Thank you. Thank you very much for joining out of your very busy schedule today. I'm delighted to serve as MC today. I'm Ikeda from Corporate Advocacy and Relations. Thank you for your time. You can join this meeting through Zoom webinar or live streaming. After our explanation, we will go to a Q&A session. You can ask questions only through Zoom webinar. You cannot ask questions through live streaming. Today, we have simultaneous interpreting in Japanese and English. If you are joining from Zoom webinar, you can choose a language of your preference from the Zoom screen menu. Presentation materials are not posted on our website. If you want to get one, please contact our IR department. Today's presenters are Executive Director, Global Development Project Leader, Dr. Marci English, and Senior Vice President and Head of Medical Specialties, Global Strategic Brand Marketing, Dr. Chema Sanz.
The Q&A session will be joined by Dr. Andrew Krivoshik, President and Head of Development, and Senior Vice President and Head of U.S. Medical Specialties Business Unit, Dr. Lynn Fenicchia. Simultaneous interpreting is available, including Q&A, but accuracy of interpretation cannot be guaranteed. This material or presentation by representatives for the company and their answers and statement in the Q&A session includes forward-looking statements based on assumptions and beliefs in light of the information currently available to management and subject to significant risks and uncertainties. Actual results may differ materially depending on a number of factors. They contain information on pharmaceuticals, including compounds under development, but this information is not intended to make any representations or advertisements, nor provide medical advice of any kind. We'd like to go into the presentation. Marci, the floor is yours.
Thanks, Hiro. Thank you to our audience for joining us today. Next slide, please. I'll skip reading this again because our cautionary notes were read by our moderator. Next slide, please. Today, we're giving two distinct presentations. First, I'll provide an overview of all of our data presented at the North American Menopause Society Annual Meeting in Atlanta, Georgia. I'll turn it over to Chema Sanz, our Senior Vice President and Head, Medical Specialties Global Strategic Brand Marketing, to speak about our extensive market research and how those insights are being used to educate both HCPs and women about VMS. As a reminder, VMS stands for vasomotor symptoms, otherwise known as hot flashes and/or night sweats, and are the most common and bothersome symptoms of menopause. Next slide, please.
We have generated an extensive amount of data to support the safety and efficacy of fezolinetant, our novel investigational selective neurokinin 3 receptor antagonist. We were excited to present this data at NAMS. There's significant interest in the SKYLIGHT 4 study, and we appreciate you taking the time to learn more about the encouraging results. In addition to the results of SKYLIGHT 4, I'll also briefly summarize our other congress presentations, including three that highlighted pooled efficacy data from the phase III SKYLIGHT 1 and SKYLIGHT 2 studies. We also had three U.S. real-world evidence presentations, which examined the association between VMS and weight gain, sleep, and work. Next slide, please. The primary objectives of SKYLIGHT 4 were to evaluate the safety and tolerability of fezolinetant and its effect on endometrial health over 52- weeks.
The primary endpoints were percentage of women with endometrial hyperplasia, the percentage of women with endometrial cancer, and the frequency and severity of treatment-emergent adverse events, or TEAEs. Next slide, please. As previously disclosed, SKYLIGHT 4 is a randomized, placebo-controlled, double-blind study, phase III, 52-week long-term, and this is primarily a safety study. Looking at fezolinetant 45 mg, fezolinetant 30 mg, or placebo once daily with a randomization schema of one to one to one in each arm. In women aged 40-65- years of age inclusive, who were seeking treatment for VMS associated with menopause. Next slide, please. This slide describes the participant disposition, and you can see that 1,831 women were randomized, and 1,830 took at least one dose of medication.
As you can see, the participants were equally distributed among the three treatment arms. Of the number of women enrolled, 599 met the criteria for the endometrial health set, which required endometrial biopsies to meet the pre-specified criteria consistent with the FDA draft guidance for industry dated 2003. Next slide, please. With regard to demographics and baseline characteristics, these were balanced among the treatment groups. Approximately 80% of participants were White, and 17% were Black or African American. The mean age of the participants was approximately 54. Approximately 17% of participants were previously treated with hormone therapy, and about 18% had a prior surgical hysterectomy. Next slide, please. Treatment emergent events were similar for both fezolinetant and placebo. The incidences of TEAEs and TEAEs leading to discontinuation were similar across the groups, and there was a low incidence of serious TEAEs.
One death was reported in the fezolinetant 30 milligram group, and it was unrelated to study drug. Next slide, please. The majority of TEAEs were mild to moderate in severity, and most frequently reported events defined as greater than or equal to 5% were headache and COVID-19. Next slide, please. Elevations in transaminases were low across all groups. As you'll see on this and the following slide, we see that low incidence. The elevations were generally asymptomatic, isolated, transient, and resolved on treatment or soon after discontinuation of treatment. Elevations of ALT or AST more than three times the upper limit of normal were observed in six participants who received placebo, eight who received fezolinetant 30 milligrams, and twelve who received fezolinetant 45 milligrams.
Overall, 8 participants had ALT values more than five times the upper limit of normal, and the distribution of those particular patients was similar across the treatment groups. Importantly, with regard to the patient experiencing eight times the upper limit of normal in ALT, this patient was receiving placebo. AST values more than five times the upper limit of normal also had a similar distribution across the treatment groups with an overall low incidence rate. Once again, it's important to note that the frequency of these elevations in AST and ALT were generally asymptomatic, isolated, transient, and again resolved on treatment or soon after study drug discontinuation. In general, the cases of increased liver transaminases were not concurrent with COVID-19 infection. Next slide, please.
