by codm | Mar 20, 2023 | Newsletter
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Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) today announced the publication of updated results from an evaluation estimating the societal value of anti-amyloid-beta (Aβ) protofibril* antibody lecanemab (generic name, U.S. brand name: LEQEMBI™) in people living with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and mild AD (collectively known as early AD) using data from the Phase 3 clinical study, Clarity AD by applying a validated disease simulation model, AD Archimedes Condition Event (AD ACE) model1,2,3 from the healthcare payer and societal perspectives in the United States, in the peer-reviewed journal Neurology and Therapy
. While the healthcare payer perspective focuses on direct care costs (e.g., outpatient and inpatient services, medications, intervention costs, nursing home and home healthcare services), the societal perspective further considers societal costs (e.g., productivity loss and informal care costs).
The findings of this academic paper about the societal value of lecanemab in the U.S. was used to inform the development of “Eisai’s Approach to Pricing for LEQEMBI™ (lecanemab), a Treatment for Early Alzheimer’s disease, Sets forth Our Concept of “Societal Value of Medicine” in Relation to “Price of Medicine” that was described in our press release issued on January 7, 2023 (Japan Standard Time).
This model-based simulation was conducted using the results of the Phase 3 Clarity AD study evaluating the efficacy and safety of lecanemab for early AD with confirmed amyloid pathology as well as published literature.
Lecanemab+SoC (standard of care**) was predicted to result in a gain of 0.61 quality-adjusted life-years*** (QALY)s and a decrease in total non-treatment costs of $6,263 per person from the healthcare payer perspective (Societal perspective: 0.64 QALYs gain and $7,451 decrease) compared to the SoC for patients with early AD who have confirmed presence of amyloid pathology. The mean duration of lecanemab treatment in this simulation was 3.91 years. The model estimated that the annual value of lecanemab for the U.S. payer perspective was $18,709 to $35,678 ($19,710 to $37,351 for societal perspective) at the willingness-to-pay (WTP) threshold of $100,000 to $200,000 per QALY gained, respectively. A modified societal perspective at $200,000 WTP threshold per QALY gained is used in the U.S. when the societal cost of the disease is large with substantial impacts on caregivers, such as AD. The paper concluded that lecanemab treatment would improve health and humanistic (quality of life) outcomes and reduce economic burden for patients and caregivers in early AD.
“The outcomes of this simulation quantitatively demonstrate the societal value of lecanemab, showing that lecanemab provides significant impact not only to people living with early AD and their caregivers, but also to society as a whole. While a broader range of values was considered, the severity-adjusted WTP threshold of $200,000 per QALY gained accurately reflects the societal value of lecanemab,” said Ivan Cheung , Senior Vice President, and Global Alzheimer’s Disease Officer, Eisai Co., Ltd., Chairman and CEO, Eisai Inc. “Eisai will continue to transparently and expeditiously publish data and information about lecanemab in order to transparently discuss its societal value for people and countries around the globe.”
Lecanemab was approved under the accelerated approval pathway in the U.S. and was launched in the U.S. on January 18, 2023. The accelerated approval was based on Phase 2 data that demonstrated that lecanemab reduced the accumulation of Aβ plaque in the brain, a defining feature of AD, and its continued approval may be contingent upon verification of lecanemab’s clinical benefit in a confirmatory trial. The U.S. Food and Drug Administration (FDA) determined that the results of Clarity AD can serve as the confirmatory study to verify the clinical benefit of lecanemab.
In the U.S., Eisai submitted a supplemental Biologics License Application (sBLA) to the FDA for approval under the traditional pathway on January 6, 2023. On March 3, 2023, the FDA accepted Eisai’s sBLA based on the Clarity AD clinical data, and the lecanemab application has been granted Priority Review, with a Prescription Drug User Fee Act (PDUFA) action date of July 6, 2023. Eisai submitted an application for manufacturing and marketing approval to the Pharmaceuticals and Medical Devices Agency (PMDA) on January 16, 2023, in Japan. The Priority Review was granted by the Ministry of Health, Labour and Welfare (MHLW) on January 26, 2023. Eisai utilized the prior assessment consultation system of PMDA, with the aim of shortening the review period for lecanemab. In Europe, Eisai submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) on January 9, 2023, which was accepted on January 26, 2023. In China, Eisai initiated submission of data for a BLA to the National Medical Products Administration (NMPA) of China in December 2022, and the Priority Review was granted on February 27, 2023.
Eisai serves as the lead of LEQEMBI development and regulatory submissions globally with both Eisai and Biogen Inc. co-commercializing and co-promoting the product and Eisai having final decision-making authority.
* Protofibrils are large Aβ aggregated soluble species of 75-5000 Kd.4
** Standard of Care (SoC) for AD currently consists of lifestyle modifications and pharmacologic treatment of symptoms.
*** The quality-adjusted life year (QALY) is a measure of the value of health outcomes. Since health is a function of length of life (i.e., quantity) and quality of life (QOL), the QALY was developed as an attempt to combine the value of these attributes into a single index number. One QALY equates to one year in perfect health. QOL scores range from 1 (full health) to 0 (dead). For example, a new intervention may increase length of life by 3 years and improve quality of life by 70% (QALY score of 2.1) compared to an existing intervention that may increase length of life by 3 years and only improve QOL by 50% (QALY score of 1.5), the incremental QALY for this new intervention will be 0.6 QALYs.
