Thank you very much for taking your time to attend the financial results presentation meeting of Eisai Company Limited. It is now time. We would like to begin the financial results presentation for the first quarter of fiscal 2024. This is held in a hybrid format with attendees in person in this hall and also attendees who are attending virtually. Please find a flashboard and presentation materials for those of you who are attending in person. Those of you who are viewing online, please check these materials from Eisai's website. I would now like to introduce the presenters today: Representative Corporate Officer, COO Keisuke Naito, and CFO Tatsuyuki Yasuno.
Mr. Yasuno, CFO, please start.
[Foreign language]
I will now explain our consolidated financial results for the first quarter of FY 2024. In the first quarter of FY 2024, despite the continued proactive investment in the growth of the LEQEMBI, both revenue and profit increased in the pharmaceutical business, and both revenue and profit were in line with the business plan, and we could make a good start relative to the focus for the fiscal year. First, revenue was JPY 189 billion, down to 96% of the previous year due to the impact of the one-time income recorded in the previous year. Below, you will find that revenue from the pharmaceutical business, which is our organic business, was JPY 186.6 billion, up 3% from a year earlier due to the growth of what we call three Ls, LENVIMA, DAYVIGO, whose generic name is lemborexant, and the LEQEMBI.
Cost of sales was JPY 39.8 billion, accounting for 21% of revenue, down 1.3 percentage points from the previous year due to an improved product mix. As a result, gross profit was JPY 149.3 billion, at 98% of the previous year's level. R&D expenses were JPY 41.7 billion, up 1% over the previous year. SG&A expenses, including shared profit of LENVIMA, JPY 38.4 billion, paid to Merck were JPY 99.5 billion, at 116% of the previous year's level. Other income was JPY 5.4 billion. As a result, operating profit was JPY 13.4 billion, at 52% of the previous year's level, and the profit for the period was JPY 11.5 billion, 55% of the previous year. But as I mentioned earlier, these were in line with the business plan, and we could make a good start for the fiscal year relative to the forecast. Next slide.
This shows the breakdown of revenue migration. As shown at the top left, revenue for the first quarter of FY 2023 was JPY 196.9 billion. In the first quarter of FY 2024, in the pharmaceutical business, LENVIMA was up JPY 12.8 billion, or 18% from a year earlier. DAYVIGO increased JPY 2.7 billion, or up 29% year-over-year. And in addition, the LEQEMBI grew JPY 6.2 billion year-over-year, and by 2.2 times from the last quarter. These three Ls above the growth of the pharmaceutical drove the growth of the pharmaceutical business, offsetting decreasing factors such as the termination of the HUMIRA marketing partnership in Japan in June last year, which is included in the bar above for products other than three Ls, resulting in an increase of JPY 4.8 billion in revenue.
On the other hand, as shown in the blue box at the bottom, due to the impact of one-time income of JPY 12.3 billion from the transfer of all future economic rights by the Elacestrant recording the previous year, revenue from other business decreased by JPY 12.7 billion, resulting in a revenue of JPY 189 billion for the first quarter of 2024, to 96% of the previous year's level. This slide shows the breakdown of operating profit migration. As for operating profit, as shown in the second lowest blue box, a portion of the deposits Eisai previously received at entering into the global strategic collaboration for MORAb-202, JPY 4.8 billion, was recorded. This was from BMS following the end of the collaboration, which was JPY 4.8 billion. This was booked last year. However, as stated in the line below, revenue from one-time payment last year had a major impact.
As a result, it was down by JPY 12.6 billion to JPY 13.4 billion, or a decline of 52% year-on-year. Despite the decline, thanks to the growth of three Ls, we were able to proactively grow investment in the LEQEMBI at the same time as increased segment profit of the pharmaceutical business. Fiscal 2024 consolidated financial forecast, which remains unchanged since May disclosure, we will continue to focus on our efforts on three Ls, including the LEQEMBI, and maintain financial discipline to control cost and expect growth of both revenue and profit without falling into short-termism. From a mid- to long-term perspective, we will continue to proactively spend on the LEQEMBI to sustain the enhancement of corporate value. Now, let me talk about the progress of the LEQEMBI. First, let me talk about the regulatory update and rapid expansion in launched countries. Next, here is the global regulatory update.
I will report on the status. The regulatory—so I will report on the status of applications for maintenance treatment and subcutaneous formulation, which are important life cycle management issues, and the status of submissions in countries and regions. The regulatory processes of IV maintenance treatment and SCAI maintenance treatment are all progressing steadily. In addition to the US, Japan, and China, LEQEMBI has been also approved in South Korea, Hong Kong, and Israel, and we will continue to expand a number of countries where it is approved. We will request a re-examination of the CHMP opinion for approval in Europe. Within 15 days after receipt of a CHMP opinion, the re-examination will be conducted with new rapporteur and new members. I will explain in more details in the next slide.
