Now it is time
To start meeting Eisai Company Limited Conference Call. Today, we would like to talk about the AXA data approval of aducanumab given by U. S. FDA. Now without further ado, I would like to invite Mr.
Naito, our CEO, to start. Thank you. This is Naito speaking. This time around, IDHELM has been granted approval from U. S.
FDA. And upon that approval, the first thing that came to my mind was the FDA's approval of ARICEPT on November 25, 1996. From the date of ARICEPT approval to June 7, 2021. Approximately 25 years have passed and Words cannot describe how we are deeply moved through this challenging journey to finally have the 1st in class drug that can target an underlying pathology of Alzheimer's disease. A review of the describing information for Aricept, a symptomatic treatment for Alzheimer's disease.
And that of Aduhelm clearly shows the evolutions in disease concept, diagnosis and treatment over the past 25 years. At the time of Aricept's approval, there was no effective treatment for Alzheimer's disease. And the majority of cases in Japan were thought to be caused by aging or cerebrovascular factors. Today, it is recognized as a neurodegenerative disease that is caused by The abnormal accumulation of proteins such as amyloid beta plaques and tau and progresses over a span of at least 10 years. Biomarker Research has made great advancement in clarifying the pathophysiology of Alzheimer's disease and has become an overwhelmingly powerful tool for understanding the condition and stage of the disease, understanding and confirming the effects treatment and improving the accuracy of diagnosis.
The prescribing information of ARISF G1996 at the time of approval describes the results of the ADAS GOG and CBIC plus study outcomes, but there was no information about biomarkers outcomes there. In fact, biomarkers were not measured in the clinical trials of Aricept and the methods to measure them have not been well established. In contrast, The prescribing information for Aduhelm includes biomarker information for amyloid beta plaque CSF P tau, CSF T tau
and
evaluates clinical endpoints for CDR SB, MMSE, ADAS COG13, ADCS ADL MCI and NPI10 as primary, secondary and tertiary endpoints in a multilayered manner. With regard to the pathophysiology of Alzheimer's disease, which begins with the accumulation of amyloid beta protein in the brain, followed by involvement of tau pathology and subsequent neurodegeneration, Adulhelm showed the reduction of the amyloid pathology. In its prescribing information, comprehensive evaluation of both cognitive and functional aspects like CDRS B and relating endpoints such as cognitive function, quality of life and BPSD or NPI-ten relating were described. I believe that difference between the two prescribing information is a true indication of the innovative evolution of biomarker research and clinical science over the past quarter century. On the other hand, diagnostic advances have been also been extremely remarkable.
Accuracy of MRI has dramatically improved and the innovations in AD diagnosis and change assessment brought about by probe research in molecular imaging such as PET are prominent. In addition, it can be said that CSF testing now provides the most multifaceted information covering almost all stages of pathophysiology of the AD disease continuum including amyloid beta, amyloid beta 42:forty ratio, tau for tau, p tau-one hundred and eighty one-two seventeen and neurodegeneration, NfL or neuro filament light or tau neurogranning indicators. In particular, there are high Expectations for the implementation of blood biomarkers. Japan and the U. S.
Have made progress in the regulatory aspects of amyloid beta related and tau related biomarkers. Furthermore, various genome related information such as APOE related information is now rapidly emerging and we believe that this will create a polygenic score. With these developments, the formation of a brain health panel, which will enable confirmation of the risk of onset of the disease treatment strategies treatment effects will form a core concept for innovation in the diagnosis, treatment and prediction of Alzheimer's disease in the future. So what is value of Alzheimer's disease treatment targeting underlying pathology in general. For a quarter over a century, Eisai has been working closely with Alzheimer's patients with Alzheimer's disease and their family to understand their needs and anxieties.
Through this socialization, We have come to understand the magnitude of impact for not only patients but also their families. When we think of price or pricing policy as an expression of value, We believe that it should be evaluated based on the multifaceted value of the drug That is so called value based pricing. So values, benefits and various costs of patients and their families are taken into consideration. The cost related to Alzheimer's disease is characterized by the fact that The burden of nursing care and family care is greater than that of medical care itself. This includes decreases in employment and job opportunities for family members due to caregiving.