Before we get to the analysis of the primary endpoints supporting endometrial safety, an important secondary endpoint was to evaluate the changes in endometrial thickness. What you can see here is that the mean change in endometrial thickness from baseline was similar across the groups. Next slide, please. Moving on to the primary endpoints of endometrial safety, fezolinetant met the FDA predefined criteria. The rates of endometrial hyperplasia, cancer or disordered proliferative endometrium were evaluated separately. The defined threshold for establishing endometrial safety is specified by the FDA and requires demonstrating rates of hyperplasia or malignancy less than or equal to 1%, with an upper bound of the one-sided 95% confidence interval for that rate that does not exceed 4%. Endometrial hyperplasia was observed in none of the women receiving placebo or fezolinetant 30 milligrams and one woman receiving fezolinetant 45 milligrams.
As you can see from these point estimates and the confidence intervals, fezolinetant met the a priori defined requirements for demonstrating endometrial safety. Criteria for demonstrating endometrial safety. Next slide, please. In conclusion, the SKYLIGHT 4 data demonstrate the 52-week long-term safety and tolerability of fezolinetant as studied and support its continued development for the treatment of moderate to severe VMS associated with menopause. Next slide, please. I'm now going to speak briefly to the additional analyses of our pivotal pooled efficacy data from the phase III SKYLIGHT 1 and SKYLIGHT 2 studies presented at NAMS, which focused on early response to fezolinetant, sleep impact, and treatment response analyzed by race.
The first pooled analyses presented assessed early response with fezolinetant, and a trend in improvement in mean change from baseline in daily moderate and severe VMS frequency versus placebo was seen from day one of treatment. This is very encouraging data. We also know that VMS can be disruptive to daily life and interfere with sleep, among other negative impacts. The next analysis assessed the effect of fezolinetant on patient-reported sleep disturbance using pooled data from SKYLIGHT 1 and SKYLIGHT 2. The pooled data further demonstrate the effect of fezolinetant on three measures of patient-reported sleep disturbance as early as week four of treatment. Lastly, while examining our data, we also saw fezolinetant demonstrate superiority to placebo across various subgroups. An important pre-specified analysis investigated the efficacy of fezolinetant in Black and non-Black subgroups as self-identified, again using the pooled data from SKYLIGHT 1 and SKYLIGHT 2 .
This is important because we know from other research that the burden of VMS is known to be higher in Black women. The pooled data indicated a trend towards higher VMS frequency at baseline for Black women compared with non-Black women. Our data indicates that fezolinetant was efficacious at week four and was maintained through week- 12 in both Black and non-Black populations. Next slide, please. As I mentioned previously, we know from other research that VMS can be very disruptive to daily life at home and at work, contribute to anxiety or depression, and interfere with sleep, relationships, social activities, concentration, energy, sexual activity, and overall quality of life. These next three real-world studies we presented at NAMS continue to add to our general knowledge of how VMS impacts women. The first study was an online survey that evaluated the association between self-reported VMS severity and sleep quality.
The vast majority of women, and almost all those with severe VMS, said that VMS had a detrimental impact on their sleep. Not surprisingly, as VMS severity increased, sleep disturbance and sleep-related impairment rose and sleep quality worsened. Poor sleep quality linked to VMS associated with menopause is a major challenge for women, as we'll also see in the next study. This study evaluated the association between VMS severity and work productivity in women with menopausal symptoms. The data show that VMS severity is associated with the degree of impairment in daytime activities and work productivity, and that VMS associated with menopause commonly disrupts sleep, which in turn affects daytime productivity. This last study, which was presented in an oral session, aimed to quantify the extent to which changes in VMS frequency are associated with subsequent weight gain in midlife women.
Importantly, this study provides the first evidence that VMS, including increases in VMS, onset of high-frequency VMS, and persistent VMS, may be independently associated with weight gain among midlife women. However, these findings highlight the need for further research, for example, to clarify the potential mechanisms linking VMS to weight gain in midlife, and may inform appropriate counseling about health risks and potential interventions for women with VMS associated with menopause. Next slide, please. We're encouraged by the results thus far and the growing body of clinical evidence to support fezolinetant. The BRIGHT SKY clinical development program was designed to provide comprehensive insights into the safety and efficacy of fezolinetant, with a clear strategy for gathering patient-reported outcomes to capture women's experiences.
One important factor that I want to highlight today, these studies, SKYLIGHT 1, SKYLIGHT 2, and SKYLIGHT 4, recruited faster than ever and during the COVID pandemic, and we maintained high rates of patient retention across all studies. This was a remarkable accomplishment and something that I haven't seen in my nearly 30- years of working in the industry. It also suggests that women want treatment, and there is an existing unmet need for safe and effective non-hormonal treatment options. Ultimately, our goal is to secure regulatory approvals so that we can advance care for women who experience moderate to severe VMS associated with menopause. Now, I'd like to turn it over to Txema Sanz to take you through what Astellas is doing to help educate about VMS in the United States. Txema .
Thank you, Marcy, and thank you, all of you again, for joining this meeting. I am really excited to talk to you directly today because we have a real opportunity to help millions of women worldwide who are suffering from VMS. Today, I'll share with you some insights from over five years worth of market research, as well as the details from our disease education activities. Now, the three topics I'll tell you about in more detail in the coming slides are, firstly, market research showing how large this opportunity to help millions of women worldwide with VMS is. Secondly, I'll talk to you about why women are highly motivated to seek solutions. Thirdly, I'll talk more about what Astellas is doing to help educate both healthcare professionals and women. Next slide, please.
