Now it is time to start meeting Eisai Company Limited conference call. Today, we'd like to talk about the accelerated approval of aducanumab given by U.S. FDA. Now, without further ado, I'd like to invite Mr. Naito, our CEO, to start.
Thank you. This is Naito speaking. This time around, ADUHELM has been granted approval from U.S. FDA. Upon that approval, the first thing that came to my mind was the FDA's approval of ARICEPT on November 25th, 1996. From the date of ARICEPT approval to June 7th, 2021, approximately 25 years have passed, words cannot describe how we are deeply moved through this challenging journey to finally have the first in-class drug that can target an underlying pathology of Alzheimer's disease.
A review of the prescribing 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. 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 of treatment, and improving the accuracy of diagnosis.
The prescribing information of ARICEPT in 1996 at the time of approval described the results of the ADAS-Cog and CIBIC-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 had 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-Cog 13, ADCS-ADL-MCI, and NPI-10 as primary, secondary, and tertiary endpoints in a multi-layered 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, ADUHELM showed the reduction of the amyloid pathology.
In its prescribing information, comprehensive evaluation of both cognitive and functional aspects like CDR-SB and relating endpoints such as cognitive function, quality of life, and BPSD or NPI-10 were described. I believe that difference between the two prescribing information is a true indication of the innovative revolution of biomarker research and clinical science over the past quarter-century. Diagnostic advances have also been extremely remarkable. Accuracy of MRI has dramatically improved, and the innovations in AD diagnosis and pathological change assessment brought about by probe research in molecular imaging such as PET are prominent. 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 42:40 ratio for tau, p-tau181 and p-tau217, and a neurodegeneration NfL or neurofilament light or t-tau neurogranin 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. 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. What is the value of Alzheimer's disease treatment targeting underlying pathology in general? For a quarter of a century, Eisai has been working closely with 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 the so-called value-based pricing. Values, benefits, and various costs to 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.
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 two separate issues. Building the price that well reflects 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. Also, this is the essential as a concrete indicator of the innovation. Whereas the policy to ensure the access 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. We need to put in place various support programs and support mechanism.
Especially, we need to be able to provide these medical services to those who are relatively underserved in the social system, such as low-income populations. We need to focus on the very comprehensive initiative. Through the pricing policies, we need to represent the true value of the medicines. Through the access policies, we need to be able to deliver a product to the patients who are in need of this. These two policies would not be contradicting with each other, and it is very important to achieve both goals. Again, it is probably not too much of an exaggeration to say that it would be the overarching mission of the modern pharmaceutical industry to achieve both of these goals. As for the access policy of ADUHELM, we have to pay close attention to the coping situations of various insurance programs in the U.S.
Again, the underserved communities. For them, we have to really think about the various measures to overcome healthcare divide in those communities, we want to collaborate with the PHAs or the other retail pharmacies or NAFC. 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 providers contract. Also, we will be carrying out the free CSF diagnostic testing with the providers, and we will keep the price for the initial four years. Depending upon the progress of our review, we will be looking into the access policy in Asian region on a timely basis.
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 financing institutions, we will try to reduce the burden for the patients. We would like to devise the reinsurance scheme with the insurance. For these low-income populations, want to consider the tiered pricing or the collaboration with NGOs to provide the medicines. Through the mutual system, we would like to consider various innovative models. Currently, as the ecosystem platform, we are building the EUP, Eisai Universal Platform, and would like to further accelerate our efforts in this regard. With Alzheimer's disease modifying the treatment and medicines, they are certainly the core of the solution package of EUP.
Our goal of EUP is to free the people of the worries and anxieties. They would like to lead a full life, even though they may be suffering from dementias, or they would not want to cause any troubles to their family members, but would not want to see the further aggravation of their conditions. Based upon the various science and clinical evidence, it would be possible for us to offer many different kinds of solutions. Going forward, we will be able to obtain the patient's biomarker data, and that should enable us to indicate a better guidance advice to the healthcare providers, and also through the provision of various services and benefits through this disease awareness and diagnosis and treatment and care. We believe that we should be able to make a step forward for the resolution of the challenge that we face today.