Burden of care also includes the cost of staying in long term care facilities. I believe that the overall picture of the value can be found by comprehensive evaluation of these factors.
And this value based pricing would be a very separate issue from the delivery of this drug to the patients who are eligible for the treatment. That is to say, how we can ensure the drug access for the patients. These are 2 separate issues. So building the price that will reflect the value of the product would really mean that It is the value of the product that is most innovative to be Reflected into the price of the drug and also this is the essential as the concrete indicator of the innovation, whereas the policy to ensure the of the product that has certain price, this kind of access policy will need to reflect the different systems of different countries as well as the insurance programs available. And we need to put in place various support programs and support mechanism.
And especially, We need to be able to provide this medical services to those who are relatively underserved in the social system, such as low income populations. And we need to focus on the very comprehensive initiative. So through the pricing policies, we initiative. So through the pricing policies, we need to represent the true value of the medicines. And through the access policies, we need to be able to deliver a product to the patients who are in need of this.
And these 2 policies would not be contradicting with each other, and it is very important to achieve those goals. And again, It is probably not too much of an exaggeration to say that it will be the over urging mission of the modern pharmaceutical industry to achieve both of these goals. As for the access policy of Aduhelm, We have to pay close attentions to the copay situations of various insurance programs in the United States. And again, the underserved communities for them, we have to really think about the various measures to overcome healthcare divide in those communities. And we want to collaborate with the VHAs or the other retail pharmacies or NAFC.
And based upon the value based contract, We would like to really offer the various programs to lessen this burden for the patients through the healthcare provider's contract. And also we will be carrying out the free CSF diagnostic testing with the providers, and we will keep the price for the initial 4 years. And depending upon the progress of review, And we will be looking into the access policy in Asian region on a timely basis. And there, in our collaboration with the insurance for the middle income populations, we will be creating the new insurance programs or in collaboration with the financial Institutions, we will try to find a way to try to reduce the burden for the patients or we would like to devise the reinsurance scheme with the insurance. And also for low income populations want to consider the tiered pricing or the collaboration with the NGOs to provide the medicines.
And through the mutual system, We would like to consider various innovative models. And currently, as the ecosystem platform, We are building the EU Eisai universal platform and we would like to further accelerate first in this regard. And so At the Alzheimer's disease modifying the treatment and medicines, they are certainly the core of the solution package of EF. And also, our goal of IAP is to free the people of the worries and anxieties. They would like to lead full life even though they may be suffering from dementia or they would not want to cause any troubles to their family members We would not want to see the further aggravation of their conditions.
And based upon the various science and clinical evidence, would be possible for us to offer many different kinds of the solutions. And also going forward, we will be able to obtain the patient's biomarker data And that should enable us to indicate a better guidance and advice to the health care providers and also through the provision of various services and benefits through this disease awareness and diagnosis and treatment care, we believe that we should be able to make a step forward for the resolution of chassis that we face to date. And last but not least, we are also currently working on the development of anti protofibril Lake Tanabeau for the new anti MTBR tau antibody E2814 for new synapse restaurant E2511. In all of these development, we are currently working on the disease modifying key candidates that will work on the different parts of the pathophysiology of Alzheimer's disease. And based upon that, the patients' biomarker data by properly using these drugs, we think that we can come closer to the fundamental treatment of Alzheimer's disease.
And going forward, We would like to continue with our utmost efforts so that we can continue to contribute to the patients and their family members
the pricing and access. Shimizu is the Group Officer of AD Franchise Special Mission. Mr. Shimizu, can you hear us? Please hold on a minute.
The voice doesn't come
through.
Mr. Shimizu? Shimizu, can you unmute your microphone? Can you hear me? Yes.
Can you hear me? Yes. Can you hear me? Yes, we can clear and out. Thank you.
Thank you for the trouble. Thank you very much for waiting. My name is Shimizu. I'm in charge of AD franchise. I'm now going to talk about pricing.