If you look at the global picture, you'll see that there's an estimated 1.2 billion women that will be peri and post-menopausal by 2030. No matter where you are in the world, millions of women are suffering from VMS associated with menopause. We know that VMS are the most common symptoms of menopause for which women seek treatment. They occur in up to eighty percent of women aged 40-64, and they persist for a median of 7.4- years. You'll see across the different countries, it's a slightly different picture, but there is a commonality in that many individuals cannot take or choose not to take hormone therapy. As a result of that, there's been a steady decline in the use of hormones across most of these markets.
Now if we drill down specifically and have a look at the United States. If you can go to the next slide. In the U.S. alone, the total number of hormone therapy patients from 2000 to 2021 has declined by 75%. Now we calculate that approximately 25 million women were taking hormone therapy in the year 2000 in the United States, and now there's less than 4 million. Really what this demonstrates is that many individuals chose not to take hormone therapy, or they cannot take hormone therapy. Next slide, please. Again, looking at the United States in a bit more detail here. More than 30 million women between the ages of 40-65 are postmenopausal. Now, among them, more than 10 million of them are experiencing moderate to severe VMS associated with menopause.
Yet more than 61% of these women experiencing moderate to severe VMS cannot or choose not to take hormone therapy and are thus seeking other treatment options. Next slide, please. As I mentioned earlier, the second point we're gonna talk about now is the healthcare professionals and insights that we have from market research and the women's insights. First of all, looking at healthcare professionals. We've interviewed more than 6,000 doctors, actually, and more than 8,000 women experiencing VMS over the last five years. First of all, I'm just gonna share with you three key insights we learned about doctors in the United States. Doctors' knowledge of the mechanism of VMS is very low. 80% of doctors are unaware of how VMS works, particularly the role of the KNDy neuron.
Secondly, doctors don't feel educated on menopause or VMS associated with menopause. We also learned that 80% of OB-GYNs receive no training in menopause medicine, and only recently has menopause been included in medical school curricula in the United States. Thirdly, doctors want alternatives to hormone therapy. They've told us in market research that only 26% of doctors are very satisfied with current treatment options. Even worse, 35% of doctors feel powerless in helping patients because they perceive there isn't a safe and effective VMS treatment. Doctors want alternatives to hormone therapy. Next slide, please. Now we're gonna focus in on the market research insights from women. As I mentioned to you, we've interviewed over the last five years, more than 8,000 women across the globe experiencing VMS. There's four insights I'd like to focus on.
Firstly, 90% of women indicate their experience with VMS is significantly worse than they expected. As you'll see from these different testimonials from different countries, these are the words of women and how they express the impact and the burden of VMS on their lives. Secondly, VMS are the most common symptoms of menopause for which women seek treatment. They occur in about 80% of women aged 40-64, and they persist for a median of 7.4 years. Thirdly, we know from this research that women are highly motivated, yet misinformed and frustrated by the information they get. For me, the key takeaway from all of this is that women want alternatives to hormone therapy. We see this in research. We see this in what's happened with HRT usage over the years. This is really the key insight.
They want alternatives to hormone therapies. The biggest complaint from patients is a perceived lack of treatment options that are both effective and safe. If we go to next slide, please. Building on these powerful insights, last year in September, just over a year ago, we successfully launched our first multi-channel doctor disease education program to help further doctors' awareness, their understanding and perceptions of VMS. We launched a website called KnowVMS.com, which is what's displayed on the screen right now. We also have 500 employees in Astellas delivering disease education materials. This is all in the United States at the moment. 500 employees delivering these disease education materials.
Now, the education content is factual, credible and dynamic, and I'm really thrilled to say that the response has been overwhelmingly positive so far, and we're seeing already very high levels of engagement with our educational materials. To date, we have reached 132,000 doctors and counting. Based on the feedback, doctors' awareness and appreciation of the burden of VMS on women and of the newly understood mechanism of VMS is increasing. Of course there are more education gaps to fill. For example, doctors do not fully understand that women of color experience VMS at a higher than average prevalence, as Marcy already mentioned. We're contributing to provide educational materials focused on the epidemiology of VMS included in these subpopulations.
Secondly, while awareness and understanding of VMS is improving, there is still a need for further education on the negative implications and burdens of VMS on women. As we move forward with our efforts, we'll continue to provide you with further updates on these educational programs. Now if we go to the next slide. I've told you about our education activities in doctors, the previous slide, and now I'm gonna tell you about our education activities for women. Now, this has only just started. We started this program in August. This is very new information, but very excited to share it with you today. In August, we began our disease education activities with women, and we've already reached 257 million impressions with the content through the end of September.
Now, our educational activities include this, recently launched website called whatsvms.com, which is what you can see here on this diagram or this picture. What we are aiming to do is educate women around these symptoms and validate what they've been experiencing is a medical condition called VMS and encourage them to speak to their doctor about VMS. Now, I'm pleased to say that we've already had 284,000 visitors to the website since launch. As I said, this has only just launched. Once again, the educational content is factual, it's credible and highly engaging. For example, we are collaborating with endemic health websites that you'll know about to ensure that VMS education is included where it didn't exist before. The endemic healthcare website examples are websites like WebMD and the Mayo Clinic.
We also have some initial data on our video completion rate for those on YouTube with other endemic partners, which is already 80%. What that means is the video content we're using is watched from start to finish by 80% of the people opening them. That's really high and very much validates the high engagement of this group. We're also working with digital opinion leaders to further educational gaps in knowledge and care through their own social channels. For example, TikTok. This is a platform where the 40-49 and the 50+ demographic have grown exponentially, and it's a very interesting channel for us to educate. It's the first time Astellas is using TikTok, but we're already seeing very high interest and really good initial results.
