Hello, welcome to the Incyte Opzelura approval conference call and webcast. At this time, all participants are in listen only mode. A question and answer session will follow the formal presentation. In the interest of time, we ask that you please ask one question, then return to the queue. As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to Christine Chiou. Please go ahead.
Thank you, Kevin. Good morning and welcome to Incyte's conference call and webcast to discuss the FDA approval of Opzelura, which was announced yesterday. I have the pleasure of introducing Dr. Larry Eichenfield from the University of California, San Diego. He is Professor of Dermatology and Pediatrics, Vice Chair of the Department of Dermatology, and Chief of Pediatric and Adolescent Dermatology at UC San Diego School of Medicine and Rady Children's Hospital-San Diego. He has also served as an investigator on some of our studies. Speaking on the call today from Incyte are Hervé, Jim Lee, our Head of Development in Inflammation and Autoimmunity, and Todd Edwards, our Dermatology Business Unit Head. Larry and Christiana will also participate in the Q&A session.
Before we begin, I'd like to remind you that some of the statements made during the call today are forward-looking statements and are subject to a number of risks and uncertainties that may cause our actual results to differ materially, including those described in our 10-Q for the quarter ended June 30, 2021, and from time to time in our other SEC documents. We'll now begin the call with Hervé.
Thank you, Christiana, good morning, everyone. Thank you for joining today's call to discuss the approval of Opzelura, the first FDA-approved topical JAK inhibitor for the treatment of mild to moderate atopic dermatitis inadequately controlled by topical therapies. This approval is an important milestone for patients and also for Incyte. Today marks the expansion of our commercial portfolio into inflammation and autoimmune diseases and adds an important potential contributor to diversification and growth. Opzelura is a first-in-class novel medicine addressing a clear unmet medical need for patients suffering from atopic dermatitis who are not controlled by topical therapies. This unique positioning between current topical and systemic treatment has the potential to help the many patients who have inadequately controlled AD who could benefit from Opzelura's profound impact on inflammation and itch.
Recently presented data, including follow-ups for one year, showed that patients have the potential to achieve long-term disease control with the intermittent use of Opzelura, providing physicians with an important new therapeutic option. The unique topical cream formulation allows for targeting inflammation directly at the affected site, providing significant and rapid itch relief while also minimizing systemic exposure. A few weeks ago, the FDA provided an update related to oral JAK inhibitors treating inflammatory condition, which resulted from a review of an oral JAK inhibitor in treating rheumatoid arthritis. A class warning is also noted in our label. As a topical formulation with limited systemic exposure, Opzelura is a highly differentiated treatment compared to oral JAK inhibitors. With the strong safety and efficacy data included in our label, Opzelura is expected to deliver a significant benefit for patients with uncontrolled atopic dermatitis.
We are excited to bring this much-needed innovative therapy to patients suffering from eczema. With that, I would like to turn the call over to Jim Lee, our Head of Development for Inflammation and Autoimmunity. Jim?
Thank you, Hervé. Good morning, everyone. I wanted to highlight some of the sections of the prescribing information for Opzelura. This slide describes the indication in dosing and administration for Opzelura. Opzelura is indicated for the topical, short-term, and non-continuous treatment of mild to moderate atopic dermatitis in non-immunocompromised patients 12 years of age and older who are not adequately controlled with other topical therapies. In terms of dosing, the recommended dosage is Opzelura cream applied twice daily to affected areas up to 20% body surface area, with total cream use not to exceed more than 60 grams per week. Slide seven shows the eight-week efficacy data from both Phase III studies that is included in the Opzelura label.
After treatment with Opzelura for eight weeks, over 50% of the patients achieved clear or almost clear skin, as measured by an investigator global assessment or IGA score of zero or one, with at least a two-point improvement from baseline. In addition, a significantly higher number of patients treated with Opzelura versus vehicle achieved a four-point or higher improvement in itch reduction. Opzelura is the first and only approved topical product for atopic dermatitis to demonstrate a statistically significant improvement in the ITCH NRS4 patient-reported outcome. Next, let's discuss the safety. The safety data in our label, shown here, highlights the adverse reactions in greater than 1% of subjects in the randomized portion of the study through week eight from our TRuE-AD pivotal program.
The percentage of patients with treatment-emergent adverse events is comparable between the Opzelura arm and the vehicle arm, with 27% and 33% of patients respectively experiencing a treatment. On the next slide, we want to address the box warning, which reflects serious conditions observed in the safety review of oral JAK inhibitors. This review was initiated with the FDA review of an oral JAK inhibitor treating rheumatoid arthritis. We believe the safety data, as well as the limited systemic exposure observed with Opzelura, did not warrant a box warning. Despite the class labeling, we believe Opzelura, with its robust efficacy and safety profile, will deliver a significant benefit for patients with uncontrolled atopic dermatitis. In terms of addressing the components of the box warning, this slide shows the incidence of events during the vehicle control period of the Phase III studies.