1 Kansal AR, Tafazzoli A, Ishak KJ, Krotneva S. Alzheimer’s disease Archimedes condition-event simulator: Development and validation. Alzheimers Dement (NY). 2018;4:76-88. Published 2018 Feb 16. doi:10.1016/j.trci.2018.01.001.
2 Tafazzoli A and Kansal A. Disease simulation in drug development, External validation confirms benefit in decision making. The Evidence Forum. 2018.
https://www.evidera.com/wp-content/uploads/2018/10/07-Disease-Simulation-in-Drug-Development_Fall2018.pdf
3 Tafazzoli A, Weng J, Sutton K, et al. Validating simulated cognition trajectories based on ADNI against 436 trajectories from the National Alzheimer’s Coordinating Center (NACC) dataset. 11th edition of Clinical Trials on 437 Alzheimer’s Disease (CTAD); Barcelona, Spain: 2018. https://www.evidera.com/wp-content/uploads/2018/10/07-Disease-Simulation-in-Drug-Development_Fall2018.pdf
4 Söderberg, L., Johannesson, M., Nygren, P. et al. Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer’s Disease. Neurotherapeutics (2022). https://doi.org/10.1007/s13311-022-01308-6. Accessed February 9, 2023
Media Inquiries:
| Eisai |
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Eisai Co., Ltd.
Public Relations Department
Eisai Inc. (U.S.)
Libby Holman
Eisai Europe, Ltd.
(Europe, Australia, New Zealand and Russia)
EMEA Communications Department
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[Notes to editors]
- 1. About Lecanemab
Lecanemab (Brand Name in the U.S.: LEQEMBI™) is the result of a strategic research alliance between Eisai and BioArctic. Lecanemab is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). In the U.S., LEQEMBI was granted accelerated approval by the U.S. Food and Drug Administration (FDA) on January 6, 2023. LEQEMBI is indicated for the treatment of Alzheimer’s disease (AD) in the U.S. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. This indication is approved under accelerated approval based on reduction in Aβ plaques observed in patients treated with LEQEMBI. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.
Please see full Prescribing Information.
Eisai has completed lecanemab subcutaneous bioavailability study, and subcutaneous dosing is currently being evaluated in the Clarity AD (Study 301) OLE.
Since July 2020 the Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains, is ongoing. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer’s Clinical Trial Consortium that provides the infrastructure for academic clinical trials in AD and related dementias in the U.S, funded by the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen.
Since January 2022, the Tau NexGen clinical study for Dominantly Inherited AD (DIAD), that is conducted by Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, is ongoing.
2. About the Collaboration between Eisai and Biogen for AD
Eisai and Biogen have been collaborating on the joint development and commercialization of AD treatments since 2014. Eisai serves as the lead of lecanemab development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.
3. About the Collaboration between Eisai and BioArctic for AD
Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development and commercialization of AD treatments. Eisai obtained the global rights to study, develop, manufacture and market lecanemab for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercialization agreement on the antibody lecanemab
by codm | Mar 14, 2023 | Newsletter
EISAI IS PROUD TO SUPPORT U.S. VETERANS LIVING WITH EARLY STAGES OF ALZHEIMER’S DISEASE AND WILL CONTINUE TO TRANSPARENTLY SHARE OUR HIGH-QUALITY DATA WITH THE VHA
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Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that the U.S. Veterans’ Health Administration (VHA) is providing coverage of LEQEMBI™ (lecanemab-irmb) to veterans living with early stages of Alzheimer’s disease (AD). VHA healthcare professionals meeting the criteria set forth by the VHA can prescribe LEQEMBI to veterans who fit the VHA’s criteria and the U.S. Food and Drug Administration’s (FDA) current label. The VHA’s careful consideration and timely action to make LEQEMBI available approximately two months after the FDA approved LEQEMBI under the accelerated approval pathway shows its continued commitment to veterans living with AD.
If approved under the traditional pathway, the FDA will update the label for LEQEMBI, which will include new data that has been evaluated by the FDA. Eisai looks forward to sharing additional high-quality data as it becomes available and to continuing discussions with the VHA as the company prepares for the FDA’s potential conversion of LEQEMBI’s accelerated approval to a traditional approval. Eisai is proud of and humbled by the opportunity to support U.S. veterans as we strive to fulfill our human health care (hhc) mission.
LEQEMBI is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibrils*) and insoluble forms of amyloid beta (Aβ), LEQEMBI was approved in the U.S. under the Accelerated approval Pathway for the treatment of AD on January 6, 2023, and was launched in the U.S on January 18, 2023. Treatment with LEQEMBI should only be initiated in patients with mild cognitive impairment or mild dementia stage of disease and confirmed presence of Aβ pathology.
The Accelerated approval was based on Phase 2 data that demonstrated that LEQEMBI reduced the accumulation of Aβ plaque in the brain, a defining feature of AD, and its continued approval may be contingent upon verification of LEQEMBI’s clinical benefit in a confirmatory trial. The FDA has determined that the results of Clarity AD will serve as the confirmatory study to verify the clinical benefit of LEQEMBI.
On the same day that LEQEMBI received its Accelerated approval, Eisai submitted the supplemental Biologics License Application (sBLA) to the FDA for approval under the Traditional pathway. The sBLA was accepted by the FDA on March 3, 2023 and granted Priority Review with a Prescription Drug User Fee Act (PDUFA) date of July 6, 2023. The sBLA is based on the findings from Eisai’s recently published large, global confirmatory Phase 3 clinical trial, Clarity AD. LEQEMBI met the primary endpoint and all key secondary endpoints with highly statistically significant results. In November 2022, results of the Clarity AD study were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference and simultaneously published in the peer-reviewed medical journal, The New England Journal of Medicine.