Now, as I said, we're just starting here since August, but we are launching now in the coming months, further disease state education through broad-based media. Ultimately, our goal is to provide educational content to 90% of women aged 40-65 by the end of this fiscal year. We go to the next slide, please. Thank you. Finally, at the core of all these educational efforts sits the ability to help doctors and millions of women to fully understand VMS and to be able to have a more constructive dialogue about VMS, which is a real medical condition worthy of attention. We've got the utmost confidence in our efforts and ability to educate based on what I've already showed you in our educational campaigns.
As we continue to progress, we're really looking forward to share with you more detailed updates as we go along. We'd like to thank you for your attention and at this time, we'd be very happy to answer any questions you might have. If I can hand back to Hiroki Ikeda, and he can moderate. Thank you.
Thank you so much. That's all the presentation we have prepared. Here we would like to entertain your questions. The questions are accepted only through Zoom Webinar. You cannot ask questions through live streaming. You can ask questions in Japanese or in English. Toward the bottom of Zoom screen, you can find the icon for raising a hand, so please use it. For those from smartphone, please tap the details and you can find the raise your hand button. If your name is appointed, then on your screen, please unmute yourself and mention your name and affiliate, then start your question. This fezolinetant is still before the approval. Therefore, today, when it comes to the sales strategies or price strategies, the answers might not be sufficient. Please do understand that.
After the post-approval, we are planning to have another, this kind of session. When it comes to the sales strategies, please wait for a moment for the details. Now please start the question.
Hi.
Thank you for waiting. First question, Nomura Securities, Mr. Kohtani, please. Kohtani from Nomura Securities, can you hear me? Yes.
Questions in English. First of all, congratulations for the wonderful data. I think there is, as you may know, a big disconnect between what the market thinks about fezolinetant and I think Astellas' estimation of the fezolinetant's market potential. One of the key information we were missing is how quickly the drug works, sort of a wow factor for doctors and patients. The most effective treatment, I think hormone treatment for now, I think takes a few weeks to work. I'm trying to actually figure out what other drug in women's health works on the first day, because I think this is very important as an impression on, you know, how effective this drug works. If you could, I don't know if you could give us an idea of how this profile of fezolinetant could be an advantage for quick uptick. That's the first question.
Thank you very much.
Thank you very much. Marcy is going to talk about from the perspective of science and commercial perspective. Txema is going to give you the answer.
If I understand your question and statement correctly, yes, fezolinetant, as you saw from the data today, works as soon as one day after taking. Of course, that's a mean or an average. As it relates to other therapies, the only thing I can reference would be the clinical guidelines, for example, the NAMS clinical guidelines. They state that hormone therapy takes anywhere from three to six weeks, I believe. But certainly those guidelines would provide the benchmark for the expectations of hormone therapy. Chema, I'll let you address from a market perspective.
Yeah. Thank you. I think the question also touched upon the uptake and the potential of the product. I think if we start by looking just to look at the size of the market. As I mentioned, there's 1.2 billion women globally that are postmenopausal by 2030. In the United States alone, that's 30 million women of the ages 40-65. We know that 25 million women were taking HRT in the United States previously, and now it's only 4 million. That clearly shows that there is a big potential here to address these symptoms because of this population, 10 million we estimate or greater than 10 million women experience moderate to severe VMS. The key point is women want an alternative to hormone therapy.
Our research also confirmed this because 79% of women state they would likely talk to their doctor in the future if a novel, non-hormonal treatment option were approved and available. These facts, the market potential, the high burden of symptoms on women and the high motivation of women to seek treatment, if it's a non-hormonal treatment, these facts give us really, make us very confident in our uptake assumptions and peak share, peak sales share. Maybe if I can, I'd just like to invite Lynn, our head of U.S. marketing here, just to say something more about what's happening in this chart here in the United States.
Sure, Chema. Thank you. I would be glad to. Good morning, everyone. Again, as Chema mentioned, when you look at this graph, and these are patients in the United States specifically. At one time in the U.S., roughly 25 million women were on hormone replacement therapy. The utilization of that treatment option of the past has declined dramatically by 75% in the last two decades. The reasons for this, what we've learned in research is for a lot of women, they don't want to take HRT or it's contraindicated or simply HCPs do not want to prescribe it because of the concerns. This leaves a major gap in treating these symptoms for women. Again, I'll reiterate from a U.S. perspective the opportunity, and there's really four points to contemplate here.
First of all, there are a lot of women in this patient population. In the U.S., there are more than 10 million women experiencing moderate to severe VMS symptoms associated with menopause, and that's exactly the indication that we are seeking. Secondly, we know that these symptoms are bothersome. In our market research across more than 8,000 women experiencing VMS, we've learned that 90% of these women indicate that their experience with VMS is significantly worse than they expected. Third, as I just mentioned in the graph here, the utilization of the treatment option of the past, which was HRT, has declined dramatically. Then lastly, we know that these women are highly motivated to seek options, which is critical to our success.
you heard from Marci that in our clinical trials, the rate of enrollment of these patients exceeded our expectations, and this was at the start of COVID. that's been validated in our research across 8,000 women. 79% say that they would likely talk to their physician in the future if a non-hormonal treatment option were available. that's eight out of ten of the women that we spoke to said that they would talk to their physician if they learned of a non-hormonal treatment option. for all of these reasons, we feel very optimistic about the potential of this product in the United States to help women.
Thank you, Shinichiro Kohtani.
Thank you for the answers. Just the second question is, I know I'm very aware of Astellas' very extensive research on VMS patients. I think you guys have published on multiple publications. I think the one that stands out is the one from Maturitas in 2022. I see the papers show 12% of patients are contraindicated for hormone therapy due to cancer, heart attacks, liver problems, etc. Another 49% of women, I think, require caution to use hormone therapy due to smoking and diabetes, family history of breast cancer, etc. Can we assume that the uptick in that 12% that is contraindicated for hormone replacement therapy, that uptick will be pretty quick?