There were no non-melanoma skin cancer malignancies in the Opzelura arm during the vehicle control portion of the study. There was an elderly patient in the Opzelura arm who developed a skin cancer. This lesion was not in the treatment area. It was not felt to be related to treatment, and the patient was able to continue in the study after treatment. Similarly, with MACE, there was one case in the Opzelura arm in the randomized portion of the trial, which again, was not considered related to treatment due to the patient's history of multiple cardiovascular risk factors. Given the data and what is in our label, we expect that physicians will be able to see the differentiated safety profile of Opzelura and distinguish it from the rest of the class. In the next section, I want to review some of the data that is not included in our label.
As a reminder, in the TRuE-AD studies, there was an eight-week randomized portion, at which point patients on vehicle were allowed to be treated with Opzelura. Patients were then treated on an as-needed basis for an additional 44 weeks, similar to how they will likely be treated in a real-world setting. On this slide, you can see the effective long-term disease control in patients treated with Opzelura. Nearly 80% of patients achieved and maintained clear or almost clear skin, a goal of treatment showing the ability of Opzelura to achieve a high level of disease control and stabilize patients' disease with intermittent therapy. With that, I would like to turn the call over to Dr. Lawrence Eichenfield.
Good morning, everyone. I work out in San Diego, where I'm a professor of dermatology and pediatrics and work at Rady Children's Hospital as well. I have a long-standing interest in eczema and atopic dermatitis and have been asked to sort of review the treatment landscape in atopic dermatitis and really the clinical need, ending with why I think this drug will be so important in our clinical care. Start it off with what I call the short story of atopic dermatitis. This is a highly prevalent condition. We know that it's present in and develops in 10%-20% of children with a high prevalence in adolescents, and pretty good data now in the U.S. of about 7% of adults having it.
We'll discuss sort of the manifestations of eczema, and because of those manifestations, it really brings a significant burden to affected individuals and also comorbidities. Just go back one slide. The other issues associated with atopic dermatitis, it has a variable course of severity. There are some patients who are very mild, and there are patients who are very severe, and there's a lot of patients in between. We'll also, as we go through some images of eczema, discuss the sort of differences between quantity of eczema someone has and severity. Atopic dermatitis also has different triggers in different patients, has a mixed immune pathogenesis in many patients.
Despite the availability of a variety of topical therapies, there's basically a high unmet need, both in terms of a desire for faster minimization, amelioration of itch, and for long-term disease control, which is really the model that we're going for with our care of eczema patients. Next slide starts off with sort of the core manifestations of atopic dermatitis. First of all, you get the eczema rashes, oozing, crusting, scaling, redness, heat, and pain associated with it. Itch is very much wrapped with atopic dermatitis. Itch can propel further rashes through scratching, but itch is also a symptom complex that impacts the life of the individual. Dry skin and xerosis is clearly a part of atopic dermatitis in terms of both the pathogenesis and drives some of the manifestations of the disease.
There are some people who are born with inherent barrier dysfunction, meaning their skin's a little bit more open. It's more open, it dries out because of evaporation. That also makes the skin more vulnerable to things that get on the skin that stimulate the inflammation. The inflammation is tantamount to the clinical aspects of the disease and something that we need to have effective agents to manage. There's also secondary infections. Some of the images here show some of the staph pustules or impetigo-type secondary infections that we have. There's a chronicity to atopic dermatitis with, in many patients, it being recurrent, also a subset where it's very persistent and needs a continuous or discontinuous control model to minimize the impact on the disease. Of course, there are many patients who have intermittent flares that needs to be managed.
Itch is clearly an important part of the manifestation of atopic dermatitis. We go to the next slide, you can see just some of the data points that have been collected. In some data sets, patients report that 88% of days have itch associated, 69% of more moderate patients reporting that itch can be at least 12 hours a day. This itch impacts on sleep disruption as well, very commonly. Going to flip over to a few images of eczema. In clinical practice, we see eczema of tremendous variation on a daily basis. You can see in the upper left, you have a pretty typical pattern of a localized arm lesion. You see redness, you see some crusting. On the upper right, you see localized areas that are thickened.
The middle image underneath just shows what we call acute eczema, where there can be oozing and crusting from eczema. Eczema in the Greek actually means to boil over, where the inflammation causes oozing up to the surface. The next slide shows a moderate patient who has localized atopic dermatitis, predominantly in a classic eczema body fold area. I do think it's important to know that in clinical practice, unlike in clinical studies, the way we look at severity is a mixture of extent, but also the qualities of the eczema. It's not just a body surface area eruption. We have plenty of patients with mild to moderate disease who have tremendously bothersome atopic dermatitis. The next slide is just to point out if there's facial dermatitis, you can figure out how that impacts the individual, and how it can impact on social activities, on the workplace.