Eisai serves as the lead of LEQEMBI development and regulatory submissions globally with both Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority.
* Protofibrils are large Aβ aggregated soluble species of 75-500 Kd.1
To learn more, visit http://www.leqembi.com/.
INDICATION, DOSAGE AND ADMINISTRATION, AND IMPORTANT SAFETY INFORMATION IN THE U.S.
INDICATION
LEQEMBI is indicated for the treatment of Alzheimer’s disease. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. This indication is approved under accelerated approval based on reduction in amyloid beta plaques observed in patients treated with LEQEMBI. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Amyloid Related Imaging Abnormalities
LEQEMBI can cause amyloid related imaging abnormalities-edema (ARIA-E) and -hemosiderin deposition (ARIA-H). ARIA-E can be observed on MRI as brain edema or sulcal effusions, and ARIA-H as microhemorrhage and superficial siderosis. ARIA is usually asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, rarely can occur. Reported symptoms associated with ARIA may include headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms associated with ARIA usually resolve over time.
ARIA Monitoring and Dose Management Guidelines
Obtain recent (within one year) brain magnetic resonance imaging (MRI) prior to initiating treatment with LEQEMBI. Obtain an MRI prior to the 5th, 7th, and 14th infusions.
Recommendations for dosing in patients with ARIA-E and ARIA-H depend on clinical symptoms and radiographic severity. Depending on ARIA severity, use clinical judgment in considering whether to continue dosing, temporarily discontinue treatment, or permanently discontinue LEQEMBI.
Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment with LEQEMBI. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including MRI if indicated. If ARIA is observed on MRI, careful clinical evaluation should be performed prior to continuing treatment.
There is no experience in patients who continued dosing through symptomatic ARIA-E or through asymptomatic, but radiographically severe, ARIA-E. There is limited experience in patients who continued dosing through asymptomatic but radiographically mild to moderate ARIA-E. There are limited data in dosing patients who experienced recurrent ARIA-E.
Incidence of ARIA
In Study 1 (Study 201), symptomatic ARIA occurred in 3% (5/161) of LEQEMBI-treated patients. Clinical symptoms associated with ARIA resolved in 80% of patients during the period of observation.
Including asymptomatic cases, ARIA was observed in LEQEMBI: 12% (20/161); placebo: 5% (13/245). ARIA-E was observed in LEQEMBI: 10% (16/161); placebo: 1% (2/245). ARIA-H was observed in LEQEMBI: 6% (10/161); placebo: 5% (12/245). There was no increase in isolated ARIA-H for LEQEMBI compared to placebo.
Intracerebral hemorrhage >1 cm in diameter was reported after one treatment in LEQEMBI: 1 patient; placebo: zero patients. Events of intracerebral hemorrhage, including fatal events, in patients taking LEQEMBI have also been reported in other studies.
Apolipoprotein E ε4 (ApoE ε4) Carrier Status and Risk of ARIA
In Study 1, 6% (10/161) of patients in the LEQEMBI group were ApoE ε4 homozygotes, 24% (39/161) were heterozygotes, and 70% (112/161) were noncarriers.
The incidence of ARIA was higher in ApoE ε4 homozygotes than in heterozygotes and noncarriers among patients treated with LEQEMBI. Of the 5 LEQEMBI-treated patients who had symptomatic ARIA, 4 were ApoE ε4 homozygotes, 2 of whom experienced severe symptoms. An increased incidence of symptomatic and overall ARIA in ApoE ε4 homozygotes compared to heterozygotes and noncarriers in LEQEMBI-treated patients has been reported in other studies.
The recommendations on management of ARIA do not differ between ApoE ε4 carriers and noncarriers.
Consider testing for ApoE ε4 status to inform the risk of developing ARIA when deciding to initiate treatment with LEQEMBI.
Radiographic Findings
The majority of ARIA-E radiographic events occurred early in treatment (within the first 7 doses), although ARIA can occur at any time and patients can have more than 1 episode. The maximum radiographic severity of ARIA-E in patients treated with LEQEMBI was mild in 4% (7/161) of patients, moderate in 4% (7/161) of patients, and severe in 1% (2/161) of patients. Resolution on MRI occurred in 62% of ARIA-E patients by 12 weeks, 81% by 21 weeks, and 94% overall after detection. The maximum radiographic severity of ARIA-H microhemorrhage in patients treated with LEQEMBI was mild in 4% (7/161) of patients and severe in 1% (2/161) of patients; 1 of the 10 patients with ARIA-H had mild superficial siderosis.
Concomitant Antithrombotic Medication and Other Risk Factors for Intracerebral Hemorrhage
Patients were excluded from enrollment in Study 1 for baseline use of anticoagulant medications. Antiplatelet medications such as aspirin and clopidogrel were allowed. If anticoagulant medication was used because of intercurrent medical events that required treatment for ≤4 weeks, treatment with LEQEMBI was to be temporarily suspended.
Most exposures to antithrombotic medications were to aspirin; few patients were exposed to other antiplatelet drugs or anticoagulants, limiting any meaningful conclusions about the risk of ARIA or intracerebral hemorrhage in patients taking other antiplatelet drugs or anticoagulants. Because intracerebral hemorrhages >1 cm in diameter have been observed in patients taking LEQEMBI, additional caution should be exercised when considering the administration of antithrombotics or a thrombolytic agent (e.g., tissue plasminogen activator) to a patient already being treated with LEQEMBI.