What I'm struggling to understand is how should we think about the uptick in the remaining 49% who are cautious, you know, I guess require caution to use hormone therapy? That's the second question.
Thank you for the question. First, Chema, please.
Thank you so much for this question. Yeah, you're absolutely right. There are different populations of women that either cannot take hormones or choose not to take hormones. The paper you're referring to is a review of chart records of patients that already present to doctors. I think the figure that is most striking to me in that paper is that over 61% of women who present to a doctor choose not to or cannot take hormones, over 61%. You know, that's composed of contraindicated patients, as you said, about almost 12%, patients that have pre-existing medical conditions or risks like cardiovascular risk or other such risks, 49%. Overall, women who are averse to taking hormones is 57%.
There is a large number of women who want an alternative, who are already presenting to doctors. These are all potential women and targets that could benefit from another therapy. This is not the whole market. If we go to Slide 19, please. You see this paper refers to patients that were already presenting to doctors, but there is a huge group here that don't even go to see doctors, and these patients will also start to go and see doctors. As I think myself and Lynn mentioned in our research, we saw that 79% of women that we researched with moderate to severe VMS symptoms associated with menopause said they would go and seek medical treatment if there was a non-hormonal alternative.
That's another big group that is in addition to the groups that I've spoken about already. I hope that answers your question. Please let me know if there's anything else.
That does perfectly. Third and last question. Just so safety data checks out, you know, I think the, you know, the biggest concern of course is the effect on endometrial thickness and effect on cancer risk. But I think as you explained, it met FDA's predefined criteria of endometrial safety, so that should probably be okay. The only thing remaining is the doubling of the greater than three times the upper limit of normal liver enzyme levels as compared to placebo in the Fezol 45 milligrams. And I think there was an increase in the Fezol 30 milligrams also. Now I understand the Hy's Law was not met and looks like no bilirubin changes also. This basically can be interpreted as a temporary rise, not really a significant, you know, something that would require caution from the FDA. That's my last question.
Okay. Marci, could you take this question?
Yeah. I missed the very first part of your question, but I believe it was you were commenting on the incidence of ALT or AST and whether or not this was transient. As I stated in the presentation. Our analysis of this data, these elevations were asymptomatic, they were transient, and in many cases, they stopped while patients continued taking therapy or soon after discontinuation of therapy. As it relates to the FDA's evaluation, we have worked diligently to provide a robust analysis of this data and we look forward to the FDA's review.
Thank you. Again, congratulations to all the data. Thank you.
Thank you, Kohtani-san, for your question. Next, Mr. Yamaguchi from Citigroup Securities, please.
Can you hear me?
Yes.
Thank you. This is Yamaguchi from Citigroup. I have two quick questions. The first question is you mentioned about several patient awareness programs, including TikTok or SNS. Given in the past, the patient awareness program was focused on the so-called TV program called DTC, and we've spent US dollar millions and millions in the past. In general, is it fair to say that those ways to increase their patient awareness has been changed because of those SNS era? Also, is it fair to say that you can do this kind of thing relatively in a cheap manner compared to just a big DTC campaign, which we saw back in the 1990s or early 2000s? Thank you. That's the first question.
Thank you, Yamaguchi-san. Chairman, could you take this question?
Yeah. Thank you very much for the question. I'm gonna hand to Lynn in a minute, moment, and who will give you more information. Just allow me to say a couple of things. We've started this campaign, the DSE education campaign, using different channels, digital channels, Omnichannels, and so on, as I've mentioned, and some innovative areas like TikTok. Our plan is to engage with large multimedia television advertising from October. That would also be the case come when we, you know, if the product is successfully approved. Because it's very important to have a mixture of channels and the TV channel has the broadest impact on the number of patients more than any other channel.
Because if you remember, we have to target, you know, 30 million women in the United States.
Mm-hmm.
That's a big audience. I'd like to ask Lynn. Lynn is the expert here and perhaps can give some more opinion.
Sure. Txema . Yeah. Thank you very much. I mean, I'll answer this in two ways. First, just looking at our reach to date in reaching women. As Txema mentioned earlier, we just launched our DSE campaign for women specifically in August. It's new, but we're seeing very strong engagement. After just a month or two, we've had almost 300,000 visitors to the website. Our video completion rate is 80%, which means these patients are listening to the videos from start to completion at 80% of them. This is just one month into the campaign, and it really confirms everything we've learned about how women want to engage around this disease state awareness.
Now, we are going to be launching a TV campaign for disease state awareness later this month. We're really excited about that. As Txema said, we will launch with a variety of channels for direct-to-consumer advertising. By and large, TV will be incredibly important because of the 30 million women that we need to reach. We will be launching with a direct-to-consumer campaign on television.
Mm-hmm.
I'd also like to note that we have a tremendous amount of experience and expertise at Astellas with direct-to-consumer advertising going all the way back to the launch of VESIcare in 2004, which relied heavily on direct-to-consumer advertising, as well as our on-market brand currently with Myrbetriq, where we advertise on TV as well. This experience that we have in this area will be extremely relevant with VEOZAH because we believe it will be a heavily consumer-driven brand. Thank you.
Thank you. A quick second question, please. I think you used to have clinical trials run on the 30 mg and 45 mg. My understanding that you file only for 45 mg to the agency at the moment. Given the balance of efficacy and safety, I thought that some patient might want to take that low dose first, then goes to the high dose in the future because they want to check the efficacy. You seem to go the 45 milligram one dose. Is this situation may change your strategy or it's not really? Thank you.