For the European submission for approval, on July 26, the CHMP adopted a negative opinion on the marketing authorization approval after considering the balance of benefits and risks. Let me express the company's position on this. The protocol and the statistical analytical method for the Phase 3 Clarity AD were determined in advance in consultation with global health authorities, including the EMA, the upper body of CHMP, and the endpoints were determined as such. In this study, the lecanemab achieved all its primary endpoints and all key secondary endpoints, all of which had been consulted on in advance, demonstrating statistically significant results. However, such an opinion was adopted, which I would like to reiterate. For benefits, these efficacies have been sustained up to for a long term of 36 months, as presented at AAIC 2024, Alzheimer's Association International Conference recently held, even further promoting Clarity AD results.
Even further supporting Clarity AD results. On the risk side, data also confirmed that the incidence of ARIA, main ADR, was very low at six months of treatment, and most cases were asymptomatic. The incidence of ARIA in actual clinical setting is consistent with clinical trials and is well managed in accordance with the guidelines set by regulatory authorities. So far, for both risk and benefits, we are confident in Clarity AD results. Therefore, we will seek re-examination of this opinion. In order to provide this treatment to patients with progressive and fatal AD, as soon as possible, we will work closely with the CHMP to seek early approval in Europe. Next slide, please. Here, I would like to present actual global results for the LEQEMBI. The quarterly global revenue was JPY 6.3 billion, increased by 2.2 folds from JPY 2.8 billion in the previous quarter.
This growth was due to that the U.S. and Japan entered in the prescription expansion phase while we started selling in China from the last week of June. It is progressing in line with the business plan toward achieving fiscal year 2024 revenue forecast. Next slide, please. Here, let me show you the situation in the United States. As prescriptions expand, the number of medical institutions ordering the LEQEMBI increased by approximately 40% compared to the previous quarter. The average number of orders per medical institution also increased by approximately 30%, and the sales of vials to medical institutions increased by approximately 1.7 times compared to the previous quarter. Monthly revenue also continued to grow, reaching JPY 2.1 billion for the month of June.
Increasing the number of NAS who provide information on the value of the LEQEMBI as specialists in the neurological field was increased in July, and the commercial structure in the U.S. now has approximately 450 positions, which include Biogen personnel. We are aiming at further expansion. We will leverage the latest data presented at the AAIC, which we released recently and will be discussed in a moment, to feature the potential benefits of patients through early initiation treatment and continued treatment after plaque removal. The incidence of ARIA in actual clinical settings seems to be within the range in the U.S. packaging set. We will aim to increase the value through wealth of data and evidence, which only the LEQEMBI has, and establish a strong position as the drug of first choice. Next, please. In Japan, the number of patients receiving the treatment is rapidly increasing.
Revenue increased fivefold from the previous quarter. Sales in July also grew at an increasing pace. Of the 650 facilities that have completed pathway establishment, approximately 500 have initiated the LEQEMBI administration. About 800 physicians have started prescribing the LEQEMBI so far in fiscal year 2024, all of which show that progress has been steady. In addition, the number of physicians who have administered the LEQEMBI to 10 or more patients has increased to 70, and as shown in the figure, the sales to medical institutions have been steadily increasing. The incidence of ARIA remained within the range indicated in packaging set, and the dropout rate also remained lower than expected. In Eisai's home market in Japan, with the efforts made by the entire company and the passionate commitment of the medical professionals, the LEQEMBI is expanding ahead of the business plan. Next slide, please.
Here, in China, after the LEQEMBI was launched on June 27, it has already been adopted by 148 hospitals in 57 cities across the country. First quarter result was JPY 0.2 billion, and we started contribution to patients mainly in private market. One of the characteristics of this region is that, in addition to PET and CSF, we are introducing a pathway model utilizing new technologies such as BBBM online platform, industry collaboration. On the online platform, managed jointly by Eisai and Jingdong Health, a Chinese company, where approximately 300,000 general consumers and about 1,350 AD specialists are registered. Through this platform, information regarding dementia specialists and infusion centers is provided, and also through reminders of MRI tests for ARIA monitoring, through all of which an ecosystem where it is easier to participate in and continue treatment is being established.
The number of people with AD in FY 2024 is estimated to be 70 million. Contribution to patients has been rapidly increasing in China, which may become the second largest market after the US in the medium to long term. Launch has been started steadily. Next, please. From here, I would like to discuss our efforts to develop the LEQEMBI. We have spent more than 20 years to develop the LEQEMBI, and during 19 months after its launch, from OLE study and various sub studies, we have accumulated robust findings in this area, both in quality and quantity. Based on that experience, we believe that the LEQEMBI's unique value has been demonstrated once again with even more data, namely, early start of treatment and continuation of treatment after plaque removal maximizes efficacy. Secondly, even in long-term treatment, the high level of safety is shown. Thirdly, suggested effect on tau cascade.
