Astellas Pharma Inc. (4503) Earnings Call Transcript & Summary

[Interpreted] Thank you very much for joining out of your very busy schedule today. I'm delighted to serve as emcee 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 the language of your preference from the Zoom screen menu. And presentation materials are not posted on our website. If you want to get one, please contact the IR department. Today's presenters are Executive Director, Global Development Project Leader, Dr. Marci English; and Senior Vice President and Head, Medical Specialties, Global Strategic Brand Marketing, Dr. Txema Sanz. The Q&A session will be joined by Dr. Andrew Krivoshik, Divisional 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, and 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 2 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. Then I'll turn it over to Txema 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, and we were excited to present this data at NAMS. There is 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 3 that highlighted pooled efficacy data from the Phase III SKYLIGHT 1 and SKYLIGHT 2 studies. We also had 3 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 milligrams, fezolinetant 30 milligrams or placebo once daily with a randomization schema of 1:1:1 in each arm in women aged 40 to 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 1 dose of medication. As you can see, the participants were equally distributed among the 3 treatment arms. Of the number of women enrolled, 599 met the criteria for the endometrial health set, which required endometrial biopsies to meet the prespecified 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 normal 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 the 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. And 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 of more than 3x the upper limit of normal were observed in 6 participants who received placebo, 8 who received fezolinetant 30 milligrams and 12 who received fezolinetant 45 milligrams. Overall, 8 participants had ALT values more than 5x 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 8x the upper limit of normal ALT, this patient was receiving placebo. AST values more than 5x 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 the 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. And 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 1 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. Malignant endometrial tissue was identified in none of the women receiving [Audio Gap] 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 with 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 1 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 3 measures of patient-reported sleep disturbance as early as week 4 of treatment. Lastly, while examining our data, we also saw fezolinetant demonstrate superiority to placebo across various subgroups. And an important prespecified analysis investigated the efficacy of fezolinetant in black and nonblack 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 nonblack women. And our data indicates that fezolinetant was efficacious at week 4 and was maintained through week 12 in both black and nonblack 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 3 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 of 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 disrupt sleep, which in turn affects daytime productivity. This last study, which was presented in an oral session, aim 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 and midlife. It 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 required 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 working in the industry. It also suggests that women want treatment, and there's an existing unmet need for safe and effective nonhormonal 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, Marci, and thank you, all of you, again, for joining this meeting. So 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. And today, I'll share with you some insights from over 5 years' worth of market research as well as the details from our disease education activities. Now the 3 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; and thirdly, I'll talk more about what Astellas is doing to help educate both health care professionals and women. Next slide, please. So if you look at the global picture, you'll see that there's an estimated 1.2 billion women that will be peri- and postmenopausal by 2030. So no matter where you are in the world, millions of women are suffering from VMS associated with menopause. And we know that VMS are the most common symptoms of menopause for which women seek treatment. They occur in up to 80% of women aged 40 to 64, and they persist for a median of 7.4 years. So 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. And as a result of that, there's been a steady decline in the use of hormones across most of these markets. So 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. So really, what this demonstrates is that many individuals chose not to take hormone therapy or they cannot take hormone therapy. Next slide, please. And again, looking at the United States in a bit more detail here, more than 30 million women between the ages of 40 to 65 are postmenopausal. Now among them, more than 10 million of them by 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. So as I mentioned earlier, the second point we're going to talk about now is the health care professionals and insights that we have from market research and the women's insights. So first of all, looking at health care professionals, we've interviewed more than 6,000 doctors actually and more than 8,000 women experiencing VMS over the last 5 years. So first of all, I'm just going to share with you 3 key insights we learned about doctors in the United States. First of all, the knowledge, doctors' knowledge of the mechanism of VMS is very low. 80% doctors are unaware of how VMS works, particularly the role of the [indiscernible] you're on. 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 satisfied with current -- very satisfied with current treatment options. Even worse, 35% of doctors feel powerless in helping patients because there's -- they perceive there isn't a safe and effective VMS treatment. Doctors want alternatives to hormone therapy. Next slide, please. Now we're going to focus in on the market research insights from women. And as I mentioned to you, we've interviewed over the last 5 years more than 8,000 women across the globe experiencing VMS, and there's 4 insights I'd like to focus on. Firstly, 90% of women indicate their experience with VMS is significantly worse than they expected. So 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 to 64, and they persist for a median of 7.4 years. Thirdly, we know from this research that women are highly, highly motivated, yet misinformed and frustrated by the information they get. So a real -- 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, and the biggest complaint from patients is a perceived lack of treatment options that are both effective and safe. If we go to the next slide, please. So building on these powerful insights, last year in September, so just over a year ago, we successfully launched our first multichannel 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. And we also have 500 employees in Astellas delivering disease education materials, this is all in the United States at the moment, so 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. And to date, we have reached 132,000 doctors and counting. And 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. So of course, there are more educational gaps to fill. For example, doctors do not fully understand that women of color experience VMS at higher-than-average prevalence, as Marci already mentioned. So we're contributing to provide educational materials focused on the epidemiology of VMS included in these subpopulations. And 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. So as we move forward with our efforts, we'll continue to provide you with further updates on these educational programs. And now if we go to the next slide. So I've told you about our education activities in doctors, the previous slide. And now I'm going to 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. So 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. And 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. And 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. So the endemic health care website examples are websites like WebMD and the Mayo Clinic. And we also have some initial data on video completion rate for those on YouTube with other endemic partners, which is already 80%. So 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. So for example, TikTok, this is a platform where the 40 to 49 and the 50-plus 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 in 90% of women aged 40 to 65 by the end of this fiscal year. So we go to the next slide, please. Thank you. So 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. And 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. So 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 Hiro Ikeda, and he can moderate. Thank you.

