happens. In terms of stopping it and then having to restart, I feel like that's also something that's good news, although I would not really recommend stopping it until you do plateau. Then it's exciting to know that you can repigment when you do stop it and the patient does have a relapse.
I also think that I would tell dermatologists that in the long term, you may not need to use Opzelura every single day. In the long term, we need to do further studies to find out what a good maintenance would be. We all feel like biologics are something that you use long term. We all know that if you stop the biologic, the psoriasis is going to come back. Dermatologists are used to that, of having patients on it for years and years and years, because we know that the pathogenesis of the disease is just that way.
Yeah. One more thing, just to add my two cents. I think the continued safety profile is really encouraging now out, you know, a further year with no other serious events and, you know, the same degree or less of acne or pruritus at the application sites. That's very reassuring for us.
Great. Thank you.
The next question comes from Salveen Richter with Goldman Sachs. Please proceed.
This is [Madon] for Salveen. I had a few quick ones if that's all right. I was wondering first, could you guys just specify. I know 29% relapsed after stopping Opzelura, in the patients that achieved a complete response. What percent relapsed while continuing treatment? What percent of those went below 75? I have a couple more.
Sure. What Dr. Harris presented, there were a few patients in the arm that was re-randomized to ruxolitinib cream. I think it was around 21%, 22% of those patients dropped below the facial F-VASI 90. I think 14 maybe dropped below facial F-VASI75. We think that, you know, most of that, to Dr. Pandya's point, was due to patient compliance with the continued treatment of medicine.
Got it. Got it. Thank you. In terms of, it sounds like, and I know you haven't confirmed this 'cause it's early, but it could be F-VASI75 for an approval endpoint. I mean, right now, I mean, just I guess the question for Incyte is, do you guys plan to advance this to a later stage study? Are you still considering it or do you need to see the longer term data before you make a decision to advance? In terms of the comparability of the impact on facial scores versus Opzelura, it seems like, you know, it was a little. At week 24, it was maybe a little bit less, 15% placebo-adjusted versus around 23% for Opzelura. At week 36, it becomes, it looks very comparable.
you know, I guess if you can get that's probably enough to get approved if F-VASI75 is the endpoint. I'm also wondering, you know, are you gonna get patients just wanting to take the pill instead of putting on the cream, just given how, you know, more convenient and better compliance-wise that is? I mean, I know safety is a consideration, but just interested to hear your thoughts there. Thank you.
Sure. Let me address your second question, and Dr. Steven Stein will address your first question. In terms of the comparability, obviously you need to always be careful comparing between studies because it is a different patient population as Dr. Pandya pointed out. This was a much more severe patient population. If you take a look at the Opzelura data, we got about 30% of the patients were able to achieve facial VASI 75 at week 24. That bumps up to 52% or about 50% at week 52. It is a little bit less than that. Again, you have to be very careful 'cause you have two distinct different patient populations. You had a pretty.
You know, you had a pretty extensive facial involvement in the povorcitinib study. But that being said, we're very excited about the data with povorcitinib. I think as we come out with the week 52 data, hopefully everyone will see that with continued dosing, give people more time to repigment, that povorcitinib will be a very good treatment option for vitiligo patients. Maybe I'll ask Dr. Stein.
I'll just lead off with a few editorial comments. I mean, I think, you know, Dr. Pandya said it well. You have ignited the field in terms of vitiligo research, which is really great. You know, lots of other mechanisms being pursued, many other companies looking at it. In some way, in terms of the endpoint, it comes back to our own history in myelofibrosis. You know, more than 12 years ago, the spleen volume response rate 35% or greater endpoint was really invented by Incyte, used in the initial COMFORT-I study and then became the de facto regulatory endpoint therein. I think, you know, as Jim said it well, you have to look at precedents now. It's very likely that the FDA will look at facial VASI 75 as their surrogate for clinical benefit going forward. That's what we expect.
We haven't yet made the internal decision to go, you know, full steam ahead on a regulatory program. You know, this data is, in our minds, you know, really, really encouraging, dash outstanding. I think, again, Dr. Pandya said it well. You know, one way to view this is a compliance play versus the cream. I think you made an outstanding point there where people can take an oral pill a day and don't have to apply cream twice daily. Those will all factor into our de-decision, plus regulatory discussions coming up soon. The other flip side, you know, maybe to make somewhat of a sort of fair, balanced comment is the view on JAKs in general at the FDA and class labeling.
We eyes wide open on the likelihood of, you know, future JAK inhibitors in inflammatory conditions getting black box warnings, and that'll play into the decision-making. Just to end positively, encouraged by the data. You know, love the view that this could be used for more severe patients. Great compliance. Pending regulatory discussion, we'll make the decision on whether or not to go full steam ahead. Thanks.
Great. Thank you, guys.
The next question comes from Mara Goldstein with Mizuho Securities. Please proceed.
Hi, this is Jerry Gongon from Mara Goldstein. Thanks for taking our questions, congrats on the data. Two on Opzelura for me and then one on povorcitinib. Starting with Opzelura, I kinda wanna, you know, follow up on the question on the, you know, kind of relapse patient rate in the withdrawal arm. I think about 29% relapsed. Then I think in the presentation, around 40% maintained a response and some 20% discontinued treatments. Can you kinda share what happened to the remaining 10% of patients, or am I thinking of this the right way?
I'm sorry. There was some background noise. Could you repeat your question?
Oh, sorry. Yeah. In the withdrawal arm, for Opzelura, about 29% of patients, you know, relapsed on treatment. From the presentation itself, about 40% maintained a response and about 20% discontinued treatment. Kinda what happened to the remaining 10% of patients, kinda not accounted for in those numbers?
Yeah. I think, I'm sorry.