I would now like to turn to the latest updates from AAIC, the International Academic Conference held the other day, to describe these unique points. First, these are the results from 36 months of long-term treatment with LEQEMBI obtained from Clarity AD OLE study. The top green line shows the change in CDR-SB in the group treated with lecanemab for 36 months. The bottom pink line is the change in CDR-SB in ADNI cohort set as the placebo arm. OLE study, after the initial 18 months of core study, does not have a placebo arm. Thus, ADNI cohort data is used after 18 months. The two lines representing the difference in CDR-SB continue to separate from month 18 to month 36. This demonstrates the meaningfulness of continued treatment based on clinical symptoms.
In OLE study, even in the late start group that started to receive lecanemab only after the start of OLE, there is a clear difference between the placebo. However, in comparison to the difference in clinical symptoms between early start group and placebo, early start shows effects exceeding that seen in late start group. This data can also be considered to suggest the importance of early start of treatment. Lecanemab is the only drug that includes early MCI population who have small accumulation of tau or low tau group, and also subjects who do not have tau accumulation or no tau group in its studies. This slide shows data suggesting efficacy of long-term treatment in low and low tau groups. In low or low tau group patients, after 36 months of administration, 59%, as shown here, right side or left side, 59% was confirmed to have maintained CDR-SB.
Moreover, on this side, in 51% of the subjects, signs of improvement were confirmed. Looking at other indicators such as ADAS-Cog14 and ADCS-ADL-MCI , similar results showing maintenance or improvement in CDR-SB were obtained. As shown here, in low tau and low tau groups, after 36 months of continuous treatment, consistent maintenance and improvement of clinical effects were confirmed. These are also important data showing efficacy of early start of treatment and continuation of treatment. This data shows the importance of treatment continuation indicated by the plasma biomarkers during the gap period. After the core study, there was a gap period before the OLE. During this period, there is no treatment and clinical symptom indicator. CDR-SB is known to deteriorate, similar to that in placebo group.
left top graph shows that during the two-year period without treatment, plasma biomarker Aβ 42/40 ratio suggested increasing trend of amyloid in the brain, but after the treatment was resumed during OLE, the trend was reversed and trended to decline. Similarly, plasma AD biomarkers such as p-tau181 at right top, GFAP at left bottom, and p-tau217 at right bottom also suggest re-accumulation trend during the gap period, confirming that the AD pathology started to progress once again. As shown here, AD pathophysiology-related plasma biomarkers are re-accumulating consistently when the treatment is stopped, and AD-related pathological process starts to progress again. On the other hand, after the gap period, when the lecanemab treatment is resumed, it has been confirmed that biomarker showed declining trend, suggesting the importance of not stopping but continuing the LEQEMBI treatment. This is data obtained from Clarity AD OLE showing safety in long-term treatment.
As for the incidence of adverse events in Clarity AD OLE, in exposure-adjusted ratio, it was equal to or lower than the core study, and no clear increase in adverse events was observed with long-term administration, so no new safety findings were observed. This indicates that in long-term administration as well, safety of the LEQEMBI is high. I would like to once again touch upon the unique MOA of the LEQEMBI centering around protofibrils. The LEQEMBI removes the plaques and at the same time selectively acts on protofibrils considered to be most neurotoxic and protect the neural cell functions. This has been evaluated before and has been reported before. Furthermore, it is beginning to be understood that the protofibrils can be the trigger of the tau cascade in the downstream, and these lead to suppression of tau pathology.
Tau cascade starts with tau phosphorylation causing neurofibrillary tangles, and the lecanemab administration led to results suppressing the progression of tau pathology observed with tau PET. Tau pathology-specific MTBR-tau243 increase is also delayed, which suggests the suppression of tau pathology, and therefore long-term clinical efficacy may be exerted. And once again, what I would like to reiterate is that protofibril may have clinical effect on tau cascade. The lecanemab unique MOA and deep insights on clinical effects will be presented with more detailed data at the key event CTAD in autumn this year. Lastly, I would like to show the key events scheduled this fiscal year. In the second quarter, data was presented at AAIC. As I have discussed thus far, we believe that we were able to show data that will maximize the value of the LEQEMBI.
In the third quarter, at CTAD, plaque and protofibril contribution to clinical effect and real-world data related to long-term treatment for over five years are expected to be presented. In the fourth quarter, we expect approval of IV maintenance treatment in the U.S., and we would like to further appeal the long-term treatment benefits for the patients. In AHEAD 3-45 study targeting preclinical AD patients, enrollment of 1,400 patients is expected to be completed before the end of this fiscal year. Every quarter in this fiscal year, through these key events, we will continue to create strong momentum to maximize the value of the LEQEMBI. This is my final slide. As I have presented so far, the LEQEMBI is unique in that it has dual-action MOA and has advantage by starting treatment early and by treating over long-term and the advantage of long-term safety.
These characteristics are demonstrated by very robust data. We will continue to demonstrate more evidence that will strengthen these characteristics. Based on these, we are very confident that the LEQEMBI will continue to be the first-line therapy for early AD. During the 20 years of development of the LEQEMBI and 19 months after its launch, we have been collaborating with and building solid relationships based on trust with the patients, their families, academia, healthcare providers in order to open a new door to AD treatment. AD is progressive and, in principle, irreversible disease. As I discussed today, the LEQEMBI treatment can be expected to be more effective with earlier treatment and long-term continuation of treatment according to data. With that in mind, our mission is to deliver the LEQEMBI to the patients as soon as possible, and we will do our utmost towards that end.