Patients were excluded from enrollment in Study 1 for the following risk factors for intracerebral hemorrhage: prior cerebral hemorrhage >1 cm in greatest diameter, more than 4 microhemorrhages, superficial siderosis, evidence of vasogenic edema, evidence of cerebral contusion, aneurysm, vascular malformation, infective lesions, multiple lacunar infarcts or stroke involving a major vascular territory, and severe small vessel or white matter disease. Caution should be exercised when considering the use of LEQEMBI in patients with these risk factors.
Infusion-Related Reactions
Infusion-related reactions were observed in LEQEMBI: 20% (32/161); placebo: 3% (8/245); and the majority of cases in LEQEMBI-treated patients (88%, 28/32) occurred with the first infusion. All infusion-related reactions were mild (56%) or moderate (44%) in severity. Infusion-related reactions resulted in discontinuations in 2% (4/161) of patients treated with LEQEMBI. Symptoms of infusion-related reactions included fever and flu-like symptoms (chills, generalized aches, feeling shaky, and joint pain), nausea, vomiting, hypotension, hypertension, and oxygen desaturation.
After the first infusion, 38% of LEQEMBI-treated patients had transient decreased lymphocyte counts to <0.9 x109/L compared to 2% on placebo, and 22% of LEQEMBI-treated patients had transient increased neutrophil counts to >7.9 x109/L compared to 1% on placebo.
In the event of an infusion-related reaction, the infusion rate may be reduced, or the infusion may be discontinued, and appropriate therapy initiated as clinically indicated. Prophylactic treatment with antihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids prior to future infusions may be considered.
ADVERSE REACTIONS
In Study 1, 15% of LEQEMBI-treated patients, compared to 6% of placebo-treated patients, stopped study treatment because of an adverse reaction. The most common adverse reaction leading to discontinuation of LEQEMBI was infusion-related reactions that led to discontinuation in 2% (4/161) of patients treated with LEQEMBI compared to 1% (2/245) of patients on placebo.
The most common adverse reactions reported in ≥5% of patients treated with LEQEMBI (N=161) and ≥2% higher than placebo (N=245) in Study 1 were infusion-related reactions (LEQEMBI: 20%; placebo: 3%), headache (LEQEMBI: 14%; placebo: 10%), ARIA-E (LEQEMBI: 10%; placebo: 1%), cough (LEQEMBI: 9%; placebo: 5%), and diarrhea (LEQEMBI: 8%; placebo: 5%).
Please see full Prescribing Information
Media Contacts:
| Eisai |
|
Eisai Co., Ltd.
Public Relations Department
Eisai Inc. (U.S.)
Libby Holman
Eisai Europe, Ltd.
(Europe, Australia, New Zealand and Russia)
EMEA Communications Department
|
[Notes to editors]
About LEQEMBITM (lecanemab-irmb)
LEQEMBITM (lecanemab-irmb) is the result of a strategic research alliance between Eisai and BioArctic. LEQEMBI is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). In the U.S., LEQEMBI was granted accelerated approval by the U.S. Food and Drug Administration (FDA) on January 6, 2023. LEQEMBI is indicated for the treatment of Alzheimer’s disease (AD) in the U.S. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. This indication is approved under accelerated approval based on reduction in Aβ plaques observed in patients treated with LEQEMBI. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.
In the U.S., Eisai submitted a supplemental Biologics License Application (sBLA) to the FDA for approval under the traditional pathway on January 6, 2023. On March 3, 2023, the FDA accepted Eisai’s sBLA based on the Clarity AD clinical data, and the LEQEMBI application has been granted Priority Review, with a Prescription Drug User Fee Act (PDUFA) action date of July 6, 2023. The Clarity AD study of lecanemab met its primary endpoint and all key secondary endpoints with highly statistically significant results. Eisai submitted an application for manufacturing and marketing approval to the Pharmaceuticals and Medical Devices Agency (PMDA) on January 16, 2023, in Japan. The Priority Review was granted by the Ministry of Health, Labour and Welfare (MHLW) on January 26, 2023. Eisai utilized the prior assessment consultation system of PMDA, with the aim of shortening the review period for lecanemab. In Europe, Eisai submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) on January 9, 2023, and accepted on January 26, 2023. In China, Eisai initiated submission of data for a BLA to the National Medical Products Administration (NMPA) of China in December 2022, and the Priority Review was granted on February 27, 2023.
Eisai has completed lecanemab subcutaneous bioavailability study, and subcutaneous dosing is currently being evaluated in the Clarity AD OLE.
Since July 2020, Eisai’s Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains, is ongoing. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer’s Clinical Trial Consortium (ACTC) that provides the infrastructure for academic clinical trials in AD and related dementias in the U.S., funded by the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen. The Tau NexGen clinical study for Dominantly Inherited AD (DIAD), that is conducted by Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, has been ongoing since January 2022.
About the Collaboration between Eisai and Biogen for AD
Eisai and Biogen have been collaborating on the joint development and commercialization of AD treatments since 2014. Eisai serves as the lead of lecanemab development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.