You can also see a localized eczematous eruption on the legs, again, showing some thickening. You can understand that there is inflammation here as well as dryness, and you can overlay the concept of itch on top of it. The next one’s one of my adolescent patients, just showing that you can have diffuse involvement. You can see the redness that comes from inflammation as well. The next slide just represents to not forget that there is a significant amount of discoloration that comes along with eczema as well, with both brownish or whitish discoloration as part of the burden that patients face with the disease as they go out into real life with their eczema, especially if it’s not under control.
The pathogenesis of atopic dermatitis is pretty complicated, but I just wanted to emphasize that there's really sort of a unified perspective that we have inherently, in some individuals, dry skin, or even if they're not inherent, if you have active eczema, it means that that skin barrier isn't normal, so it doesn't protect the skin normally. It goes along with this tendency to get inflamed and to have itching. These impact on cytokines and inflammation and the immune activation, and that that immune activation impacts on the skin. Looking at atopic dermatitis, we know that there's going to be this immune activation that's going on and this set of cytokines, and it really creates a challenge for us to be able to control the immune system and immune infiltration in the skin.
We want to target that inflammation either directly at the site, as we do with topicals, or systemically. The next question I'm going to ask is, atopic dermatitis, eczema, why does it matter? This really gets at the burden of the disease and something that we play through with patients in clinical practice. I've set up a sort of circle or cycle of atopic dermatitis that if you start at 9:00 P.M., we start with the eczema and the rashes, which I've shown you. Right above that, as you get to around 10:00, 11:00, is the symptom complex, where you have frequent and intense itch. Sleep disturbance, which of course, is influenced by itch, and pretty typically, patients can report problems getting to sleep and problems staying to sleep. This obviously can have an impact on all the aspects of someone's life.
At around 1:00, I've listed the atopic comorbidities because atopic dermatitis is associated with asthma, nasal rhinitis, food allergies, allergic conjunctivitis. We have a set of non-atopic, non-allergic comorbidities, which includes bacterial infections and other infections, mental health disorders, which I'll go to in a little bit more detail, but with anxiety and depression being seen very commonly in our eczema patients. Other immune-mediated diseases and potential cardiovascular diseases, though conflicting studies on that. Impaired quality of life then is really a consequence of a lot of the circle that I presented. It can impact on daily activity, social functioning, life course decisions, and then on school and work productivity.
Whether it's a teen in high school who's not sleeping because of his eczema or someone at work either unable to go to work or not sort of being present and as successful at their work because of these secondary effects of the eczema. The next slide highlights what I call make sure that we stress that the impact of atopic dermatitis can be on the individual in many ways, and also the family. In significant eczema, there's emotional distress, embarrassment, and social isolation. That could happen even with mild eczema when it's in areas that people can see, like facial dermatitis or on the arms if someone's not wearing longer sleeves. Depression and anxiety, there's very strong data about higher rates of depression and anxiety with atopic dermatitis. You can imagine issues with teasing and bullying in our teens, especially.
A lot of patients, if they don't have long-term disease control, end up limiting their activities. For instance, if heat and sweating impacts their eczema and flares their eczema, they can avoid their sports or if they just don't want to show off their lesions in fear of a trigger making their eczema worse. Sleep disturbance clearly is very much wrapped in pruritus to itch. One of the reasons why we're looking for products that can do better at controlling itch. Sleep disturbance clearly impacting on school and work. Then the family data is pretty impressive. Maternal sleep disturbance is very common with atopic dermatitis, even in mothers of teens, of adolescents with atopic dermatitis. There can be an exhaustion effect beyond the individual.
Let's move over to what the landscape is for treatment in atopic dermatitis. I'm not going to do an hour and 10-minute talk. I'm going to do this in about three minutes. There's a basic management schema for atopic dermatitis, which is good skin care, gentle bathing, frequent moisturizer use. If there are known irritants or allergens, they're avoided because eczema skin can be sort of twitchy. There are some adjuvants, such as antihistamines and bleach baths, that are used in some individuals. When there's inflammatory eczema that's not controlled with moisturizers, which is most of atopic dermatitis eczema, we use anti-inflammatory agents. Topical corticosteroids are our first line of therapy.
The range in strength of topical corticosteroids, as assigned over-the-counter hydrocortisone 0.1, we have topicals that are 2,200 times stronger, and that feeds into concerns about their use in terms of secondary effects with skin thinning or absorption of corticosteroids and the effects. We have now three non-steroids that we've had, both topical calcineurin inhibitors, which we saw at the beginning of the century with pimecrolimus and tacrolimus, and then PDE4 topical crisaborole. Beyond the topicals, in more and more severe patients, we do have our first biologic that's been approved, dupilumab. Oral corticosteroid is the only drug that traditionally was approved until dupilumab, although they're not advised to be used because of side effects. Traditional immunosuppressives that were hardly ever used in the U.S. because of their potential toxicity, and then phototherapy.