I ask you for your continuous support. With that, I would like to conclude my presentation.
Thank you. Now, we would like to open the floor for Q&A. First, we would like to hear questions from investors and analysts, and then we would like to ask for questions from media. If you wish to ask questions, please mention your affiliation and name before asking your questions. Now, if anybody among analysts and investors, if you have any questions, please raise your hand. The person in the fourth row, please.
Thank you very much. My name is Wakao from J.P. Morgan. I would like to ask about the LEQEMBI progress during the first quarter. You mentioned that the growth has been made in a steady manner, but the most important thing is for you to achieve this fiscal year's target. Let me ask you a question.
Regarding looking at the progress made during the first quarter, my impression is that in Japan and China, it is steadily growing, but in China, starting from quarter two, the sales started to be posted, which was quite surprising to me. Americas, although it is still growing, but not as in line with our expectation, particularly the current status in the US. Is it really progressing in line with the business plan of the company? If it is the case, at some point in the future, shifting from the linear growth, or there needs to be further accelerated growth. When do you expect such a change or inflection point is going to be made? If you are seeing earlier timing, please let us know.
For the fiscal year, global results progress will be explained by Mr. Naito. Regarding the current status in the U.S., Haruna-san is going to explain.
Thank you for your question. As I said in the presentation, from the global perspective, we believe that the LEQEMBI sales are steadily growing, and progress has been good. Also, the growth rate is also being accelerated. That is how we take. That is also represented in the reimbursement status, and we believe that this upward trend will continue. I would like to ask Haruna-san to supplement my response.
Thank you very much. I am in charge of the LEQEMBI in the United States. My name is Haruna.
Regarding your question about the status of the business during the first quarter, in the United States as well, the progress has been steadily made in line with the plan, and also the width of the prescription, and also depth of the prescription are to be expanded, which are very important for progressing the LEQEMBI. First, regarding the width of the prescription, the prescribers and the number of medical institutions where the LEQEMBI is prescribed is expanding, and which has been steadily growing over the planned. And particularly, about 40% of the new prescriptions were recorded during the first quarter. Therefore, the recent start of the prescription is expanding. And directly appealing to the patients and families in order to encourage them to seek the medical consultation, DTC, or you still can be , is conducted in order to expand the number of patients who will seek medical consultation.
Therefore, we are starting to see the effects of digital marketing. Also, the number of medical institutions with over 50 prescriptions has increased by three times from the previous quarter, and about out of which 70% of the medical institutions have become the larger center for a large number of prescriptions. For this, as Mr. Naito explained earlier, as the specialist in the neurology area, NAS, who is providing information on the LEQEMBI, and also for the neurologists at the medical institutions, we are increasing activities, and we are trying to establish more than 100 medical institutions as large prescribing institutions. Regarding the achievement of the target for this fiscal year, we are planning to see the big waves for each quarter.
During the second quarter, as we have explained today, the AAIC, 36 months, showing the long-term continued treatment as well as the early start of the initiation have shown the benefits for the LEQEMBI that was presented at the AAIC. Also, particularly from the long-term perspective, we needed to consider the treatment for the patient. We have got that feedback from the AAIC. During the third quarter, the new biomarker dual-acting MOA, how it is important, will be presented during the third quarter. For the fourth quarter, the biweekly administration will be reduced in terms of frequency to monthly administration, which will increase the convenience of the patients. There will be the new indication for the SC will be approved during the fourth quarter. Therefore, it will enhance the convenience of the patients.
We are establishing the pathway, and also we are closely working with the healthcare providers and the CMS and the infusion center and the payer and advocacy groups. There are many stakeholders with whom we are discussing and consulting, and we believe that we have been able to establish a very strong relationship with them. So based upon such latest data and experience and expansion of the indication, utilizing such great advantages, we are going to accelerate the expansion of the width and the depth of the prescription going forward. Thank you very much. On a monthly basis, as you have been showing us now, on a monthly basis, this linear expansion of growth will be made into an exponentially accelerating growth trajectory. We have an expectation for that. The second question is about the status in Europe. These 36 months are going to be submitted.
Including this 36-month administration data, this CHMP's negative opinion that has been given, do you think that sufficient data do you hold in order to reverse this negative opinion of CHMP? With this question, I would like to call Dr. Lynn Kramer to respond.
Yes. Thank you very much. Let me discuss this CHMP recommendation. On July 26, the EMA announced that it has recommended the refusal of marketing authorization for LEQEMBI after considering the balance of benefits and risks, as Keisuke Naito mentioned. As I understand, the ground for this refusal, however, is primarily safety. However, we would like to emphasize the incidence of ARIA in actual clinical settings is not higher than in the clinical trials and is being well managed in accordance with the guidelines set by each regulatory agency where it is commercialized.