For price, which is going to be value based pricing, the multifaceted values have been considered Based upon the clinical data from the clinical studies for patients and their families and the caregivers in order to increase the value and benefits and in order to reduce the costs related to various aspects of the disease. And considering all these, pricing is to come. And working on the pathology of Alzheimer disease, and we believe that pricing should be and reasonable considering this is the 1st in class such benefits bringing about such benefits. And in the U. S, As you know, every year, the price is being increased.
But for Aduhelm, we are going to keep the price of Aduhelm for 4 years unchanged. And in order while reflecting the multifaceted values of the drug into the price And when it comes to the expanding access by patients to Aduhelm, co payment or out of pocket payment in the U. S. Is considered. And we are going to introduce various programs.
Access Support Program in the U. S. Is now going to be explained. For most of the patients with Alzheimer's disease are 65 years old or over. And according to our calculation, The target about 85% or over percent of the patients are covered by Medicare insurance.
And most of the Medicare insured people have the additional rider insurance policy. Therefore, regarding There is already a cap on the total out of pocket payment. Therefore, out of pocket payment by patients for Aduhelm should not be significant. And Medicare, if they are disabled and if they have any financial and then draw Edible Medicaid insurance coverage, combination of Medicaid and Medicare. Therefore, there will be no out of pocket payment for such patients and their families.
Even under such insurance coverage, there are no rider policy purchased by those patients. For such patients, On the individual cases, we are going to provide consultation services for insurance coverage on an individual basis. And among them, because of the economic difficulties, if they are not able to pay or afford the drugs, there will be free of charge provision of the drugs if conditions are met. And for those underserved community, in order to improve the health equity and Veterans Affairs, VHA and so forth, as has been mentioned in release. We are now final is the contact agreement.
And with CVS Health, we are now trying to bring into the community in order to have the cognitive screening and NAFC, National Association of Free and Charitable Clinics with whom we are collaborating, about 1400 clinics who are the members of NAFC for providing the cognitive screening and also care to be provided to patients. We are building such a nationwide program. When it comes to private sector insurance, The largest player, Cigna, a value based contract is being now finalized. Based upon the value for patient, cost shall be borne. As we are considering such scheme.
Private sector insurer is covering the insurance for patients and for whom. In order to reduce the co or out of pocket payment for the patients, the co pay program is being formed worked in order to eliminate or minimize the cost burden for the patients of this drug. As said, we have prepared those programs for us promoting access to the drug. Biogen and Eisai have clearly expressed their commitment to wide access to be provided to patients. So we like to bring the value of Adihelme to as many patients and their families as possible.
And so please press the button, the sharp button, N1, and we are going to connect you 1 by 1. So we are currently accepting the questions from the audience participating over the phone. Thank you very much. Let us begin with the first question. From Nomura Securities, Mr.
Kotani. This is Mr. Kotani from Nomura Securities. So please start. Thank you.
I am Kotani from Nomura Securities. I hope you can hear. So first of all, I have to say congratulations to you. Up until the approval, it has been a lot of difficulties and challenges. But as As Naito said, CRS B and you have been able to demonstrate the consistent the benefit.
So Biogen was very humble, but again, the accidents accidental, the outcome will be 1 over 10,000. And so this was not really discussed by the advisory report. But again, this kind of biomarker result was well reviewed. So I think that was good. And I would like to ask you a question about the bottleneck of the diagnosis.
Before the dosing, as series MMC's clinical, the judgment has to take place in an MRI or this CSF kind of testing I would have to take place to confirm the amyloid plug. So for the clinical evaluation, I think that you have the collaboration with CSP And also for this, the sales of testing LabCorp that you are collaborating with. So as to the bottleneck in terms of the diagnosing of the patients, do you think that you have been able to solve all the challenges? Or do you think you have some more that you need in terms of the support for the diagnosing. Doctor.
Kimura, who is in charge of the scientific aspect of neurology is going to respond. Thank you very much, Mr. Kotani. Kimura of the Neurology Business Group would like to respond to your questions. As you said amyloid accumulations in the brain.