Marci.
Marci.
Marci.
Yes. Yes, I can answer that question. As you state, we have filed with the 45 milligrams as our dose for potential approval. In evaluating the efficacy data and the safety data, Astellas feels that this provides the best benefit-risk balance for patients. We look forward to the agency's assessment of the totality of our data.
Okay, thank you.
Thank you for your question, Yamaguchi-san.
Next, Mr. Hashiguchi from Daiwa Securities, please.
I'm Hashiguchi from Daiwa Securities. Thank you for this opportunity. Patient-reported outcome. What kind of data do you have in terms of patient-reported outcome? Could you elaborate on that? This time at NAMS, you had presentations, I'm sure. In the presentations at NAMS, new treatment is being awaited by many patients, as you said. Fezolinetant can meet the expectations of such patients. Does it have such efficacy to respond to their expectations with HRT? Not only VMS, but other symptoms can improve, and patients can really feel the benefits according to my understanding. Patients who initiate fezolinetant treatment would be satisfied, it will lead to the continuation of their treatment because of the high efficacy. Please explain.
Marcy, could you please respond to this question?
It's a wonderful question because as we designed this program, one of the key aspects Astellas was very focused on was certainly reductions in frequency and severity are important. We need to demonstrate that to the regulators. But in addition to reducing that frequency and severity, we needed to also focus on what's important for patients. You know, at NAMS, we presented some very interesting data on sleep in our pooled analyses across SKYLIGHT 1 and SKYLIGHT 2. In those trials, in those pooled data and in both of those studies, we implemented three independent measures of sleep. We used the PROMIS-SD short form, which is a sleep disturbance form, and we also used two patient global impression scales.
One, a Patient Global Impression of Change scale, and another, which was a Patient Global Impression of Severity scale. What that analysis showed was that across these 3 PROs, and I'll mention that the PROMIS-SD doesn't just look at kind of a global assessment. It's not a single question. It asks about specific aspects of sleep and comes up with a total score. Across all of these three independent PROs, we saw a benefit. Women reported a benefit in their sleep as their VMS declined, and that's saying, of course, to fezolinetant to get those VMS episodes to decline. We also analyzed the MenQoL, for example. We have some manuscripts in press or in preparation, rather, looking at menopause-specific quality of life.
We'll be hopefully publishing that in the near future. I think, you know, to just round out your question about whether or not, you know, patients are getting this benefit. I'm gonna bring you back as well to the fact that we had such high patient retention in these trials across the pandemic. Women still came into the office as they were able, still answered the patient-reported outcomes, and stayed on fezolinetant. I think that in and of itself demonstrates that patients are receiving a clear benefit from taking fezolinetant as it relates to quality of life.
Thank you very much.
Thank you so much. That's all from me.
Thank you. Next, Morgan Stanley MUFG Securities. Mr. Muraoka, please.
Good morning. I'm Muraoka from Morgan Stanley. Can you hear me?
Yes. Thank you.
The market price matters. Well, I've heard you cannot go into the details now, but let me ask you about this. Your approach for the future reimbursement or insurance coverage, this is mainly covered by the private insurance, but with the pricing, if in order to get the appropriate positioning, what should be the focus? The price, data? I think those are important for the positioning for reimbursement of the insurance coverage. It's okay if it is still abstract, but is there something that you can share with us? Thank you very much. Chema, I think that there's a certain restriction for the disclosure of the information, but as much as possible, could you answer this question?
Thank you. Thank you very much for the question. As you stated, I can't go in to discuss specifics around price because it's an unapproved medicine. However, I would say that the pricing policy for us will be the same as with our previous assets. That won't change, and that we will strive to obtain a price that reflects the value that this drug would bring to patients, to healthcare systems and also to society, obviously. That would be in terms of policy. What I would also say is that we are very well-advanced in our planning for all the market access situations we encounter ourselves around the globe in the big markets.
I think you asked a particular question perhaps pertaining to U.S., so maybe Lynn, you can give some further comments on the access situation and whether it's the commercial market or otherwise in the U.S.
Yes, I'd love to. Chema, thank you very much, and thanks for the question. This is very relevant. We do anticipate that the patients that will go on fezolinetant will predominantly be commercial payers. We have a lot of experience in this area in dealing with the payers in the United States. With our on-market brands, we've been able to secure a very broad coverage due to the expertise of our account team. We're spending significant amounts of time right now evaluating the marketplace. We feel very confident of the plans that we have in place to address access. We plan on launching a very comprehensive patient support program to facilitate access for patients.
In fact, I would say in my 19- years at Astellas that we will be launching with the most comprehensive patient support program that I've seen to date. We want to make sure that patients have access to this medication. We're also the last thing that I'll say from a U.S. perspective is we are learning that payers want to make this condition a priority. We've conducted market research. We talked to you a lot about our market research conducted with HCPs as well as with women. We're also conducting market research with payers specifically so that we could learn, and what we've learned is they want to make this condition a priority.
We've been having pre-approval information exchange discussions with payers, and in more than 20 conversations recently, fezolinetant continues to generate interest, and it generates positive perceptions, and it's being seen by these payers as a necessary non-hormonal option for a very high unmet need in their current membership populations.
Thank you, Lynn.
Mm-hmm.
Thank you so much. One more question. 30 million women you have to reach in the United States. Astellas alone can cover 30 million women on your own, or in the end, you have not ruled out the possibility of working with a potential partner. How should I think about it? Chema, please.