About the Collaboration between Eisai and BioArctic for AD
Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development and commercialization of AD treatments. Eisai obtained the global rights to study, develop, manufacture and market LEQEMBI for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercialization agreement on the antibody LEQEMBI back-up was signed in May 2015.
References
1 Söderberg, L., Johannesson, M., Nygren, P. et al. Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer’s Disease. Neurotherapeutics (2022). https://doi.org/10.1007/s13311-022-01308-6. Accessed February 9, 2023
by codm | Mar 10, 2023 | Newsletter
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Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it was selected as the winner of the “Basic Achievement Grand Prize” at the “2023 J-Win Diversity Award” held by non-profit organization Japan Women’s Innovative Network (NPO J-Win).
The “J-Win Diversity Award” has been held annually since 2008 with the aim of accelerating the promotion of diversity and inclusion (D&I) in Japanese companies by awarding leading businesses that are promoting D&I. Among the Company Prizes, Eisai was selected as the winner of the “Basic Achievement Grand Prize”, which is the highest award within the “Basic Category” covering businesses who demonstrate the significance and purpose of female empowerment, developing systems and frameworks with set goals, and are taking action as a first step towards D&I promotion.
● Reasons For Award-Winner Selection
Promoting D&I by viewing acquisition of diverse human talents and their successes as essential for realizing their corporate concept. While promoting company-wide initatives with the “DE&I (Diversity, Equity & Inclusion) Promotion Committee”, encouraging independent activities appropriate to onsite challenges through “DE&I projects” at each department. Further expansion in the number of female managers is expected down the road.
● Highly Regarded Measures/Initiatives
1) Top management commitment and promotional framework for D&I
・Promoting D&I by regarding acquisition and retention of diverse human talents and their successes as essential to evolve the “hhc (human health care)” concept and realize an “hhceco company”
・Promoting activities by division, setting up “DE&I Projects” for global functions, such as corporate, R&D and manufacturing operations as well as each regional function, in parallel with implementing the ”DE&I Promotion Committee” throughout the company.
・Plans to introduce a new personnel assessment system from FY 2023, which utilizes a behavioral assessment item “Diversity & Synergy” to further focus on diversity.
2) Developing female leaders
・Implementing E-Win (Eisai Women’s Innovative Network) program to encourage personal growth and foster career awareness/aspirations
3) Reforming corporate culture/promoting increased awareness
・Promoting dialogues within the organization by leveraging monthly engagement survey
Eisai’s corporate concept (also known as the hhc Concept) is to give first thought to patients and the people in the daily living domain, and increase the benefits that healthcare provides to them as well as meet their diversified healthcare needs worldwide. Eisai aims to realize the spiral of knowledge generated by diversity, regardless of differences in nationality, gender, age, etc., leading to the creation of innovation. Eisai also acquired third party appraisals including “Platinum Kurumin”, an accreditation for organizations implementing high level parenting support by Ministry of Health, Labour and Welfare, as well as “the New Diversity Management Selection 100” and “Health & Productivity Management Outstanding Organizations” by Ministry of Economy, Trade and Industry.
Eisai is promoting DE&I throughout the company to ensure it has the diversity to meet increasingly diverse needs of patients and the people in the daily living domain.
For more information about Eisai’s DE&I promotion, please visit it’s corporate website.
Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120
by codm | Mar 9, 2023 | Newsletter
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Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it has been certified as a Health and Productivity Management Outstanding Organization in the large enterprise category (White 500) by Japan’s Ministry of Economy, Trade and Industry and the Nippon Kenko Kaigi.
Under the Certified Health and Productivity Management Outstanding Organization Recognition Program, the Nippon Kenko Kaigi examines large enterprises, small and medium enterprises and other organizations engaging in initiatives for overcoming health-related challenges in regional communities or for promoting health-conscious activities led by the Nippon Kenko Kaigi. It recognizes outstanding enterprises engaging in efforts for health and productivity management by evaluating from a business-management perspective based on the following criteria: “management philosophy and policies”, “organized frameworks”, “systems and implementation of measures”, and “evaluation and improvement”. Eisai exceeded the average of its industry peers in all criteria, receiving particularly high scores for items such as “well adopted by employees” (in the criteria of organized frameworks), “lifestyle improvement” and “other measures*” (in the criteria of systems and implementation of measures). The program was launched in 2017, and this is the fifth time that Eisai was certified as a “White 500” company.
Eisai’s corporate concept is to give first thought to patients and the people in the daily living domain, and increase the benefits that health care provides to them as well as meet their diversified healthcare needs worldwide. Eisai calls this the “human health care (hhc)” concept. Eisai regards its employees as an important stakeholder and asset for the realization of its hhc concept. Eisai believes that its commitment to maintaining and improving the health of human resources is fundamental to develop highly engaged employees who are motivated to contribute voluntarily toward the realization of the hhc concept. Eisai issued the “Eisai Health Declaration” in 2019, and has strategically implemented health management for employees from a management perspective.
Eisai will continue to promote health and productivity management to increase non-financial value and further contribute to increasing the benefits of patients and the people in the daily living domain.
* Measures to address health issues specific to women and the elderly, long working hours, mental health, dependents of the company’s employees, and prevention of infectious disease during COVID-19 pandemic.
Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120
by codm | Mar 6, 2023 | Newsletter
Confirmatory Phase 3 Clarity AD data to be evaluated by FDA in determining whether to convert accelerated approval of LEQEMBI to a traditional approval
Priority Review accelerates FDA review time with a Prescription Drug User Fee Act (PDUFA) target action on July 6, 2023
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TOKYO and CAMBRIDGE, Mass., March 6, 2023 – Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Christopher A. Viehbacher, “Biogen”) announced today that the U.S. Food and Drug Administration (FDA) has accepted Eisai’s supplemental Biologics License Application (sBLA) for LEQEMBI™ (lecanemab-irmb) 100 mg/mL injection for intravenous use, supporting the conversion of the accelerated approval of LEQEMBI to a traditional approval. The LEQEMBI application has been granted Priority Review, with a Prescription Drug User Fee Act (PDUFA) action date of July 6, 2023. The FDA is currently planning to hold an Advisory Committee to discuss this application but has not yet publicly announced the date of the meeting.
LEQEMBI is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibrils*) and insoluble forms of amyloid beta (Aβ), approved under the Accelerated Approval Pathway for the treatment of Alzheimer’s Disease (AD) on January 6, 2023. Treatment with LEQEMBI should only be initiated in patients with the mild cognitive impairment or mild dementia stage of disease and confirmed presence of Aβ pathology. On the same day that LEQEMBI received its accelerated approval, Eisai submitted the sBLA to the FDA for approval under the traditional pathway.
The sBLA is based on the findings from Eisai’s recently published large, global confirmatory Phase 3 clinical trial, Clarity AD. LEQEMBI met the primary endpoint and all key secondary endpoints with highly statistically significant results. In November 2022, results of the Clarity AD study were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference and simultaneously published in the peer-reviewed medical journal, The New England Journal of Medicine.
LEQEMBI was approved under accelerated approval in the U.S. and was launched in the U.S. on January 18, 2023. The accelerated approval was based on Phase 2 data that demonstrated that LEQEMBI reduced the accumulation of Aβ plaque in the brain, a defining feature of AD, and its continued approval may be contingent upon verification of LEQEMBI’s clinical benefit in a confirmatory trial. The FDA has determined that the results of Clarity AD can serve as the confirmatory study to verify the clinical benefit of lecanemab.
Eisai serves as the lead of LEQEMBI development and regulatory submissions globally with both Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority.
* Protofibrils are large Aβ aggregated soluble species of 75-500 Kd. 1
To learn more, visit www.LEQEMBI.com.
INDICATION, DOSAGE AND ADMINISTRATION, AND IMPORTANT SAFETY INFORMATION IN THE U.S.
INDICATION
LEQEMBI is indicated for the treatment of Alzheimer’s disease. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. This indication is approved under accelerated approval based on reduction in amyloid beta plaques observed in patients treated with LEQEMBI. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Amyloid Related Imaging Abnormalities
- LEQEMBI can cause amyloid related imaging abnormalities-edema (ARIA-E) and -hemosiderin deposition (ARIA-H). ARIA-E can be observed on MRI as brain edema or sulcal effusions, and ARIA-H as microhemorrhage and superficial siderosis. ARIA is usually asymptomatic, although serious and life threatening events, including seizure and status epilepticus, rarely can occur. Reported symptoms associated with ARIA may include headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms associated with ARIA usually resolve over time.
ARIA Monitoring and Dose Management Guidelines
- Obtain recent (within one year) brain magnetic resonance imaging (MRI) prior to initiating treatment with LEQEMBI. Obtain an MRI prior to the 5th, 7th, and 14th infusions.
- Recommendations for dosing in patients with ARIA-E and ARIA-H depend on clinical symptoms and radiographic severity. Depending on ARIA severity, use clinical judgment in considering whether to continue dosing, temporarily discontinue treatment, or permanently discontinue LEQEMBI.
- Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment with LEQEMBI. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including MRI if indicated. If ARIA is observed on MRI, careful clinical evaluation should be performed prior to continuing treatment.
- There is no experience in patients who continued dosing through symptomatic ARIA-E or through asymptomatic, but radiographically severe, ARIA-E. There is limited experience in patients who continued dosing through asymptomatic but radiographically mild to moderate ARIA-E. There are limited data in dosing patients who experienced recurrent ARIA-E.
Incidence of ARIA
- In Study 1 (Study 201), symptomatic ARIA occurred in 3% (5/161) of LEQEMBI-treated patients. Clinical symptoms associated with ARIA resolved in 80% of patients during the period of observation.
- Including asymptomatic cases, ARIA was observed in LEQEMBI: 12% (20/161); placebo: 5% (13/245). ARIA-E was observed in LEQEMBI: 10% (16/161); placebo: 1% (2/245). ARIA-H was observed in LEQEMBI: 6% (10/161); placebo: 5% (12/245). There was no increase in isolated ARIA-H for LEQEMBI compared to placebo.
- Intracerebral hemorrhage >1 cm in diameter was reported after one treatment in LEQEMBI: 1 patient; placebo: zero patients. Events of intracerebral hemorrhage, including fatal events, in patients taking LEQEMBI have also been reported in other studies.
Apolipoprotein E ε4 (ApoE ε4) Carrier Status and Risk of ARIA
- In Study 1, 6% (10/161) of patients in the LEQEMBI group were ApoE ε4 homozygotes, 24% (39/161) were heterozygotes, and 70% (112/161) were noncarriers.
- The incidence of ARIA was higher in ApoE ε4 homozygotes than in heterozygotes and noncarriers among patients treated with LEQEMBI. Of the 5 LEQEMBI-treated patients who had symptomatic ARIA, 4 were ApoE ε4 homozygotes, 2 of whom experienced severe symptoms. An increased incidence of symptomatic and overall ARIA in ApoE ε4 homozygotes compared to heterozygotes and noncarriers in LEQEMBI-treated patients has been reported in other studies.