To confirm this, currently, there are 3 different ways to achieve that. 1 is amyloid PET and another one is CSF testing and another one is the blood testing. As for the amyloid PET, there are 3 different choices that have already been approved, both in Japan, United States as well as in Europe and in U. S. MCI due to AD is also been in care approved to be used.
And MCI due to AD in Japan, it is not really approved for the use. But Alzheimer dementia, It is only for the indication of vast and dementia it is being approved. And also, it is not really covered in the insurance reimbursement. However, together with the members of the academia, and we are getting a lot of support. And so that was the other home that has been approved and therefore MCI due to this additional indication we'd like to get and also the insurance covers both in Japan And United States, we believe, would come very soon.
As for the pet trade, so for the number of pet, 1800 in the United States and also 600 units in Japan. So divided by the population both in Japan as well as in United States, it's going to be about 4 to 5 units per 1,000,000 populations. Of course, PET scales and FDG PET and also for the Kilser, tracing this kind of pet device can be used. And therefore, the number of pet would not be sufficient. And therefore, in order to supplement this, CSF diagnosing, especially A beta 42, the accumulations, we believe that it should be measured in CSF.
And so with the Fuji Revios CSRVD, both in Japan as well as in the United States, it is currently under review. And also, as Mr. Kotani mentioned, LDT laboratory development is as such it is being supplied. So it is not reimbursed, but level of antibodies or the Mayo Clinic and together with STEM LED testing that we would like to really offer as a sponsored program. And as for the CSC statistic, the phosphorylated tau testing needs to be done.
So for the AT in Japan, the phosphorylated tau measurement is being reimbursed. For us, it is not covered in the United States, but currently like Roche. For the phosphorylated tau and beta that they are trying to collect the ratio and they are getting the reimbursement. And therefore, with regard to the measurement of CS test, I'm sure that there's going to be significant advancement. And as for the blood testing.
Shimadzu has come up with this testing method and this is going to supplement the PET testing And it is being approved in Japan and in the United States. LDT, as a part of the LDT, it is already made available. And of course, it is not covered by the health insurance and also with SMEC and the simpler and less invasive blood testing that we would like to offer. And so at this point in time, of course, whether this can be offered as a full access, it is further uncertain, but cognigram's cognitive testing or CSF testing and PET and MRI. So by combining them in a systemic way, We think that we can improve on the access and we can reduce the burden for the patients.
Thank you.
If I may ask a follow-up question, Kimura san. No. Blood testing will come later. Currently available, PET and CSF. I think most testing will be derived from CSF.
Well, even with the Now for the 1,000,000 to 2,000,000 target patients as mentioned by Biogen, do you think that available testing will be Enough. And when it comes to the bullet testing, do you think it will be add on? Yes, that is correct. At the academic societies as well, Through combination of such available testing, how access to this drug can be expanded, that is already being considered. So rather than the number of units available, the combination will be more important.
This is the last question. When it comes to value based pricing, could you please explain further? I think for the If the HFR treatment, Scine Craft of Novartis, it is known, but the effect is low and then the price should be low. And then What is the measurement of the effect or benefits in order to verify the clinical benefits? There are two viewpoints.
One is to have very conservative severe one, faster progress advisory committee CDRS and with deterioration of over 8 points. And then for such patients, there will be no impacts, significant impacts. But ADONI, and as the historical data on the patients, in 6 months CDR SB deteriorate by 0.5% and over 1% worsening. And then for most of patients, the value will be covered by value based contracts. And so based on our model, how VIX, the target patient who recovered by this target the value based contract.
AD franchise, Mr. Shimizu in charge of AD franchise is going to respond to you. Can you hear? This is Shimizu speaking. Yes, I can hear you.
Thank you for your question, Mr. Kotani. It's a very good point. Currently, we are working with SIGNA as a main potential partner for value based contracts. Of course, there are many things that cannot be mentioned in writing.