In our basic management, there's been a tremendous clinical need in that we have issues with our topical steroids, and our non-steroids have limitations. They have limitations because of stinging and burning as side effects, and they don't have especially strong efficacy as compared to the Opzelura data, although we haven't done head-to-head or with a topical corticosteroid. We just know that there's a limited efficacy in our non-steroids to date. Which brings us to sort of real-life situation of where are we at with atopic dermatitis. As a practitioner who's going to see lots of eczema patients later this morning, I know that there's a lot of under-treatment of atopic dermatitis. There's concerns, a lot of phobias with topical corticosteroids and topical calcineurin inhibitors. Topical corticosteroids create concerns about skin thinning.
The PDE4s definitely have tolerance issues with stinging and burning being a limiter in many patients. We have limited efficacy in terms of non-steroids. We have the situation where long-term disease control is the goal, but we are very commonly not meeting that goal. Even though we've had our breakthroughs in systemic therapy for atopic dermatitis and other medicines being developed, most patients are going to be treated with topical medications, with systemics being restricted for more severe patients. Having extension of medications in the topical realm that can bring the desired long-term disease control is very important to us. I want to translate this. With the next slide, how will Opzelura fit into eczema care? I really think it'll be an incredibly important drug for us, and that it'll have broad application. Why?
Well, a lot of it comes down to looking at the efficacy and safety data. You heard a brief summary of the percentage of patients who made it clear to almost clear, and the percentage of patients who had an incredible drop in their itch score from their baseline. That's the pairing that we're looking for, right? Patients who are essentially clear and have a marked decreased itch. The robust efficacy, I think, is quite important. I believe that we don't have that level of efficacy from our other non-steroids that we've had previously. It's one of the things that makes it so exciting. I think especially the impact on itch, since itch so much drives the clinical process of the disease. Opzelura being a topical JAK inhibitor is not associated with skin thinning.
Wouldn't expect to do that, unlike topical steroids that are known to have that problem. That limits topical corticosteroids on delicate skin areas like the face, where Opzelura, we have a chance to use it on all impacted areas. The data shows a consistent effect across different populations, which I think is important. It was studied 12+ and also in a population that was diverse in many ways. I think we have this unmet need. The most severe patients may go on systemic medicines, but there are many patients with mild to moderate disease, and this will be where I believe Opzelura will fit in because of its efficacy and relative safety.
I won't be part of the question and answer period, but I thought I would just ask a question that I think would be asked and then answer it, which is, what do I think about the boxed warning and how that might influence use among the primary market, which will be dermatologists, and then the secondary, other providers who might use it as well. To start off with the dermatology community, dermatologists have dealt with boxed warnings before. isotretinoin or Accutane is a drug that has an impressive boxed warning and significant side effects. It's the breakthrough medicine that has been used now for decades to fix acne. People recognize that doing a risk-benefit in their experience in real use brings their ability to use that medicine. I think dermatologists are also quite skilled at trying to get a sense of the warning.
The boxed warning as we read it is about oral JAK inhibitors and specifies oral JAK inhibitors. I think they'll read through the rest of the prescribing information and get a sense of the warning and remember the strong data about Opzelura, both efficacy and the safety data which you saw briefly presented by Jim. Even what's in the box warning is different than seen in the Opzelura data. I think dermatologists are good at parsing that out and most importantly, being able to relate the information to their patients because they know that we have an unmet need with atopic dermatitis, and we're still quite excited about how that will fill in to bring more patients to disease control over time to minimize the impact of eczema on those individuals. Now I'm going to turn it over to Todd.
Thank you, Dr. Eichenfield. I'm excited to be here today to share with you a high-level view of the commercial plan to ensure the successful launch of Opzelura, which has the potential to significantly help millions of patients in the U.S. suffering from inadequately controlled atopic dermatitis. Based on the compelling data from our phase III program and the feedback we have received from physicians and patients alike, we are starting from a position of strength with Opzelura's highly differentiated safety and efficacy profile. Before I provide details on our strategy to drive product awareness and adoption, I want to remind you of the significant unmet need that exists in atopic dermatitis today. In the U.S., we estimate there are approximately 21 million patients that are 12 years and older living with atopic dermatitis, of which 5.5 million are drug-treated.
The vast majority are treated with topical therapies, with approximately 10% of patients on systemic treatment. A small percentage of these patients are controlled with their current therapy. For the large majority, disease flares and itch continue to persist. In a recent survey of 600 patients, only 22% of patients reported that their AD is well controlled with current therapy. More than 40% of these patients said they experience flares at least once a week, and nearly 50% of patients said they experienced AD-related cracks in their skin in the last month, again highlighting the impact this disease can have on patients' lives. For patients who have an inadequate response to topical steroids or topical calcineurin inhibitors and may not require or be eligible for systemic therapy, there has been a significant dearth of novel effective therapies.