The protocol for the Clarity AD phase 3 study was determined in advance with health authorities, as was mentioned. The results in the trial were evaluated using evaluation criteria and analytic methods that were determined in advance. In this trial, LEQEMBI achieved its primary and all secondary endpoints, demonstrated highly statistically significant results. Despite this, of course, we are disappointed that CHMP adopted a negative opinion. The efficacy of LEQEMBI has been sustained up to 36 months, and the long-term safety has also been established, as shown in results at the AAIC in 2024. In order to provide this treatment to European patients as soon as possible for the treatment of this progressive and fatal disease, we will seek re-examination of this opinion and will work closely with the CHMP to seek early approval.
LEQEMBI has been approved in six countries and several others we hope shortly will approve, and it has been proven that the benefits of LEQEMBI outweigh the risk in each of these countries. We firmly believe that as the best equipped and single treatment for this progressive and fatal disease, it will be made available to patients in the EU without delay. AD communities, such as patient organizations, are spontaneously writing letters to EMA, many, many letters. These activities include AD experts, patients, and key opinion leaders from various parts of Europe, many parts. The European Commission regulations allow an applicant to request a re-examination of a CHMP opinion. Re-examination will be requested within 15 days after receipt of the official CHMP opinion in writing. The company will then submit the detailed grounds for requesting a re-examination within 60 days after receipt of this opinion.
New rapporteurs will be appointed for the re-examination, and then EMA will have 60 days to review Eisai's re-examination documentation. We understand that the results of this re-examination will be issued within this calendar year. In order to provide this treatment to patients in the EU without leaving anyone behind for the treatment of the progressive and fatal AD, we remain confident in our robust data, and we will work closely with the CHMP to receive early approval. Thank you.
Thank you very much. APOE homozygote, would you please give us any comments on that?
[Foreign language]
We're unable to comment specifically on the regulatory aspects around APOE homozygotes. However, we will work closely with the EMA with the goal of trying to provide access to LEQEMBI for as many patients as possible. That's a question that we would have to discuss further with EMA.
[Foreign language]
Thank you very much. Understood very well.
[Foreign language]
Would there be any other questions? Yes. Audience members seated in the third row, please.
I'm Hashiguchi from Daiwa Securities. I have two questions. First is about LEQEMBI, current status of LEQEMBI. According to your presentation about Japan, dropout was lower than expected. That was mentioned during the presentation. Are you mentioning dropout only due to ARIA or dropout due to all reasons? And specifically, what was the expected level of dropout, and what is the current level of dropout? I believe that after the start of the actual treatment, it has not been much time has not elapsed yet, but that is the question. And this was on Japan, but if you have similar information regarding the US, could you share that information?
Yusa-san will respond, and then regarding the US, Haruna-san will respond.
Mr. Hashiguchi, thank you for your question. I am responsible for LEQEMBI commercial. I'm Yusa. I will respond. First, regarding dropout and the specifics of the patients who dropped out, it is not limited to the reason of ARIA for dropout. All side effects and all circumstances are taken into view, and dropout ratio was much lower than the percentage that we initially expected. But as you have rightly mentioned, it has been only quite recent that administration in actual clinical setting has started. But in the first six months, according to various drug data, there is a dropout ratio data for the initial six months. And in comparison to these data, dropout ratio can be said to be lower. About the US situation, Haruna-san will respond.
This is Haruna responsible for the United States.
As Yusa-san reported about the situation in Japan, similarly in the United States, including ARIA for all side effects, adverse events. So far, the incidence is about less than half of the incidence in Clarity AD and similar to what is described on the package insert. In AAIC, some real-world data were presented. If I may cite one example, Columbia University had 120 patients, and based on the experience of administering LEQEMBI to 120 patients, a report was presented. According to this presentation, ARIA incidence and continuation of administration in these perspectives, benefits exceeding clinical studies were achieved. Therefore, we believe that progress has been smooth in terms of long-term treatment. Low incidence of adverse events. What is your analysis of the reasons as to why adverse events incidence is lower?
Is it because of different patient background between clinical studies and real-world, or is it because of a difference in monitoring of AEs during the clinical trials and the real world?
That question will be addressed by Owa-san. Thank you, Mr. Hashiguchi, for your question. This is Owa speaking. I am Chief Scientific Officer. Generally speaking, what the cause is cannot be concluded without a detailed analysis. The point raised by Hashiguchi-san may be a possibility, but which is more important, we will have to observe more over longer term of administration after real-world data is accumulated more. To specify cause, potential cause will be premature, but we recognize the point raised by Hashiguchi-san is an important point. Second question about development strategy of MORAb-202 going forward.
As I announced, Eisai will continue to develop MORAb-202, but it will be developing on its own. Is there any change to development strategy? Will Eisai be exploring a new partner?
Once again, Owa-san will address that question as well.
Hashiguchi-san, thank you very much for that question. This is Owa speaking. First, with BMS, we had a very close discussion, and because of the differences in strategies of development portfolio, this partnership was ended. But we believe that there is a solid value in MORAb-202, and therefore we will continue to develop. And in doing so, what becomes important is efficacy. In the past academic presentations and papers, I think you can see that there is efficacy. The issue is in long-term treatment, can we maintain QOL of patient? And is there going to be how can we control ILD?