However, for example, when administration is started, Of course, the titration will be the starting dose. And If there are any interruption of the drug because of the AE and then the value expected value is not to be returned to the patients, therefore, the related costs shall be returned. So inclusive of that, various scenarios are being considered after contract is concluded. We would like to update you. Thank you.
Not only AE, ADR, But also benefits or effect of the drug shall be considered as well, right? [SPEAKER UNIDENTIFIED COMPANY REPRESENTATIVE:] But also benefits or effect of the drug shall be considered as well, right? But regarding that point, it is being considered. Therefore, we are not in a position to respond to that specific question now. Thank you.
Understood.
From Citigroup Securities, Mr. Yamaguchi, please. I hope you can hear. Thank you. I have two questions.
The first question, I understand that this time it was an accelerated approval, So you have to carry out additional clinical trial. So as to the schedule of this clinical trial to come, Please give us further information on this. Thank you very much for your questions. So with regard to the question, Ivan Chan, Neurology Business President is going to respond. Ivan, please.
Thank you very much, Bianchi san, for this question. The FDA just posted the approval letter on the website. So you can see the approval letter. And in the approval letter, it's specified that To verify the clinical benefit of aducanumab, a randomized controlled trial to evaluate the efficacy of aducanumab compared to an appropriate control for the treatment of Alzheimer's disease will be conducted. And with regard to the schedule based on the agreement with the FDA written in the approval letter.
The final protocol will need to be submitted to the FDA next year in August. And the trial completion needs to be done by 2029 and the final report needs to be submitted to the FDA by 2,030. Thank you.
Thank you very much. May I ask second question? Yes, please. This is about the future, but BAN2401, which will come later. And could you please elaborate on this As well.
First one is biomarkers were the basis for the approval of aducanumab. And then similar approach may be taken for BAN2401. Do you think that it will be possible to obtain approval for that as well? But with the approval of aducanumab and 2,401 aducanumab, how are you going to have and differentiate these 2 drugs in the market? Could you please explain on these two points?
I would like to invite Ivan Chan to respond to your question.
Thank you very much for the question. Very good question. Firstly, for the first part to your question On BAN2401, as you know, the Phase III CLARITY AD trial For early AD, very similar population to the Aduhelm Phase 3 program. That trial completed enrollment back in March of this year. We expect readout of the trial in the Q2 of next fiscal year 2022 And we expect a very expedite process discussing with the FDA on those data.
So at this moment, we are very focused on completing and executing the CLARITY AD trial with the highest quality of data, a fully powered Phase III trial to enable our single pivotal a trial strategy for BAN2401 aiming to secure full approval based on Clarity AB. So that is our BAN2401 strategy. And with regard to the second part of your question on the differentiation of the 2, of course, you know very well Both antibodies target the aggregated form of the aggregated toxic form of amyloid beta, although the binding is a bit different between the 2, as you heard from CYO-ninety two earlier, of course, BAN2401 has preferential binding to protofibril. So, we do expect the profile in terms of efficacy, safety will be We will see some differences as any 2 antibodies in any class of therapy that would be expected. And based on the data, I think Eisai and Biogen will be very glad to have 2 therapies to address a rather heterogeneous population.
And again, not only clinical endpoints, but the biomarker profile of the 2 therapies down the road as we see the data will also play a very important role. We believe heading 2 will be very critical for Eifan and Daozun to be in the leadership position in this space for many years to come. Thank you.
Thank you very much. That is all and congratulations. The next question comes from Nippon Keizai Newspaper, Mr. Yamada. Thank you.
If I may, I would like to start. So first of all, I would like to say congratulations. So I understand that you received Accelerator's approval in the United States. But in the past, for the other products, those who have received accelerated approval. But again, there are some cases with which the approval have been rather difficult to come by in other markets, including European markets.
So how much are you certain about the approval to come in other regions? So with regard to the question, Ivan Chan is going to respond.