Last but not least, we are also currently working on the development of anti-protofibril lecanemab for the new anti-MTBR tau antibody E2814 for new TrkA positive allosteric modulator E2511. In all of these developments, we are currently working on the disease-modifying candidates that will work on the different parts of the pathophysiology of Alzheimer's disease. Based upon that, the patient's biomarker data, by properly using these drugs, we think that we can come closer to the fundamental treatment of Alzheimer's disease. Going forward, we would like to continue this utmost effort so that we can continue to contribute to the patients and their family members by freeing the patients of their worries.
Thank you. Shimizu is going to talk about the pricing and access. Shimizu is the Group Officer of AD Franchise Special Mission.
Well, thank you very much for waiting. My name is Shimizu. I am in charge of the AD Franchise. I am 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 caregivers, in order to increase the value and benefits and in order to reduce the costs related to various aspects of the disease. Considering all these, pricing is to come. Working on the pathology of Alzheimer's disease. We believe that pricing should be fair and reasonable considering this is the first in class, bringing about such benefits. In the U.S., as you know, every year the price is being increased. For ADUHELM, we are going to keep the price of ADUHELM for four years unchanged.
In order, while reflecting the multifaceted values of the drug into the price, and when it comes to expanding the access by patients to ADUHELM and a 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. Most of the patients with Alzheimer's disease are 65 years old or over, and according to our calculation, about 85% or over of the patients are covered by Medicare insurance. Most of the Medicare-insured people have the additional rider insurance policy. Therefore, 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.
Medicare, if they are disabled and if they have any financial difficulties and then draw eligible 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 were no rider policy purchased by those patients. For such patients, o n individual cases, we are going to provide consultation services for insurance coverage on an individual basis.
Among them, because of the economic difficulties, if they are not able to pay or afford the drugs, there will be a free-of-charge provision of the drugs if conditions are met. For those underserved community, in order to improve the health equity and U.S. Department of Veterans Affairs, VHA, and so forth, as has been mentioned in release, we are now finalizing the contract with them. With CVS Health, we are now trying to bring into the community in order to have the cognitive screening. NAFC, National Association of Free and Charitable Clinics, with whom we are collaborating, about 1,400 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, a private sector insurer is covering the insurance for patients. In order to reduce the out-of-pocket payment for the patients, a co-pay program is being formed, worked out in order to eliminate or minimize the cost burden for the patients of this drug. As said, we have prepared those programs for promoting access to the drug. Biogen and Eisai have clearly expressed their commitment to wide access to be provided to patients. We'd like to bring the value of ADUHELM to as many patients and their families as possible.
Now we'd like to start the Q&A session. We can receive the questions from those participants participating from the phone. Please press the sharp button and one, we are going to connect you one by one. 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. Kohtani. This is Mr. Kohtani from Nomura Securities. Please start.
Thank you. I am Kohtani from Nomura Securities. Happy to be here. First of all, I have to say congratulations to you. Up until the approval, there's been a lot of difficulties and challenges, but as Shuhei just said, CDR-SB, and you have been able to demonstrate the consistent benefit. Biogen was very humble. Again, the accidental outcome of the 1/ 10,000, and so this was not really discussed by the advice report. Again, this kind of biomarker result was well-reviewed, so I think that was good. I would like to ask you a question about the bottleneck of the diagnosis before the dosing. As there is an MMSE clinical, the judgment has to take place, an MRI or this CSF kind of testing would have to take place to confirm the amyloid plaque.
For the clinical evaluation, I think that you have the cooperation with Cogstate and also for this CSF testing, you have ADx NeuroSciences that you are collaborating with. 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? It's Dr. Kimura, who is in charge of the scientific aspect of neurology, is going to respond.
Thank you very much, Mr. Kohtani. Kimura of the Neurology Business Group would like to respond to your questions.
As you have said, amyloid accumulations in the brain. To confirm this, currently, there are three different ways to achieve that. One is amyloid PET, and another one is CSF testing, and another one is the blood testing.
As for the amyloid PET, there are three different traces that have already been approved, both in Japan, U.S., as well as in Europe. In U.S., MCI due to AD is also being approved to be used. MCI due to AD in Japan, it is not really approved for the use. Alzheimer dementia, it is only for the indication of Alzheimer 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. That was the ADUHELM that has been approved, and therefore, MCI due to this additional indication we'd like to get, and also the insurance coverage both in Japan and U.S., we believe would come very soon.