That will be a key issue. Clinicaltrials.gov has certain information from which you are able to understand that we have four different schedules or administration regimens: intermittent administration or steroid co-administration. These are being explored, and we have accumulation of data recently. Based on these data, we are holding advisory board to consider what schedule we should follow in further development, and details are being worked out right now. In the near future, through academic presentations, we hope to present how we plan to continue development under what administration regimen. Gynecological cancer, I think, will continue to be the focus for this cancer since folic acid will be highly present. Clinicians' opinions will also be taken into consideration to determine our development strategy. I believe in the near term, we will be able to discuss that in more detail. Is there any possibility of partnering?
I forgot to respond to that question. I apologize. We have not rejected a possibility of partnership. We would like to continue to look at the additional data, and I would also like to pursue those possibilities as well.
So the person who has raised hand through online, excuse me, rather the person in the second row, Haruta of UBS Securities,
as regards to lecanemab, I have a question. Lilly's Kisunla is going to be launched both in the U.S. and in Japan. And after approval, what kind of response have you heard from physicians and also frequency of dosing and efficacy and safety? And after a certain period, the donanemab dosing will be stopped. And what has been the response from the medical world?
I believe that your accounts may have given you the positive response to you, but have you ever had any response you have heard?
For your question, Naito-san is going to respond. Let me share with you some assumptions. We believe that the disease of amyloid AD or Alzheimer's disease is a progressive which will continue progressing even after plaque is removed. That is how we interpret it. So after turning the plaque into negative, and then the dosing may be considered for stopping. The criteria and also the conditions of patients are not shown by data yet for Kenya. After participation in the AAIC, an atmosphere and also how we felt at the venue can be shared with you by Haruna-san. Could you please report on how you felt at the conference?
The response you felt from physicians at AAIC in the United States, that will be shared with you by Haruna-san.
Thank you. I am in charge of LEQEMBI in the United States. My name is Haruna. Regarding the response at AAIC, the 36 long-term data was presented at the congress for which many physicians recognized the importance of long-term continued treatment and also for Alzheimer's disease. Continued treatment is very important. That was the feedback from physicians. The difference between the drugs are now compared and considered. What is most important, in our opinion, is we have obtained a lot of knowledge. Since the accelerated approval, we have heard from many physicians and healthcare providers, and we collaborated with them to establish pathways. When it comes to this pathway, other companies are not able to use our pathway.
Therefore, they need to start establishing pathways on themselves from scratch. As far as we have heard from physicians, LEQEMBI will continue to be the drug of first choice. The value of a long-term continued treatment and the significance of continued treatment are differentiating us conspicuously from the other.
Thank you for your question. I understood very well. Thank you very much. My second question is the subcutaneous maintenance treatment in the United States. I think at the previous briefing session, by October or around October, the submission will be completed. And if earliest, and then the approval may come around in June next year. So let me confirm whether that is the case now. New indication for IV and a new patient are going to be increased.
When the SC maintenance is allowed, and then how much of such existing or IV patients are going to be shifted to the SC administration? How big the need is? Dr. Lynn Kramer is going to respond to your question.
Yes, thank you. As you know, we have already submitted the IV maintenance, and we expect approval in this fiscal year. We also submitted the subcutaneous dosing regimen for initiation of therapy in a rolling submission previously. We expect to complete that, just as we said before, by the end of October. And then we expect approval in June or sooner, depending on whether we have priority review or not. And that will be FDA's decision when we submit our final documentation in October. Does that answer your question?
Yes, for when the SC maintenance treatment is approved and among the existing patients, how big the needs for that SC maintenance treatment do you see? So regarding the needs of shifting from the existing IV to SC maintenance dosing, Haruna-san, who is in charge of the US, is going to respond to that question. Thank you for your question. My name is Haruna. I am in charge of LEQEMBI in the United States. First, the needs for SC, I would say that there has been a great expectation at the AAIC conference. There were lots of questions and a lot of expectations in the Q&A session at the congress meeting. When is it going to be approved and how you are completing the submission and so forth? Many questions were asked. And IV therapy and SC therapy will both become available in the future.
In accordance with the lifestyle of patients, patients will be able to get more flexibility. So for SC administration, they may be able to administer at home, and that will give a great benefit for patients. Thank you for your question. Thank you very much. Next, attendee who is participating online, Yamaguchi-san from Citigroup, please. Please unmute. This is Yamaguchi from Citigroup. Can you hear me? Yes, we can. Thank you. I have one question. This is to clarify what Dr. Lynn Kramer was explaining earlier, which is about LEQEMBI in Europe. Within 15 days, response will be submitted. And I may have missed this. Within 60 days, review will be carried out. 60 days, meaning that in two months' time, review will be carried out. So the timing is very clear. Am I mistaken? Could you clarify that once again? Lynn Kramer will respond.