We're in New Orleans, and there's jazz bands playing on the street outside.
There's a trumpet playing out right outside of the room. I think I heard that what happens to those patients in the long-term follow-up when they lost the facial, either facial VASI 90 or facial VASI 75? I don't know.
we can talk about it as well, but, my question is more about like, you know, the patients that weren't accounted for, in the relapsed and response kinda maintained, group in withdrawal arm.
Jim, if I understand-
Yeah.
I think if you focus on the 29%.
Right.
that relapsed, if you can just talk about that group a little further. That's the best I understood the.
In the vehicle arm or in the active arm? The vehicle arm, right?
The vehicle arm.
The vehicle arm. Yeah.
The vehicle arm, right. Is it safe to think about like the other, you know, the other 70% of patients responding to treatments? How should we think about that?
You said something about other studies. Are you asking us to compare-?
No. Sorry.
the two?
No, no. Sorry. 29% relapsed, right? What kinda happened to the other 71% of patients? Did most of those maintain a response? Yeah.
What happened to what?
The other remaining 71% of patients.
What happened to the other systems? Maybe a little slowly.
Yeah.
What happened to the other systems? Is that what you asked?
The other remaining 71% of patients.
Oh.
Oh, the other remaining 71%.
Yeah.
of patients in that particular-
Yeah. I'm sorry.
Okay. Thank you.
Okay.
Sorry about that. We have a Mardi Gras band outside our window.
No. No. That was the vehicle arm. When patients relapse, obviously they restarted. Many of them didn't relapse and didn't need additional treatment, especially the ones... As long as they maintain the facial VASI 75, and it was a very large number of them, right? The ones that did relapse, and then, you know, the other patients, some of the patients, we had some dropouts. In that arm, you know, we started with 110 and ended up with 90. All of the patients were accounted for, but most of them actually did not drop below facial VASI 75. They did not basically go back on active treatment.
This is what I in practice when I have patients on, you know, I haven't used Opzelura for over a year, when I see that success and then the patient stops treatment, there are many who maintain that improvement for a year. Slowly but surely, the patients who, you know, had significant vitiligo to begin with, it creeps back at year two, at year three, at year four. I think that that 71% of patients will that number will slowly go down over time when you go past a year.
Got it. Keeping with Opzelura, you know, we saw some benefit, from patients that relapsed, then restart treatment in the vehicle arm. How are you thinking about, you know, the length of drug holiday and how it might affect the time it takes to regain a response?
Maybe I can ask Dr. Pandya to talk about the length of drug holiday based on his experience, extensive experience with vitiligo patients.
Yeah. I think you can take a drug holiday usually for up to three months without really relapse. After about three months, then that's when I start seeing relapses, no matter whether you're taking a holiday from phototherapy or topicals. I think that would be kind of a reasonable period of time where you can expect not to have a relapses for about three months.
If a patient in your practice comes back in month six and they've started to depigment, that's when you would start the patient back on treatment.
Back on treatment.
Yeah.
You know, some of them will say, "I need to take three months off this summer, and I can't do phototherapy, I can't do topicals or whatever." I'll say, "Okay, you probably will be okay. I would recommend you get a little bit of sunlight, you know, and, you know, get a little bit of sunlight, but you'll probably be okay. If you go beyond three months, then you're risking relapse.
The data that we showed around, you know, regaining the pigmentation after relapsing, that would be reassure you that you would restart that patient on Opzelura.
Right.
Perhaps we'll take one more question and then end the evening. If there is one more question.
The last question comes from Evan Seigerman with BMO. Please proceed.
Hi, guys. This is Keith Bachman on for Evan. Thanks for taking our questions, and congratulations on the data. I have two quick ones. The first is could you, for the upcoming phase II data for RUXO + phototherapy combo, just wanted to know what your expectations are in terms of the step up in efficacy, and any feedback on the FDA on the outcomes for the combo trial. Secondarily, more of a practice question. One of the doctors today mentioned a four-month waiting list for appointments. I imagine in dermatology this is the case broadly. Just wondering what you can expect in terms of evolving clinical practice given the safety of Opzelura. Would you expect this to extend to primary care, at least in terms of maintenance therapy? Thanks.
Okay. Maybe I'll address the first part and Dr. Pandya address the second part. The phase II study in combination with UVB light therapy. Dr. Pandya was actually intimately involved with that study and helped us design it. After 12 weeks of Opzelura therapy, if a patient doesn't have a response, and I believe it's facial VASI-
Twenty-five
...25%.
Oh, T- VASI.
T- VASI 25. Excuse me. T- VASI. That patient is continues with Opzelura, but UVB, you know, light therapy is added. The patients who actually are able to achieve a total VASI 25 at week 12 continue with monotherapy of Opzelura. That's how that study is designed. It's ongoing. And we hope to have the data as soon as possible. Again, that's basically to help guide physicians, right? For a fast responder, Opzelura is good just by itself. There's no need to add anything else. For the patients whose melanocytes are senescent and not, you know, waking up, that's where the light therapy can certainly help boost that response in those patients.
I fully expect the T- VASI, I fully expect the vast majority of those patients will have a T- VASI75 at month 12, with the phototherapy. The second question was, once again?
Around the wait times, four-month wait times.
Right
...in practices.
65% of skin care in America is taken care of by primary care doctors. Primary care doctors do treat acne, psoriasis, eczema. I think that vitiligo is something that they're not so comfortable with. This is an opportunity with Opzelura and with Incyte educating physicians and patients coming in to see doctors. They can't see the dermatologist in for 5 months, but they can see their primary care doctor perhaps next week. It's actually a very easy medication to prescribe.
Okay. On that, we'll end. Thank you, Dr. Pandya. Thank you very much. Thanks to everyone in the audience and online. Have a good evening. Cheers.