- The recommendations on management of ARIA do not differ between ApoE ε4 carriers and noncarriers.
- Consider testing for ApoE ε4 status to inform the risk of developing ARIA when deciding to initiate treatment with LEQEMBI.
Radiographic Findings
- The majority of ARIA-E radiographic events occurred early in treatment (within the first 7 doses), although ARIA can occur at any time and patients can have more than 1 episode. The maximum radiographic severity of ARIA-E in patients treated with LEQEMBI was mild in 4% (7/161) of patients, moderate in 4% (7/161) of patients, and severe in 1% (2/161) of patients. Resolution on MRI occurred in 62% of ARIA-E patients by 12 weeks, 81% by 21 weeks, and 94% overall after detection. The maximum radiographic severity of ARIA-H microhemorrhage in patients treated with LEQEMBI was mild in 4% (7/161) of patients and severe in 1% (2/161) of patients; 1 of the 10 patients with ARIA-H had mild superficial siderosis.
Concomitant Antithrombotic Medication and Other Risk Factors for Intracerebral Hemorrhage
- Patients were excluded from enrollment in Study 1 for baseline use of anticoagulant medications. Antiplatelet medications such as aspirin and clopidogrel were allowed. If anticoagulant medication was used because of intercurrent medical events that required treatment for ≤4 weeks, treatment with LEQEMBI was to be temporarily suspended.
- Most exposures to antithrombotic medications were to aspirin; few patients were exposed to other antiplatelet drugs or anticoagulants, limiting any meaningful conclusions about the risk of ARIA or intracerebral hemorrhage in patients taking other antiplatelet drugs or anticoagulants. Because intracerebral hemorrhages >1 cm in diameter have been observed in patients taking LEQEMBI, additional caution should be exercised when considering the administration of antithrombotics or a thrombolytic agent (e.g., tissue plasminogen activator) to a patient already being treated with LEQEMBI.
- Patients were excluded from enrollment in Study 1 for the following risk factors for intracerebral hemorrhage: prior cerebral hemorrhage >1 cm in greatest diameter, more than 4 microhemorrhages, superficial siderosis, evidence of vasogenic edema, evidence of cerebral contusion, aneurysm, vascular malformation, infective lesions, multiple lacunar infarcts or stroke involving a major vascular territory, and severe small vessel or white matter disease. Caution should be exercised when considering the use of LEQEMBI in patients with these risk factors.
Infusion-Related Reactions
- Infusion-related reactions were observed in LEQEMBI: 20% (32/161); placebo: 3% (8/245), and the majority of cases in LEQEMBI-treated patients (88%, 28/32) occurred with the first infusion. All infusion related reactions were mild (56%) or moderate (44%) in severity. Infusion-related reactions resulted in discontinuations in 2% (4/161) of patients treated with LEQEMBI. Symptoms of infusion-related reactions included fever and flu-like symptoms (chills, generalized aches, feeling shaky, and joint pain), nausea, vomiting, hypotension, hypertension, and oxygen desaturation.
- After the first infusion, 38% of LEQEMBI-treated patients had transient decreased lymphocyte counts to <0.9 x109/L compared to 2% on placebo, and 22% of LEQEMBI-treated patients had transient increased neutrophil counts to >7.9 x109/L compared to 1% on placebo.
- In the event of an infusion-related reaction, the infusion rate may be reduced, or the infusion may be discontinued, and appropriate therapy initiated as clinically indicated. Prophylactic treatment with antihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids prior to future infusions may be considered.
ADVERSE REACTIONS
- In Study 1, 15% of LEQEMBI-treated patients, compared to 6% of placebo-treated patients, stopped study treatment because of an adverse reaction. The most common adverse reaction leading to discontinuation of LEQEMBI was infusion-related reactions that led to discontinuation in 2% (4/161) of patients treated with LEQEMBI compared to 1% (2/245) of patients on placebo.
- The most common adverse reactions reported in ≥5% of patients treated with LEQEMBI (N=161) and ≥2% higher than placebo (N=245) in Study 1 were infusion-related reactions (LEQEMBI: 20%; placebo: 3%), headache (LEQEMBI: 14%; placebo: 10%), ARIA-E (LEQEMBI: 10%; placebo: 1%), cough (LEQEMBI: 9%; placebo: 5%), and diarrhea (LEQEMBI: 8%; placebo: 5%).
Please see full Prescribing Information
Media Contacts:
| Eisai |
Biogen Inc. |
|
Eisai Co., Ltd.
Public Relations Department
Eisai Inc. (U.S.)
Libby Holman
Eisai Europe, Ltd.
(Europe, Australia, New Zealand and Russia)
EMEA Communications Department
|
Natacha Gassenbach
+ 1-857-777-6573
public.affairs@biogen.com |
Investor Contacts:
| Eisai Co., Ltd. |
Biogen Inc. |
Investor Relations Department
|
Mike Hencke
|
[Notes to Editors]
1. About LEQEMBITM (lecanemab-irmb)
LEQEMBITM (lecanemab-irmb) is the result of a strategic research alliance between Eisai and BioArctic. LEQEMBI is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). In the U.S., LEQEMBI was granted accelerated approval by the U.S. Food and Drug Administration (FDA) on January 6, 2023. LEQEMBI is indicated for the treatment of Alzheimer’s disease (AD) in the U.S. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. This indication is approved under accelerated approval based on reduction in Aβ plaques observed in patients treated with LEQEMBI. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.