Yes, thank you. It actually is a 4-month period. After we receive the formal letter, we have to respond in 15 days that we would like re-examination, a formal response. We will then receive the list of questions that the CHMP and EMA have. We then have 45 days to respond to those questions. And then there is a 60-day period for EMA to identify new rapporteurs and for preparation and review of those materials. And then there will be a new oral explanation at that point. So it's 4 months from now, approximately. Is that clear?
[Foreign language]
New rapporteur, meaning new reviewer?
Yes, actually two. So in a re-examination, EMA needs to appoint new reviewers. And there are two, one from one country and one from another country.
[Foreign language]
Thank you, that is all.
Muraoka-san from Morgan Stanley, please unmute yourself.
Thank you very much. I am Muraoka, Morgan Stanley.
For SC maintenance, schedule is clear to me, but SC induction, or I mean initial treatment, SC induction therapy, could you please share with us current status? Perhaps you are doing the dose optimization as regards to dose 360 for maintenance and so doubled 720 milligrams. Maybe not because of the optimization. So what is going to be the timeline and to which direction you are heading for and where the current status is? Could you please respond? Dr. Lynn Kramer is going to respond.
Yes. We have already started the submission of the initiation dose with FDA. We have received agreement on a rolling submission, and we have submitted the CMC, the manufacturing component, and the safety component. We were asked to do a three-month trial, and that has already been initiated and will complete in the second quarter.
And then we will be writing the dossier, the clinical dossier, and submitting it in October. And then the FDA will review that initiation dose dossier. Lynn, could you comment on the induction initiation treatment? That's what I'm talking about, the induction treatment. What I just described is the induction treatment. Is that clear? Lynn, you just explained about the maintenance, SC maintenance. No, no. I just described the induction treatment. There's the IV maintenance that's already been submitted, and the IV of the subcutaneous induction treatment is what I'm just describing. Think of it this way: you have to have approval of an induction before you can have an approval of a maintenance. So we are submitting a dossier that includes the induction, and after receiving approval of the IV maintenance, then we can have the subcutaneous maintenance approved. Is that clear?
So IV maintenance, first we had IV induction, then we have submitted IV maintenance, and we are submitting subcutaneous initiation of treatment and subcutaneous maintenance.
Can you check the slide 7? IV maintenance is now under evaluation, and SC autoinjective maintenance therapy is now starting the rolling submission, right?
No. The initiation dose is the new IV maintenance is a component of the induction dose. So those two things go together. You have to have an initiation dose, and then you have the maintenance dose, just like the IV. Muraoka
[Foreign language]
This is Muraoka speaking. I was listening to the translation, so I was not able to follow at all. For this particular issue, could you please once again disclose the information, or if you could add a supplementary explanation to the disclosure material? I am also confused, therefore that will be helpful. Mr.
Muraoka, you were asking about SC initiation induction therapy. So Dr. Owa is going to supplement. Excuse us. Perhaps the intention of your question may have been misunderstood. Could you please once again ask your question because we don't want to have any misunderstanding? SC induction. Rolling BLA for SC maintenance is understood, but for induction for SC, the initial induction treatment, the timeline, the development status, and what is going to be the dose for that, that is something that I was not understanding. Maybe my question was not a relevant question.
Sorry, that question is exactly the question I answered. We are already submitting and have submitted the initial portions of the dossier for subcutaneous initiation of treatment. That's induction. So that is already being evaluated by the FDA. We reported that before.
So the maintenance is also part of that, but you have to have the induction dose approved before you can have a maintenance dose agreed on.
[Foreign language]
Have you understood, Mr. Muraoka-san? I mean, in the maintenance submission and when getting approval for the maintenance, an induction dose needs to be discussed with regulators, so we have to proceed with both. That was the response from Dr. Lynn Kramer. Understood. So I see. Then at around June next year, SC maintenance, if you get approval for that, almost at the same timing, SC initial induction to maintenance therapy approval or agreement will be obtained. So can I understand in that way? Yes, that will be depending on the result of the regulatory consultation.
But starting from IV induction and the SC maintenance, but it will depend on the discussion with the regulators, and the maintenance SC and rolling submission is being made, and then SC induction at the same time, data will be shown, and then if FDA is convinced, and then at the same time, we may be able to get approval for both, but it will really depend on the negotiation with the regulators. If you could understand that, that will be appreciated. Understood. Sorry, I have confused the discussion. Thank you very much.
[Foreign language]
Thank you. Next, we would like to entertain questions from the members of the media. If you have questions, please raise your hand. Yes, the audience member seated on the third row. I'm Susumu Shimoyama, non-fiction writer.
EMA letter, looking at the letter from EMA, almost all cases of ARIA in the main studies were not serious and did not involve symptoms. Some patients had serious events, including large bleeds in the brain, which required hospitalization. That is what the letter says. In New England Journal of Medicine, Clarity AD study adverse events table was published in table 3, looking at table 3, large bleeds requiring hospitalization. Which AE does this fall under? Is this ARIA-H macrohemorrhage? There were 5.6%. There were 5% or 0.6%. And is this what EMA points out as large bleeds requiring hospitalization? That is my first question. And I have another question. Owa-san will respond.