Thank you for the question. We are in active dialogue with the PMDA in Japan and the EMA in Europe and a few other regulatory agencies that we have filed And you are correct, different country does have somewhat different regulatory pathways to approve drugs, Whether we are talking about Japan or in the European Union, One thing I would say 2 things. 1, of course, is we stand behind the data package for aducanumab irrespective of which regulatory agency we are talking with. Number 2 is, it is true that it's been almost 2 decades for a new novel therapy for Alzheimer's disease and that's true not only in the United States is true everywhere else in the world, the unmet medical needs is enormous. So with these two points in mind, we will work very, very hard along with our partner Biogen in every single country that we have filed aducanumab to find a way to bring aducanumab to patients in those countries.
Thank you.
Thank you very much. Next person is from Credit Suisse Securities, Mr. Sakai. Mr. Sakai from Credit Suisse Securities.
Value based medicine, this concept has been explained by Mr. Naito at the time of information meeting as well, dollars 56,000 that means about 6,000,000 yen per year annual cost. And what are the pre assumptions? Up until 2025, you said that you will not increase the price for this truck. And this truck, How long this drug should be administered?
What is the preconditions, assumptions for coming up with this cost? And up until 'twenty nine may not be related to value base, but the Phase IV shall be conducted until 29. So considering all these costs, As per the materials provided by Biogen in the presentation, targeted patient, this term was used. 1,000,000 to 2,000,000 people patients are going to be targeted. So all these have been taken into account to come up with value based approach as the global value?
Or is it only related to the values considered in the United States? Thank you very much, Mr. Sakari. This is Naito speaking. In the modern pharmaceutical industry, as in the case of oncology area, but when it comes to the pricing for drugs, not based on costs, but rather the values which are expected to be brought about by the drug upon which value should be evaluated and price should be considered.
And that is the mainstream. And I believe that, that is the concept that is well received by the society at large. And assumptions, including various models like Markov model, there are various calculation models, mathematical models such as QUARI, concept of QUARI has been introduced. And for evaluation of costs are duly conducted. And after Considering all these factors, we came up with this they came up with this number.
And I would like to refrain from explaining specifics about the formula for calculation. But what is widely recognized or authorized in the society has been used as methodology. The equation for calculation has been selected to come up with this threshold within which price was calculated. I think that is what I can say. Thank you.
Understood. Getting approval on this drug, I think that you have a kind of a spell of mission. So I hope that you will do your best in order to deliver to what has been promised.
Next question comes from Mr. Yonezawa of Yumiri Newspaper. I hope you can hear me. Thank you. I'm Yonezawa from Yumirui Newspaper.
So this is my questions to Mr. Naito. So as for this contribution of this drug to your bottom line, from when do you think that you can achieve the contributions to your profitability? And how do you view the possibility of this becoming the blockbuster? Thank you very much, Mr.
Inizawa. This is Maito speaking. So with regard to this drug, As I have been trying to discuss, again, this is really the drug that will require The A beta confirmation to confirm the aggregation of A beta. So as we discussed, we need PET And CFS kind of the testing by overcoming this process that we can find the eligible patients. So in a way, this is not really another common drug, but this is truly a specialty drug.
So that's how this product is recognized. And therefore, as Biogen says, In the United States, you're talking about 1,000,000 to 2,000,000 of patients. And also in Japan, Probably it should be around 1,000,000 of the patients that would become target initially for this treatment. And of those potential patients' EBITDA confirmation would need to be done for this PET for the CSF testing. And so we need to really come up with a good forecast as to the proportion of the patients who will eligible.
And so for the first round of patients who will be placed under this treatment. I do not really expect any large kind of sales revenues or probability coming from such a first round of patients, but as we have better infrastructures for testing and also as was mentioned today, If blood testing can be used for the confirmation of A beta plug, and then that should certainly make it possible for far larger the patients becoming eligible for this treatment. And it is really at that point in time that this may really be able to unleash the potential that it has to make the significant contributions to our bottom line? Thank you.
Well, it is It's actually the time to end today's meeting. So we would like to end today's meeting, and we would like to Close today's conference call. Thank you very much for taking time out of your busy schedule to take part in this meeting. Hope you will continue to support us. Thank you.