Prior to the FDA safety review of the oral JAK inhibitors, we showed dermatologists a blinded profile of Opzelura, and 85% indicated they would likely prescribe this treatment to their patients. We tested the class box label hypothesis with dermatologists more recently, which resulted in dermatologists reducing their prescribing by approximately 15%. The importance of Opzelura as a new option for the treatment of atopic dermatitis is very clear when you consider the differentiated value of Opzelura and understand the needs and wants of patients living with uncontrolled atopic dermatitis. When it comes to treatment, itch reduction is cited as the number one treatment driver by dermatologists. Opzelura is the first and only approved topical therapy to demonstrate a statistically significant and clinically relevant improvement in four-point or better reduction in itch. Second, both parties, patients, and dermatologists prefer topical formulations, and Opzelura is a non-steroidal cream formulation.
Lastly, patients want to have clear skin. In the TRuE-AD trials, more than half of patients achieved IGA skin clearance of zero or one by week eight. Let's now move on to discuss our dermatology commercial team. We have recruited top talent from leading dermatology companies. These are high-performing experts in their field with significant experience within dermatology. In fact, 80% of our field-facing team were ranked in the 90th percentile for performance at their prior company. The average length of our reps' dermatology sales experience is 10 years, with 100% of them having pre-existing relationships with dermatologists. We also recruited dedicated experts in payer account management with deep experience in dermatology or similar specialties to swiftly garner preferred access for Opzelura. We are focusing our efforts on targeting dermatologists, NPs, PAs, and high-priority allergists who write the majority of atopic dermatitis prescriptions.
78% of all market prescriptions for AD are written by the top 20% of dermatologists, NPs, PAs, and allergists. We believe reaching these physicians will have the greatest impact to ensure Opzelura reaches the most relevant patients who need an alternative treatment option. We will be launching a comprehensive and targeted multi-channel marketing campaign that will ensure we have broad and consistent reach that will generate high awareness of the compelling impact on itch and inflammation that can be achieved with Opzelura, and also highlights the benefits of a topical formulation that is well-tolerated and aligns with the dermatologist's preferred treatment choice. We expect Opzelura will be available to patients by the end of the week of October 4th. We have had multiple meetings with payers to discuss the unique attributes and value of Opzelura. I'm very encouraged by their engagement and keen interest in the asset.
We believe Opzelura's payer value proposition is clear, and we will work with payers to finalize access agreements. At launch, we expect over 100 million lives to have variable access to Opzelura, and a smaller number would have a new-to-market block. In either event, we have support programs in place to ensure patients have access to Opzelura. As contracts are finalized, we expect the removal of new-to-market blocks and anticipate having attained streamlined and sustainable access for patients by early 2022. Let's briefly touch on IncyteCARES. This program supports eligible commercially insured, underinsured, and uninsured patients in the U.S. Upon launch, our IncyteCARES program will enable all eligible AD patients access to Opzelura. For those patients who are commercially covered, our co-pay savings program offers an out-of-pocket cost as little as $10.
For patients with prior authorizations or appeals, we have partnered with CoverMyMeds to assist dermatology offices and pharmacies in gaining access to Opzelura. We have a process in place to make certain commercially insured patients with no coverage have access to Opzelura. Finally, for eligible patients with no insurance or for those who may be underinsured, our patient assistance program may provide free product assistance. Turning to slide 39. In summary, Opzelura has the potential to address a significant area of unmet need for patients living with atopic dermatitis. We expect that Opzelura will reach a peak sales of at least $1.5 billion. This estimate assumes patients will use three to four tubes per year and is based on a WAC of $1,950 per tube.
Our estimate also includes a typical dermatology gross to net of 25%-50%, which takes into account several variables such as patient assistance programs, negotiated rebates, and co-pay programs. We'd like to note that we anticipate higher utilization of patient support programs while we are waiting for Opzelura to achieve preferred access, and therefore, a higher gross to net during the fourth quarter of this year. Now, I will pass the call back to Hervé.
Thank you, Todd. As you heard, we are well positioned for a very successful launch of Opzelura. This approval is a significant milestone for Incyte dermatology, and we have several additional near-term efforts to build on the opportunity with ruxolitinib cream. Earlier this year, we reported successful phase III results of ruxolitinib cream in vitiligo, and we are excited to be able to share with you the 24-week data at EADV later this year. Based on these results, we are planning to submit an SNDA for ruxolitinib cream in vitiligo by the end of this year, positioning us for potential launch next year. We also initiated a pediatric phase III program in patients aged 2 to 11 with atopic dermatitis, and we will continue to explore other indications that may expand the use of ruxolitinib cream to additional patient populations in need.
Now operator, please open up for Q&A with the Incyte team. Thank you.
Thank you. We'll now be conducting a question and answer session. As a reminder, we ask you please ask one question, then return to the queue. If you'd like to be placed in the question queue, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. Once again, that's star one to be placed in the question queue, and we ask you please ask one question, then return to the queue. Our first question today is coming from Marc Frahm from Cowen. Your line is now live.
Hey. Thanks for taking my questions and congrats on the approval last night. Jim, you reviewed the data supporting or not supporting the warning statements in the randomized portion of the eight-week trials. If you read deeper into the label, there's maybe some more data in some of the longer-term follow-up or maybe the vitiligo longer-term use randomized trial that support that some of those warning statements may actually have happened within Opzelura experience. Can you review what's happened in those longer-term follow-ups? Related to that, maybe this is for you or for Todd, just how do you expect these warnings in the indication statement of non-continuous use to be implemented in clinical practice?