As for the PET tracer, for the number of PET, 1,800 in the U.S. and 600 units in Japan. Divided by the population both in Japan as well as in the U.S., it's going to be about 4-5 units/ 1 million populations. Of course, PET scales from FDG PET, for the cancer tracing, this kind of PET device can be used. Therefore, the number of PET would not be sufficient. Therefore, in order to supplement this CSF diagnosing, especially A-beta 42 the accumulations. We believe that it should be measured in CSF. With the Fujirebio CSF ug, both in Japan as well as in the U.S., it is currently under review. As Mr. Kohtani mentioned, LDT, laboratory developed test. As such, it is being supplied.
It is not reimbursed, but level of amyloid-beta or the Mayo Clinic and together with them, LDT testing, that we would like to really offer as a sponsored program. As for the CSF testing, the phosphorylated tau testing needs to be done. For the AD in Japan, the phosphorylated tau measurement is being reimbursed, whereas it is not covered in the U.S., but currently like Roche for the p- tau and the amyloid-beta, that they are trying to collect the ratio, and they are getting the reimbursement. Therefore, with regard to the measurement of CSF, I'm sure that there's going to be significant advancement. As for the blood testing, Shimadzu has come up with this testing method, and this is going to supplement the PET testing, and that is being approved in Japan and in the U.S.
LDT, as a part of the LDT, it is already made available. Of course, it is not covered by the health insurance and also with this mass spec and the simpler and less invasive blood testing that we would like to offer. At this point in time, of course, whether this can be offered as a full access, it is still uncertain. When it comes to 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. Now, blood testing will come later. They're currently available, PET and CSF. I think most testing will be derived from CSF. Well, even with the Now, for the 1 million-2 million target patients as mentioned by Biogen, do you think that available testing will be enough? When it comes to the blood testing, do you think it will be around?
Yes, that is correct. At the academic societies as well. The third combination of such available testing, how access to this drug can be expanded, that is already being considered. Rather than a 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 SMA treatment, Zolgensma of Novartis, it is known, but the effect is low, and then the price should be low.
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 progressor advisory committees and CDR-SB with deterioration of over 8 points. For such patients, there will be no significant impact. Anyway, as the historical data on the patients, six months and CDR-SB, they deteriorate by 0.5%, over 1% worsening. For most of patients, the value will be covered by value-based contracts. Based on our model, how big the target patient who will be covered by this value-based contract? AD Franchise.
Shimizu in charge of AD Franchise is going to respond to you.
Can you hear Shimizu speaking?
Yes, I can hear you.
Thank you for your question, Mr. Kohtani. It's a very good point. Currently, we are working with Cigna 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. If there are any interaction of the drug because of the AE, the expected value is not to be returned to the patients, the related costs shall be returned. Inclusive of that, various scenarios are being considered. After contract is concluded, we'd like to update you. Thank you.
Not only AE, ADR, but also benefits or effect of the drug shall be considered as well, right? Regarding that point, it is still 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. As to the schedule of this clinical trial to come, please give us further information on this. Thank you very much for your questions. With regard to the question
Ivan Cheung, Neurology Business President, is going to respond. Ivan, please.
Thank you very much, Yamaguchi-san, for this question. The FDA just posted the approval letter on the website, so you can see the approval letter. In the approval letter it is specified that to verify the clinical benefits 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. With regard to the schedule, based on the agreement with the FDA, as written in the approval letter, the final protocol will need to be submitted to the FDA next year in August. The trial completion needs to be done by 2029, and the final report needs to be submitted to the FDA by 2030. Thank you.
Thank you very much. May I ask a 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 the biomarkers were the basis for the approval of aducanumab, and then a similar approach may be taken for BAN2401. Do you think that it will be possible to obtain approval for that as well? With the approval of aducanumab and BAN2401, how are you going to differentiate these two drugs in the market? Could you please explain on these two points?
I would like to invite Ivan Cheung 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 III program. That trial completed enrollment back in March of this year. We expect readout of the trial in the second quarter of next fiscal year 2022, and we expect a very expedited process discussing with the FDA on those data. 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 trial strategy for BAN2401, aiming to secure a full approval based on Clarity AD. That is our BAN2401 strategy.