[Interpreted] 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. [Operator Instructions] This fezolinetant is still before the approval. Therefore, today, when it comes to the sales strategies and price strategies, the answers might not be sufficient, so please do understand that. After the approval, we are planning to have another -- this kind of session. So when it comes to the sales strategies, please wait for a moment for the details. Now please start the question. Thank you for waiting. First question, Nomura Securities, Mr. Kohtani, please.

[Interpreted] Kohtani from Nomura Securities. Can you hear me?

[Interpreted] Yes.

Questions in English. So first of all, congratulations for the wonderful data. So I think there is -- as you may know, there's a big disconnect between what the market thinks about fezolinetant and I think the estimation of the fezolinetant's market potential. So one of the key information we were missing is how quickly the drug works, sort of a wow factor for doctors and patients. And the most effective treatment, I think, hormone treatment for now, I think, takes a few weeks to work. And 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 the -- on how effective this drug works. So 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.

[Interpreted] Thank you very much. Marci is going to talk about from the perspective of science. And the commercial perspective, Txema is going to give you the answer.

Thank you, Hiro. So if I understand your question and statement correctly, yes, fezolinetant, as you saw from the data today, works as soon as 1 day after taking. And 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. And they state that hormonal therapy takes anywhere from 3 to 6 weeks, I believe. So -- but certainly, those guidelines would provide the benchmark for the expectations of hormone therapy. And Txema, I'll let you address from a market...

Yes. Thank you. I think the question also touched upon the uptake and the potential of the product. So I would like to say, 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 to 65. And 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. And the key point is women want an alternative to hormone therapy. And our research also confirmed this because 79% of women state, they would likely talk to their doctor in the future if a novel, nonhormonal treatment option were approved and available. So 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 nonhormonal treatment, these facts give us really -- make us very confident in our uptake assumptions and peak sales share. And 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, Txema. Thank you. I would be glad to. Good morning, everyone. So again, as Txema 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. And the utilization of that treatment option of the past has declined dramatically by 75% in the last 2 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. So this leaves a major gap in treating these symptoms for women. So again, I'll reiterate, from a U.S. perspective, the opportunity, and there's really 4 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 you -- as I just mentioned in the graph here, the utilization of the treatment option of the past, which was HRT, has declined dramatically. And then lastly, we know that these women are highly motivated to seek options, which is critical to our success. So 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. And then 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 nonhormonal treatment option were available. So that's 8 out of 10 of the women that we spoke to said that they would talk to their physician if they learned of a nonhormonal treatment option. So for all of these reasons, we feel very optimistic about the potential of this product in the United States to help women.

Just the second question is, I know -- I'm very aware of Astellas has a 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 paper showed 12% of patients are contraindicated for hormone therapy due to cancer, heart attacks, liver problems, et cetera. Another 45% of women, I think, require caution to use hormone therapy due to smoking and diabetes, family with history of breast cancer, et cetera. So can we assume that the uptake in that 12% that is contraindicated for hormone replacement therapy, there -- that uptake there will be pretty quick? And what I'm struggling to understand is how should we think about the uptake in the remaining 49% who are cautioned -- I guess, require caution to use hormone therapy is the second question.

[Interpreted] Thank you for the question. First, Txema, please.

Thank you so much for this question. And yes, it's -- you're absolutely right. There are different -- well, there's clearly different populations of women that either cannot take hormones or choose not to take hormones. And the paper you're referring to is a review of chart records or patients that already present to doctors. And 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%. So that's composed of contraindicated patients, as you said, about almost 12% patients that have preexisting medical conditions or risks like cardiovascular risk or other such risks, 49%. But overall, women who were first to taking hormones is 57%. So that -- there is a large number of women who want an alternative, who are already presenting to doctors. But we also have to -- so for us, these are all potential women and targets that could benefit from another therapy. But this is not the whole market. So 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 nonhormonal alternative. So that's another big group that is in addition to the groups that I've spoken about already. So I hope that answers your question. Please let me know if there's anything else.

That does perfectly. So third and last question, just the safety data checks up. I think the biggest concern, of course, is effect on endometrial thickness and effect of cancer risk. But I think as you explained, you 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 3 upper limit normal liver enzyme levels as compared to placebo in the fezo 45 milligrams. And I think there was an increase in the fezo 30 milligrams also. Now I understand the high [indiscernible] was not met, and it looks like no bilirubin changes also. So this is basically -- can be interpreted as a temporary rise, not really a significantly -- something that require caution from the FDA. That's my last question.