Sure. Thanks, Marc, for the question. Maybe I can refer to our label. Hopefully, you had a chance to review it and specifically section five, which is the warnings and precautions section. If you want to or did go through each of the warnings and precautions, 5.1, serious infections. Again, the only thing that we've seen in the Opzelura trial that's highlighted there is viral reactivation. We did see a few cases of zoster in the study, but remember that atopic dermatitis patients have a twofold increased risk of developing zoster. It's not clear that those cases were related to treatment. 5.2 mortality, we didn't see anything. Malignancies, lymphoproliferative disorders, you can see that the lymphoma specifically called out oral Janus kinase inhibitors. We did mention that we did see non-melanoma skin cancers in our studies.
Please keep in mind that in many dermatology studies, as a patient shows up who hasn't seen a dermatologist, that a lot of times they tend to show lesions to the doctor, to the investigator. In the TRuE-AD program, which included the vehicle control period as well as the long-term extension, we had a total of four patients who reported basal cell carcinoma and squamous cell carcinoma. SIx events, one patient had three lesions. Actually all four patients, the lesions occurred in non-treatment areas. Again, it's hard to imagine that any of those lesions were related to treatment. In terms of 5.4, the MACE events, again, you can see that there's no mention of Opzelura specifically or no mention of events in the trials. In terms of the thrombosis, we did report or we did see two cases of PE1.
I think it was a week 41 patient. It was a 61-year-old with a prior history of DVT and PE, as well as a family history of a DVT and PE. In the lower strength, we had a case of a young female on a birth control pill that's actually known for having a higher risk of DVT and PEs. Those are the two events, but you can see that even FDA wasn't clear whether those events were related to treatment. In terms of the last warnings precautions that's relevant, lipid elevations, we didn't see any changes there, but thrombocytopenia, anemia, neutropenia. We did have a handful of events during both the vehicle control period and the long-term extension, and all of them were not clinically relevant, meaning most of those patients, I think most of the patients actually started at the low end.
If their hemoglobin was 10.6 at baseline and went down to 10.2, we didn't really feel those were clinically relevant. None of those patients were symptomatic. They were not associated with any adverse event. Honestly, when we looked at the PK of those patients, there was no elevation, so they weren't associated with systemic exposure. I think that if a patient has a history of anemia, if a patient has a history of thrombocytopenia, physicians should consider checking a baseline lab, and that's why the language of clinically indicated is in there. Those are the summary of the warnings and precautions. Hopefully that answered your question.
Maybe I'll turn it over to Todd to answer your second question.
Hello, Marc. Let me answer your question. As mentioned in my prepared remarks, there are 5.5 million patients 12 years and older that are drug-treated for atopic dermatitis in the U.S. As mentioned, the 5.5 million, approximately 90%, have been cycling on TCS and TCIs, and the majority report that their disease is uncontrolled. If you think about it, by the time patients reach the dermatologist, the majority have already failed one to two topical therapies. These patients, when you talk to them, they're frustrated, and they're yearning for new innovative therapies that will provide that rapid, sustained, long-term disease control, such as Opzelura. We also believe that the dermatologists, that they are well-equipped to understand the box warning for Opzelura and be able to differentiate from the systemic therapies.
As you're aware, dermatologists are very data-driven, and with our medical affairs teams, we will make certain that they are well-equipped to be able to provide clarity relative to this class effect box warning and the value proposition of Opzelura to both alike patients and dermatologists.
Great. Thank you. That was very helpful.
Thank you. Next question today is coming from Tazeen Ahmad from Bank of America. Your line is now live.
Hi. Good morning. Congrats on the approval, and thanks for taking my question. Can you just give us a little bit of color on how we should think about the relative ramp of this indication, let's say, versus Jakafi? You've talked about the $1.5 billion, but for example, should we expect to see any kind of meaningful sales? You will launch in October, but just given all of the language that you provided about payers, should we expect to see meaningful uptake over the next six to 12 months, or is this something that could be much more gradual relative to Jakafi's uptake? Thank you.
Yes. No, thank you for your question. This is Todd. We anticipate during the fourth quarter of this year to have, as mentioned, a higher gross to net due to the higher uptake of the patient support programs and co-pay cards. We would expect that to have an impact relative to revenue generation within the fourth quarter. Thereafter, as we roll into 2022 and are able to secure meaningful access with the payers and reduce the utilization of those programs, that's when we expect the revenue to start to ramp.
Would you be in a position to start providing guidance on sales next year?
At this point, we are not providing guidance. We'll wait to have more visibility on the ramp-up before we are in a position to provide guidance for the year.
Okay. Thank you.
Thank you. Our next question today is coming from Salveen Richter from Goldman Sachs. Your line is now live. Salveen, your line is now live. Salveen, please return to the queue. Our next question is coming from Brian Abrahams from RBC Capital Markets. Your line is now live.