Thank you very much for the question. Thirty million women are the potential target, and of those 30 million women, 10 million women are the likely population that we would obtain a label for. Of course, we haven't got a label yet, so that remains to be confirmed by FDA. But 10 million women is our working assumption. Now, the way to target and reach those women is through a fully integrated multi-channel campaign, including television, social media, and all those channels that we've been speaking about. We are very well served, and I think we have a. You know, I've reviewed the plans in detail with the U.S. team, and they have a really comprehensive plan to reach those women.
Yeah, I feel very confident that those plans are gonna be successful.
Chema, I guess Muraoka-san's question is linked with more like a potential option for the partnership or not.
Sure. Well, we always keep our options open in all strategic scenarios. In the United States, we have assessed the landscape, and because of the capabilities we have that Lynn mentioned, we believe that we're in a very strong position to maximize this opportunity ourselves in the United States.
Thank you.
Chima, I would just add on to that we have done a lot of research with the appropriate deployment model for fezo in terms of the sales force size and even structure. I'll just go on to say we haven't really talked about the capabilities of our sales force yet, so I will add a little bit of perspective here. First and foremost, we believe that being first to market offers a significant opportunity. We have a great responsibility being first to market to bring this solution to women that are in need. Also we have a very experienced and knowledgeable sales force. They're experienced in primary care as well as OBGYN, which are the two predominant markets that we will be targeting. We have experience.
Our sales force has sold products predominantly prescribed to women in the past. If you look at VESIcare and Myrbetriq.
Those are heavily prescribed to women, and they're prescribed by PCPs and OBGYNs, the same target audience that we will be targeting for fezo in women's health. Not only have they been selling these products and selling Myrbetriq today, they have brought both of those products to branded market leadership with tremendous success. For all of these reasons, we feel very confident that, while we will always keep various options open, that we can do this without a partner, because of our sales force capabilities, and again, we have researched and are deploying the optimal model.
Thank you very much. That's all for me. Thank you.
Thank you. Next, Mitsubishi UFJ Morgan Stanley, Mr. Kumagai, please. Ms. Kumagai, please.
Can you hear me?
Yes.
The competitors to market supplement for post-menopausal women in the States, American women tend to prefer supplements to prescription drugs to treat some of the symptom, including VMS. Do you think it's simply due to lack of safe and effective treatment in the States, and fezolinetant will change the patient behavior? That's my question. Thank you.
Thank you, Kumagai-san. Let Chema to take this question first, and if needed, hand over to Marci.
Could you just? I think I certainly missed the first 10 seconds of the question. Was it related to a-.
To super-.
Yeah.
Yeah, super.
U.S. market. Yeah, the supplement. Yeah, one of the Japanese company markets supplement specifically target postmenopausal women, and they say that American women tend to prefer supplements. You know, my question is once fezolinetant gets approval, is that gonna change the landscape of the market?
Yeah. Thank you so much for the question. Obviously, I won't comment on Otsuka's product or strategy. That's not really my place. I would say, first of all, overwhelming reaction is positive. I'm very pleased to have that women have more options in the market. I think this is great that other companies and are entering and providing women's different options. I think that's the first and most important point here. That's good news. I think in terms of the marketplace as we see it, there are obviously different segments in the marketplace for nutrition and supplements compared to prescriptions. What I would remind you is 25 million women chose HRT in the United States, and I think that's the most important kind of fact to base this on.
As I say, you know, our view is that this marketplace presents you know, a very substantial opportunity to fezolinetant.
Understood. Thank you. My second question is, the profile of the compound. If I remember correctly, Chinese studies are not successful. Can you talk about ethnic difference, of this compound? Thank you.
Thank you. Marci, could you take this question?
Of course. I believe you're referring to the RATIONALE-305 study, which we announced the results of not too long ago. We are continuing to investigate that data to try to understand the outcome. I think what is important to remember is that when you look at the 30 milligram arm for fezolinetant, we saw a response that was very similar to what we saw with 30 milligrams in SKYLIGHT 1 and SKYLIGHT 2. I think you know what we really need to do, as I noted, is continue to investigate that data to try to understand why we saw that difference. We did see a pronounced placebo effect in that trial. Why we saw that effect is still, again, under investigation.
I think it's very important as well, just as a reminder, we did not test 45 milligrams in that study. That was a two arm study testing placebo versus 30 milligrams fezolinetant. It's an important aspect to keep in mind when you think about the China study.
Okay. Thank you so much.
Thank you very much.
Thank you so much. Next, J.P. Morgan Securities, Mr. Wakao, please.
J.P. Morgan. Wakao is my name. Thank you very much. First question is about the safety. Fulfill the criteria by FDA. From the approval perspective, I do not have any questions, but the data for the thickness of the endometrium, that is Slide 12. If we look at this, FDA criteria is satisfied, but on the other hand, fezolinetant arm, if we look at the change width is bigger. This fact might have impact into the real world. Isn't it necessary to assume in that way? That's the first question from me. Thank you very much.
Then Marci, could you answer?
Of course, I can. Just to be clear, endometrial thickness was a secondary endpoint in our trials. It is not an analysis that factors into the criteria which we need to satisfy in order to demonstrate endometrial safety. I think what's important when we think about endometrial thickness in looking at this data on this slide is that decrease in the lining of the endometrium is a natural result of aging. What the FDA and other regulators and clinicians would be concerned with is if we saw a pronounced increase in the thickness of the endometrium. I think what we see in this data here is that we see a normal age-related decline, which is similar across the treatment groups. I don't think we anticipate any negative review of this data from the perspective of the regulators or clinicians.
Thank you. Secondly, the guideline in the United States and also the possibility of inclusion into the U.S. guidelines. In this field, how important the guideline is in this field? Fezolinetant I think will be included in the guidelines into the future. When that timing is going to be? Hormone therapy is now a gold standard, and when fezolinetant would exceed hormonal therapy, and it must be a gold standard into the future by exceeding the hormonal therapy. What about that possibility?