I may have missed the important part of your question since I'm somewhat under the weather today.
So in a nutshell, according to this EMA letter, it says ARIA is not serious, but large bleeds, cerebral large bleeds requiring hospitalizations occurred. That sentence is also included in the EMA letter. And what is this in terms of AE in Clarity AD? And according to a paper published in New England Journal of Medicine about Clarity AD study, there is table 3, and there is a list of AEs in ARIA-H, amongst ARIA-H, macrohemorrhage, I think, is an AE that involves large bleeds. And there were 5 subjects. And I am speculating that this cerebral macrohemorrhage is what EMA is pointing out as large bleeds requiring hospitalization. A macrohemorrhage. So there are microhemorrhage and siderosis. Siderosis is deposition of iron due to bleeding, and that is detected by MRI, a microhemorrhage and/or siderosis.
Five subjects were detected to have these, according to New England Journal of Medicine. Does this require a serious toxicity requiring hospitalization? The number of patients who had this was very small, at 5 patients. There was also 1 similar patient having similar AE in control group. These are symptomatic, but is this a serious bleeding requiring hospitalization? I do not think so. Did you say microhemorrhage or macrohemorrhage? Macro is small. Micro adverse events, microhemorrhage. There were 126 patients who had microhemorrhage. This was 14%. There were 5 subjects who had macrohemorrhage. Macro, since it says macro, I took it to mean that it was large bleed. Cerebral hemorrhage. Maybe my interpretation may have been wrong. Owa-san, we'll supplement. I'm Owa responsible for clinical development in Japan and Asia. So macrohemorrhage, this is cerebral hemorrhage. Microhemorrhage is small hemorrhage.
The response is, as Owa-san responded, these are cerebral hemorrhages. There may be cases similar to a case requiring hospitalization, but these five macrohemorrhages, are they all equal to the large bleeds requiring hospitalization, as pointed out by EMA? That is not clear. Second question, I believe that Eisai will be responding, requesting re-examination within 15 days. And in doing so, AAIC 36 months data, will that be submitted to be reviewed by CHMP, or is re-examination going to be solely based on Clarity AD? Lynn Kramer will respond.
Yes, thank you. Let me clarify one thing you said before. The macrohemorrhage is the same thing as an intracerebral hemorrhage greater than one centimeter. Those two things are identical. And that's what appears in the label currently. We will be submitting no new data in the re-evaluation unless requested by the EMA.
So Clarity AD and our phase 2 study are the majority of information unless EMA asks for something additional. The reason for that is that would restart and require a new submission if we sent additional information from long-term, for example. However, they may request it, and then we would send it in. Is that clear?
Yes, thank you very much. [Foreign language]
I have a third question. When I read EMA letter and about three months ago, Reuters reported that amongst the physicians, there is a nihilism, pervasive nihilism, which is the biggest problem. And this was a quote of Lisa Sperling, not data, but there is a rejection by physicians, and they are not administering. And I believe some mass media in Japan also reported in a similar way. It would appear to me that it would be difficult to change this no matter how much data is demonstrated.
This does not change. I'm wondering why it may be a difficult issue to address. What are your views? How do you understand this situation? Well, amongst the physicians and within journalism, there is a nihilism. How do you plan to address this? Since I think that this is a serious question, Lynn Kramer will respond. Sumimasen. Correction, apologies. Naito-san will respond. Thank you very much. About nihilism regarding treatment, I do understand that there were some nihilism. However, at AAIC, there was a very intense discussion. There were intense discussions. And we launched LEQEMBI, which is a new product. And when we launch a new product, I think this is the type of wall that we have to overcome. Prescribing physicians and patients positively talked about the significance of this drug on many occasions.
Looking at the market reaction, I'm sure that such nihilism will be disappearing.
[Foreign language]
Any other questions? The person in the fourth row, please have the floor. Ai Azuma of The Yomiuri Shimbun, thank you for this opportunity. I would like to confirm with you the current status in Japan. Well, the number of patients who are on this treatment cannot be shared with us because this is based on the guess. But during the Q3 for fiscal year 2023, when you had a financial briefing, 3,500 people by the fourth quarter and also the 7,000 will be the target for this fiscal year. So are you in line with this target or exceeding this guidance? Could you please share with the current status? The sales of vials have been shown this time, but what has been the volume of shipment so far? Could you please share with us?
Yusa-san is going to respond to your question. Thank you for your question. I am in charge of LEQEMBI commercial side in Japan. I think you were talking about a number of patients, but regarding the specific number of patients who are on treatment, we are not able to give you the number. But I can say that we are in line with the target, or rather, we are ahead of the target.
[Foreign language]
are there additional questions?
[Foreign language]
We have run out of time. Unfortunately, we would like to conclude today's earnings results presentation session. If you have further questions, please contact investor relations. Thank you very much once again for taking your time.