Hi. Good morning. Thanks for taking my question, and congratulations on the approval. Maybe a big-picture launch strategy question. I'm curious how the end label, where there's clear delineation of the itch benefits, but also a lot of these JAK class warnings, overall shapes your detailing strategy in terms of educational approach, types of physicians targeted, and your investment prioritization into this launch. Does your launch strategy assume that the oral JAKs will come to market in AD? Thanks.
Hello, Brian. It's Todd. We do assume that the oral JAKs will come to market. Relative to the launch, as mentioned, we're going to target the high-prescribing dermatologists, the NPs and PAs, as well as the high-priority allergists. As mentioned, these are the prescribers that will be writing the bulk of these prescriptions as we go forward. Furthermore, we have made certain that our team has had a curriculum to make certain that they're well-prepared to be able to bring the value proposition to dermatologists and help them realize the uniqueness and how well-differentiated Opzelura is for patients. Furthermore, and more importantly, as mentioned, we will make certain that our medical affairs team can really differentiate relative to safety, such as earlier within Jim's comments.
To be able to differentiate relative to a class effect box warning versus a unique product box warning, and to make certain that those patients continue to realize, and providers, that full value proposition of Opzelura.
Thanks very much.
Thank you. Our next question today is coming from Kripa Devarakonda Savant from Truist. Your line is now live.
Hey, guys. Thank you so much for taking my question, and congratulations on the approval. One of the restrictions in the label is being able to prescribe it in combination with other drugs, especially given that some or many of these patients may have comorbidities. What sort of impact do you expect to see on prescription trends because of this restriction?
Sure. No, this is Jim Lee, and I'll address that. We don't see it as a restriction
It actually reflects how the study was designed, including the target patient population, the inclusion/exclusion criteria, et cetera. It's essentially how we conducted and designed the studies. We want to test monotherapy, and there's really nothing or no reason to use it in combination with any other therapies for atopic dermatitis. I think that is typically in a clinical practice setting, we're told by physicians that really ideally if patients can just be treated with one product for their disease, for their condition, that's always better than trying to have them treat with multiple products. I don't think it should have a significant impact. Again, we don't see it as a restriction.
Thank you.
Thank you. Our next question today is coming from Vikram Purohit from Morgan Stanley.
Great. Good morning. Thanks for taking my question. I just had one question on commercials. You mentioned that you would expect patients to use three-four tubes per year in AD. I was just wondering if you could speak about how you came to this estimate and what sort of patient profile and frequency of use is implied in this estimate. Also, if at this point you're disclosing how many grams of product is in one tube.
Yeah, thank you. This is Todd. I'll answer that. The amount of grams in one tube is 60 grams. If you think about our pivotal trials within the eight weeks, patients were using that BID and thereafter in a long-term extension it was intermittent therapy. When we look at the utilization of product within the pivotal trials and then give commercial consideration to compliance, we believe that patients on average will use three-four tubes within a year.
Okay, understood. Thanks.
Thank you. Our next question today is coming from Cory Kasimov from JP Morgan. Your line is now live.
Hey, good morning, guys. Thanks for taking my question. Wanted to ask about the language on non-continuous dosing and based on the data you have in AD, not sure it would really have an impact, but curious for any added thoughts there. Do you see read-through to vitiligo, which I believe are longer duration studies? Or is the frequency of use in intermittent dosing very similar with vitiligo as it is with atopic dermatitis? Thank you.
Yep. This is Jim. I'll address your question. The dosing and administration section reflects how the clinical studies were designed. We had basically twice-a-day dosing for eight weeks, and then patients were instructed to stop, and then for the following 44 weeks, they were instructed to treat as needed, meaning if they saw some redness, skin irritation, then they can treat. It's really a patient-focused, patient-directed treatment regimen. That's what's reflected in our dosing administration section in terms of the intermittent dosing. For vitiligo, if you take a look at our clinicaltrials.gov, and hopefully you'll learn more about it later this month. In the phase III vitiligo studies, we tested or had patients treat themselves twice a day continuously. That's the way that clinical trial is designed.
We anticipate that that will be reflected in the dosing and administration section for the vitiligo sNDA label.
Okay. Thank you.
Thank you. Next question today is coming from Mara Goldstein from Mizuho. Your line is now live.
Oh, great. Thank you so much. Just to come back to that last question for a second. To be clear, the intermittent dosing in the label is a function of trial design for atopic dermatitis, not any FDA concerns, as it relates to the other warnings, the class label warnings that are on the label. Secondarily, I'm just curious as to any potential read-through on GVHD, given the chronic nature of that disease, and if you could address that.
Sure. This is Jim, and I'll address your first question.
Okay.
The short answer is no. The dosing administration section was all related to what we designed, what we did in the phase III studies. For the graft versus host disease, perhaps Hervé can address that.