Maybe we should ask Marci or Chema. I don't know who I should send this question to. First, Marci, please.
Sure. As you stated, I want to be very clear. You know, we've recently just presented this data at NAMS and at other conferences. We are still not an approved therapy, and I do think it will take time for guidelines, for clinicians and for societies to review this data. What I can say is I was at NAMS last week, and I believe that this data is being received very positively. I don't think that there's a clear answer to your question about predicting. We can't really predict the integration of fezolinetant in a future approval state and the timeline for those guidelines. That's too hypothetical. But I can say that I think the data has been very well received by clinicians.
Chema, I don't know if there's anything you want to comment on related to, from the commercial perspective.
I think you've answered it perfectly. Thank you, Marci.
Thank you very much. The third question, the last one from me. The market penetration of this drug, what would be the speed of the market penetration that you're assuming? According to your presentation this time, for the education activities, I feel that it will take a little while. Recently you are doing very aggressive marketing activities, and I feel that you are taking the positive reaction. Immediately after the approval, do you think the penetration would take place immediately, or do you assume it will take a relatively longer time for the market penetration?
Chema, would you please answer?
Thank you for the question. I guess I'll start just by saying that we're not gonna disclose FY 2023 sales here. That will be a subject for a later IR call. What I would say is obviously we have mapped this out very carefully and, you know, our investments are tailored to maximize this opportunity and to, you know, get this potential medicine to patients as quickly as possible. You know, probably the best thing I can say is that's probably all I can say for now, but please be patient with us, and very shortly we'll give you further information on that.
Understood. Thank you very much. That's all from me.
Next, Mr. Haruta from Credit Suisse Securities, please. I think it's Sakai. Sorry, Mr. Sakai, please.
This is Sakai from Credit Suisse. Thanks for taking my questions. I have a couple quick questions. The one that I'm interested in duration of the treatment with fezolinetant with this data. Safety data should help, I guess, for the patient awareness. However, in a real setting, real clinical setting, you know, 80% of doctors you said are unaware of the menopause or VMS, which is amazing number, by the way. How is that going to impact the doctors treating patient and patient wish to be on therapy? Can you comment on this first question?
Thank you. Chema, could you take this question?
Yes, thank you. I'll answer some of it, and then I'll pass over to any of my colleagues to answer further. Just to answer the first point, the average or, say, the median duration of treatment is, we estimate 7.4- years for an individual patient. Now, what that means in terms of days of therapy or duration of therapy for forecasting purposes is different. We're forecasting six to 10-month range for forecasting, depending on the year. But as I say, for an individual patient, it's 7.4- years. So I hope that answers that part of your question. The second part of the question is, it's quite a complicated picture to answer, but let me start and then invite either Marci or Lynn to further comment.
The situation with the lack of education, we believe, is because of many different things. One is not being educated at, you know, school, at university during their training, of course, but that's changing. Another thing is obviously a very negative reaction to what happened in with hormone therapy. Once hormone therapy you know the risks associated with hormone therapy were made clear. For a long time, the interaction between the doctor and women has not been an easy one in this area because of a lack of treatment options. We see that changing quite quickly because of well A helping the education gap be served, but also if another treatment option was available that was safe and effective, that interaction between doctor and patient would be dramatically different as well. I don't know.
Perhaps Marcy's thought has commented on this many times in our team meetings, so perhaps I'll start with you, Marcy, to add any further color.
Sure. Thanks, Chema. I'll start by saying that, you know, we've had an extensive number of discussions in not only planning our phase three pivotal program, but during the conduct of phase three with regulators, and that includes EMA, about what our trials needed to demonstrate and what kind of data the agencies would be looking for, not just related to efficacy, but related to safety. The agencies clearly understand the epidemiology of vasomotor symptoms, which Chema just did a wonderful job of summarizing. I think what's important is we're under review right now. We are confident in the data package we've provided. We are confident that we have thoroughly characterized the safety profile of fezolinetant, utilizing the data from our pivotal trials, which we've had dialogue with agencies, as I noted, on their design.
As it relates to label, et cetera, I think we'll see what happens when the agency provides us that feedback. Again, this is an agent or a potential therapy which could really change patients' experience and their quality of life. I think the agencies will take that into consideration based on data. Again, we can't really speculate as it relates to what that might say or the label might say, but certainly we feel that we've demonstrated that there's a very positive benefit risk here for patients.
Thank you. The second quick question relate to the, well, again, duration of the treatment, but price. I know you're not gonna talk about price, but if every patient is gonna stay on the treatment for more than seven years, that patient must be very price conscious. Now, is that going to be one of your consideration when you go to payers? That's my second question.
Thank you. Chema, could you take this question?
Yeah. Thank you again for that question. I guess, you know, I can't really say a lot more than I've already said, and I hope you understand that. Obviously, country by country, the situation is different and the reimbursement systems are different. United States is completely different to other countries in terms of access and the pricing reimbursement system. What I would say is we've carefully analyzed each of these markets in great detail, and we believe we have a very robust plan for each market that again reflects, you know, price and reimbursement and access that reflects the value that this potential treatment could bring patients and society. We've worked through this very diligently and, you know, we're very confident in our plans.
You know, once we get closer to the launch, of course, we can have a different discussion with more details for you.
Thank you very much, and congratulations.
Thank you.
Thank you. Thank you very much. There are some other people who would like to ask questions, but time is up, so we'd like to close this meeting here. Thank you very much for your time today. Including fezolinetant, we will continue to provide information to you. If there is anything unclear, please contact our IR department. Thank you very much for your time today.