With regard to the second part of your question on the differentiation of the two, of course, you know very well both antibodies target the aggregated toxic form of amyloid-beta. Although the binding is a bit different between the two. As you heard from Naito earlier, of course, BAN2401 has preferential binding to protofibril. We do expect the profile in terms of efficacy, safety, we will see some differences as any two antibodies in any class of therapy. That would be expected. Based on the data, I think Eisai and Biogen will be very glad to have two therapies to address a rather heterogeneous population. Again, not only clinical endpoints, but the biomarker profile of the two therapies down the road as we see the data will also play a very important role.
We believe having two will be very critical for Eisai and Biogen to be in the leadership position in this space for many years to come. Thank you.
Thank you very much. That is all. Congratulations.
The next question comes from the Nihon Keizai Shimbun, Mr. Yamada.
Thank you. If I may, I'd like to start. First of all, I would like to say congratulations. I understand that you received accelerated approval in the U.S., but in the past, for the other products, those who have received accelerated approval. Again, there are some cases with which the approval have been rather difficult to come by in other markets, including European markets. How much are you certain about the approval to come in other regions?
With regard to the question, Ivan Cheung 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 aducanumab. You are correct. Different countries do have somewhat different regulatory pathways to approve drugs, whether we're talking about Japan or in the European Union. I would say two things. One, of course, is we stand behind the data package for aducanumab, irrespective of which regulatory agency we are talking with. Number two is, it is true that it's been almost two decades for a new novel therapy for Alzheimer's disease, and that's true not only in the United States. It's true everywhere else in the world. The unmet medical need is enormous.
With these two points in mind, we will work very hard along with our partner, Biogen, in every single country that we have filed aducanumab, to find a way to bring ADUHELM to patients in those countries. Thank you.
Thank you very much. The next person is from Credit Suisse Securities, Mr. Sakai. Mr. Sakai from Credit Suisse Securities, please have the floor.
Thank you very much. Value-based medicine. This concept has been explained by Mr. Naito at the time of the information meeting as well, $56,000. That means about JPY 6 million per year, annual cost. What are the pre-assumptions? Up until 2025, you said that you will not increase the price for this drug. This drug, how long this drug should be administered? What is the pre-conditions assumptions for coming up with this cost? Up until 2029 may not be related to value-based, but the phase IV shall be conducted until 2029. Concerning all these costs, as per the materials provided by Biogen in the presentation, targeted patient, this term was used.
1 million- 2 million people, patients are going to be targeted. 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. Sakai. This is Naito speaking. In the modern pharmaceutical industry, as in the case of oncology area, 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 a value should be evaluated and price should be considered. That is the mainstream. I believe that is the concept that is well-received by the society at large. Assumptions, including various models like Markov model. There are various calculation models, mathematical models such as QALY. Concept of QALY has been introduced. For evaluation of costs are duly conducted. After considering all these factors, they came up with this number.
I would like to refrain from explaining the 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 sense of mission, so I hope that you will do your best in order to deliver to what has been promised. Thank you.
Next question comes from Mr. Yonezawa of Yomiuri Shimbun. I hope you can hear me.
Thank you. I'm Yonezawa from Yomiuri Shimbun. This is my question to Mr. Naito. 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? How do you view the possibility of this becoming the blockbuster?
Thank you very much, Mr. Yonezawa. This is Naito speaking. 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. As we discussed, we need a PET and the CSF kind of the testing, and by overcoming this process that we can find the eligible patients. In a way, this is not really another common drug, but this is truly a specialty drug. That's how the product is recognized.
Therefore, as Biogen says, in the U.S., they're talking about 1 million- 2 million patients. Also in Japan, probably it should be around 1 million patients that would become target initially for this treatment. Of those potential patients, either confirmation would need to be done for this PET or the CSF testing. We need to really come up with a good forecast as to the proportion of the patients who will become eligible. 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 profitability coming from such a first round of patients.
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 plaque, then that should certainly make it possible for far larger patients becoming eligible for this treatment. 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.
It is actually the time to end today's meeting, so we'd like to end today's meeting and we'd 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.