In the U.S., Eisai submitted a supplemental Biologics License Application (sBLA) to the FDA for approval under the traditional pathway on January 6, 2023. The Clarity AD study of lecanemab met its primary endpoint and all key secondary endpoints with highly statistically significant results. Eisai submitted an application for manufacturing and marketing approval to the Pharmaceuticals and Medical Devices Agency (PMDA) on January 16, 2023, in Japan. The Priority Review was granted by the Ministry of Health, Labour and Welfare (MHLW) on January 26, 2023. Eisai utilized the prior assessment consultation system of PMDA, with the aim of shortening the review period for lecanemab. In Europe, Eisai submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) on January 9, 2023, and accepted on January 26, 2023. In China, Eisai initiated submission of data for a BLA to the National Medical Products Administration (NMPA) of China in December 2022, and the Priority Review was granted on February 27, 2023.
Eisai has completed lecanemab subcutaneous bioavailability study, and subcutaneous dosing is currently being evaluated in the Clarity AD OLE.
Since July 2020, Eisai’s Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains, is ongoing. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer’s Clinical Trial Consortium (ACTC) that provides the infrastructure for academic clinical trials in AD and related dementias in the U.S., funded by the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen. The Tau NexGen clinical study for Dominantly Inherited AD (DIAD), that is conducted by Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, has been ongoing since January 2022.
2. About the Collaboration between Eisai and Biogen for AD
Eisai and Biogen have been collaborating on the joint development and commercialization of AD treatments since 2014. Eisai serves as the lead of lecanemab development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.
3. About the Collaboration between Eisai and BioArctic for AD
Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development and commercialization of AD treatments. Eisai obtained the global rights to study, develop, manufacture and market LEQEMBI for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercialization agreement on the antibody LEQEMBI back-up was signed in May 2015.
4. About Eisai Co., Ltd.
Eisai’s Corporate Concept is “to give first thought to patients and people in the daily living domain, and to increase the benefits that health care provides.” Under this concept (also known as the human health care [hhc] concept), we aim to effectively achieve social good in the form of relieving anxiety over health and reducing health disparities. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to create and deliver innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of neurology and oncology.
In addition, we demonstrate our commitment to the elimination of neglected tropical diseases (NTDs), which is a target (3.3) of the United Nations Sustainable Development Goals (SDGs), by working on various activities together with global partners.
For more information about Eisai, please visit www.eisai.com (for global headquarters: Eisai Co., Ltd.), and connect with us on Twitter @Eisai_SDGs.
5. About Biogen
Founded in 1978, Biogen is a leading global biotechnology company that has pioneered multiple breakthrough innovations including a broad portfolio of medicines to treat multiple sclerosis, the first approved treatment for spinal muscular atrophy, and two co-developed treatments to address a defining pathology of Alzheimer’s disease. Biogen is advancing a pipeline of potential novel therapies across neurology, neuropsychiatry, specialized immunology and rare diseases and remains acutely focused on its purpose of serving humanity through science while advancing a healthier, more sustainable and equitable world.
The company routinely posts information that may be important to investors on its website at www.biogen.com. Follow Biogen on social media – Twitter, LinkedIn, Facebook, YouTube.
Biogen Safe Harbor
This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, about the potential clinical effects of lecanemab; the potential benefits, safety and efficacy of lecanemab; potential regulatory discussions, submissions and approvals and the timing thereof; the treatment of Alzheimer’s disease; the anticipated benefits and potential of Biogen’s collaboration arrangements with Eisai; the potential of Biogen’s commercial business and pipeline programs, including lecanemab; and risks and uncertainties associated with drug development and commercialization. These statements may be identified by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “intend,” “may,” “plan,” “possible,”” “potential,” “will,” “would” and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical studies may not be indicative of full results or results from later stage or larger scale clinical studies and do not ensure regulatory approval. You should not place undue reliance on these statements or the scientific data presented.
These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation unexpected concerns that may arise from additional data, analysis or results obtained during clinical studies, including the Clarity AD clinical trial and AHEAD 3-45 study; the occurrence of adverse safety events; risks of unexpected costs or delays; the risk of other unexpected hurdles; regulatory submissions may take longer or be more difficult to complete than expected; regulatory authorities may require additional information or further studies, or may fail or refuse to approve or may delay approval of Biogen’s drug candidates, including lecanemab; actual timing and content of submissions to and decisions made by the regulatory authorities regarding lecanemab; uncertainty of success in the development and potential commercialization of lecanemab; failure to protect and enforce Biogen’s data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; product liability claims; third party collaboration risks; and the direct and indirect impacts of the ongoing COVID-19 pandemic on Biogen’s business, results of operations and financial condition. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from Biogen’s expectations in any forward-looking statement. Investors should consider this cautionary statement as well as the risk factors identified in Biogen’s most recent annual or quarterly report and in other reports Biogen has filed with the U.S. Securities and Exchange Commission. These statements are based on Biogen’s current beliefs and expectations and speak only as of the date of this news release. Biogen does not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.
References
1 Söderberg, L., Johannesson, M., Nygren, P. et al. Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer’s Disease. Neurotherapeutics (2022). https://doi.org/10.1007/s13311-022-01308-6. Accessed February 9, 2023