So Marci, could you take this question?

Yes. So 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, Kohtani-san, for your question. [Interpreted] Next, Mr. Yamaguchi from Citigroup Securities, please.

Can you hear me?

Yes.

So this is Yamaguchi from Citigroup. I have 2 quick questions. The first question, you mentioned about several patient awareness program, including TikTok or SNS. Given in the past that patient awareness program was focused on the so-called TV program called DTC, and we spent millions of millions of dollars in the past, in general, is it fair to say that those way to, how would you say, increase patient awareness has been changed because of those SNS era? And 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 1990s or early 2000? That's the first question.

Thank you, Yamaguchi-san. Txema, could you take this question?

Yes. Thank you very much for the question. And I'm going to hand to Lynn in a minute -- moment, who will give you more information. But just allow me to say a couple of things. So we've started this campaign, these educational campaign using different channels, digital channels, omnichannels and so on, as I've mentioned, and some innovative areas like TikTok. But our plan is to engage with large media, television advertising from October. And that would also be the case come -- when we -- if the product is successfully approved. Because it's very important to have a mixture of channels. And the TV channel has a very big -- the broadest impact on the number of patients, more than any other channel. Because if you remember, we have to target 30 million women in the United States. That's a big audience. But I'd like to ask Lynn. Lynn is the expert here and perhaps can give some more opinion.

Sure, Txema. Yes, thank you very much. I mean, I'll answer this in 2 ways. First, just looking at our reach to date in reaching women. So as Txema mentioned earlier, we just launched our DSA campaign for women specifically in August. So it's new. But we're seeing very strong engagement. After just a month or 2, we've had almost 300,000 visitors to the website. Our video completion rate is 80%, which is -- that means these patients are listening to the videos from start to completion, 80% of them. And this is just 1 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. So we're really excited about that. And as Txema said, we will launch with a variety of channels for direct-to-consumer advertising, a variety of channels. But by and large, TV will be incredibly important because of the 30 million women that we need to reach. And so we will be launching with a direct-to-consumer campaign on television. 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. So this experience that we have in this area will be extremely relevant with fezo because we believe it will be a heavily consumer-driven brand. Thank you.

A quick second question, please. I think you used to have running -- I mean, clinical trials run on the 30 mg and the 45 mg. But my understanding is that you filed only for 45 milligram to the agency at the moment. Given the balance of efficacy and safety, I thought that some patients might want to take at a low dose first then goes to the high dose in the future because of -- they wanted to check the efficacy. But you seem to go to 45-milligram one dose. Is this situation may change your strategy or it's not really?

[Interpreted] Marci?

Yes. Yes, I can answer that question. We -- as you say, we have filed with the 45 milligrams as our dose for potential approval. And in evaluating the efficacy data and the safety data, Astellas feels that this provides the best benefit-risk balance for patients. And again, we look forward to the agency's assessment of the totality of our data.

Thank you for your question, Yamaguchi-san. [Interpreted] Next, Mr. Hashiguchi from Daiwa Securities, please.

[Interpreted] I'm Hashiguchi from Daiwa Securities. 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 and could lead to the continuation of their treatment because of the high efficacy. Please explain.

[Interpreted] Marci, could you please respond to this question?

Sure. Sure. 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. And 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 3 independent measures of sleep. We used the PROMIS SD Short Form, which is the sleep disturbance form. And we also used 2 patient global impression scales: one, a patient global impression of change scale; and another which was a patient goal impression of severity scale. And 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 3 independent PROs, we saw a benefit. Women reported a benefit in their sleep as their VMS declined and as they, of course, took fezolinetant to get those VMS episodes to decline. We also present -- analyzed [indiscernible], for example. And we have some manuscripts in press -- or in preparation, rather, looking at menopause-specific quality of life. We will be hopefully publishing that in the near future. I think to just round out your question about whether or not patients are getting this benefit, I'm going to 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. And I think that, that in and of itself demonstrates that patients are receiving a clear benefit from -- in taking fezolinetant as it relates to quality of life.

[Interpreted] Next, Morgan Stanley MUFG, Mr. Muraoka, please.

[Interpreted] I'm Muraoka from Morgan Stanley. Can you hear me?

[Interpreted] Yes.

[Interpreted] So the marketing of 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 appearing, 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 or the insurance coverage. It is okay if it is still abstract. But is there something that you can share with us?

[Interpreted] Then, Txema, I think that there is a certain restriction for the disclosure of the information. But as much as possible, could you answer this question?

Thank you very much for the question. And 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 health care systems and also to society, obviously. So 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. And 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, Txema. Thank you very much, and thanks for the question. This is very relevant. So we do anticipate that the patients that will go on fezolinetant will predominantly be commercial payers. And 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. So 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 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 can learn. And what we've learned is they want to make this condition a priority. We've had -- we've been having preapproval 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 nonhormonal option for a very high unmet need in their current membership populations.