Your question about the intermittent treatment. Jakafi is used continuously in many patients with MF, PV and acute GVHD. We don't see any kind of a connection between the label for the cream is really reflecting the use in the study, and we were expecting exactly what we have, which is the right way to use a product for atopic dermatitis. We don't see any connection with the GVHD indication.
Just in your, I suppose, outreach to physicians, do you think that they understand that the label really reflects the studies as opposed to any outstanding FDA concerns on the oral JAK?
Sure. This is Jim. Maybe I'll address it and perhaps Todd can also comment. I think if you take a look at all topicals, there are very few topicals that are dosed continuously, mostly because patients just can't do that. They stop after they feel better. I don't interpret the dosing and administration as a safety issue or safety concern. We'll obviously clarify that, but I think prescribers, most dermatologists, are well accustomed and used to this type of dosing.
Okay. Thank you. I appreciate it.
This is Todd. Just as a follow-on that indeed, dermatologists do understand that this is the dosing. I will mention that within the pivotal trial, within 8 weeks, these patients, approximately 50% of them rapidly have their itch and inflammation resolved. Thereafter, these patients moved to intermittent therapy during the 44-week long-term study. The short-term and non-continuous chronic treatment very much fits within our study and within our label, and also the way that dermatologists practice with these type of topical medications.
Thank you. Our next question today is coming from Michael Schmidt from Guggenheim Securities. Your line is now live.
Hey, this is Kelsey on for Michael. Thanks for taking our question, and congrats on the approval. How should we think about the line of therapy, kind of given the approved indication in patients whose disease is not adequately controlled with topical prescription therapies? I guess, would a patient need to try and fail topical steroids and topical calcineurin inhibitors? What about incoming topical agents that address non-JAK targets? Thank you.
This is Jim Lee. I can start by answering your question. Maybe Todd Edwards can have some additional comments. Let me just remind you, in our clinical trials that almost 90% of the patients actually had previous therapies, with the vast majority of them with topical treatments. Topical calcineurin inhibitors, topical corticosteroids, even oral medicines. We actually, even though we didn't build that into the inclusion/exclusion, that's essentially what we saw in our clinical trials. I think our label is a reflection of that patient population that we saw. If you think about it, going back to Dr. Eichenfield's slide around the treatment paradigm, most patients really are asked to try with emollients. They typically progress to other topical therapies. It makes sense that they should try topical corticosteroids, which is really the sort of the foundation of most atopic dermatitis treatments.
We don't think it'll have an impact, and in fact, I think it'll select for that patient population that really needs and could benefit from Opzelura.
Yeah, just further, Jim. If you think about the standard of care today, where patients are cycling on TCSs or TCIs, and then there's from there to systemics. A lot of patients aren't eligible for those systemics, nor do they want a systemic treatment. We believe that with payers, that they'll require the patient to fail a topical prior to being eligible for Opzelura. Within that treatment paradigm, Opzelura just fits uniquely in between that topical steroid and the systemics. It's uniquely fitted in there to be able to continue to provide that long-term disease control for patients. I'll just mention this furthermore, relative to our discussions with payers.
They also see this unique value relative to when you look at the long-term disease control of patients, especially with intermittent therapy, and the benefit that Opzelura may have in delaying the time for patients to move on to more expensive systemic therapies.
Great. Thank you so much.
Thank you. Our next question today is coming from Alethia Young from Cantor Fitzgerald. Your line is now live.
Hey, guys. Thanks for taking my question. Congrats on the approval. I just want to talk a little bit about the, you said slide, the 25%-50% gross-to-net. I just wanted to kind of get color on the breakdown between commercial and any other kind of non-commercial breakdown between that number. Also, I wanted to clarify, is that number separate to persistence and compliance assumptions? If so, can you kind of give some color on persistence and compliance assumptions?
Yeah. We're not going to provide guidance at this time during this call relative to gross to net.
Can you talk about the breakout between the commercial versus non-commercial in the market for atopic?
No. If you think about it, the vast majority of patients are commercially insured for atopic dermatitis, just given the age of the patient population.
Okay, thanks.
Thank you. Our next question today is a follow-up from Salveen Richter from Goldman Sachs. Your line is now live.
Good morning, and congratulations on the approval. With regard to your questionnaire and the 15% reduction in prescribing due to the class box warning, can you just provide more color here in whether that reflects some patients won't be appropriate or that physicians don't feel comfortable?
We tested, it was a qualitative research with derms, derm NP/PAs, and those high-prescribing allergists. We proposed to them that if a class box warning was placed on Opzelura, would you or would you not reduce your prescribing of the product? As mentioned, there was a 15% reduction in that prescribing. I think what that tells is that the dermatologists and these prescribers would just want to have a better understanding relative to the class black box and how did that apply to Opzelura or not. At the time, we didn't give that type of detail. It was just more a class box warning.
Thank you. That's helpful.
Thank you. We've reached the end of our question and answer session, and that does conclude today's webinar and teleconference. You may disconnect your lines at this time and have a wonderful day. We thank you for your participation today.