Latest findings from Eisai's robust
Alzheimer's disease (AD) pipeline will be shared, including the
importance of continued treatment of AD, which is a progressive
neurodegenerative disease that begins before plaque deposition and
continues after plaque removal
TOKYO, July 22,
2024 /PRNewswire/ -- Eisai Co. Ltd (Headquarters:
Tokyo, CEO: Haruo Naito, "Eisai") announced today that the
company will present the latest findings on its Alzheimer's disease
(AD) pipeline and research, including our dual-acting, anti-amyloid
beta (Aβ) protofibril* antibody for the treatment of AD, lecanemab
(generic name, U.S. brand name: LEQEMBI®), at the
Alzheimer's Association International Conference (AAIC).
Dual-acting lecanemab is the only early AD treatment available to
support neuronal function by clearing the highly toxic protofibrils
that continue to cause neuronal injury and death even after plaques
have been cleared from the brain. The conference will be held in
Philadelphia and virtually from
July 28 to August 1, 2024. Eisai will
present data and research in four (4) oral and 15 poster
presentations at the meeting and will host two (2) sessions on
lecanemab.
![Eisai logo (PRNewsfoto/Eisai Inc.) Eisai logo (PRNewsfoto/Eisai Inc.)](https://mma.prnewswire.com/media/2348748/Eisai_logo_svg_Logo.jpg)
Perspectives Session: Does the Current Evidence Base Support
Lecanemab Continued Dosing for Early Alzheimer's Disease?
- On July 30 from 4:15 p.m. to 5:45 p.m. EDT, Eisai will present
the latest data exploring three critical topics:
- Does the current evidence for lecanemab mechanism support a
rationale for continued lecanemab dosing?
- Is the lecanemab maintenance dosing regimen supported by
simulation models?
- Is there evidence for a continued benefit for long-term
lecanemab treatment?
- Dennis Selkoe, M.D., will focus on the toxicity of soluble
aggregated amyloid-beta species, including oligomers, protofibrils
and diffusible fibrils. The session will review the latest data on
the mechanism of action of lecanemab, which binds to protofibrils
and oligomers that continue to be produced even after plaques are
cleared. Additional discussion will focus on the potential
mechanistic justification for ongoing treatment to maintain
clinical and biomarker efficacy.
- Data from an intervening off-treatment period (gap period)
occurring after the completion of the core phase of the Phase II
Study 201 and before the initiation of the open-label extension
(OLE) suggested the importance of continued administration of
lecanemab. Youfang Cao, PhD., and
Larisa Reyderman, Ph,D., from Eisai
will present clinical pharmacology data and clinical pharmacology
modeling outcomes that combine the outcomes from Study 201 and the
Phase 3 Clarity AD study, which will provide insights into
potential lecanemab maintenance dosing.
- Christopher van Dyck, M.D., will present the latest
36-month efficacy and safety data from dual-acting lecanemab's
Phase 3 Clarity AD core and OLE studies and panelists will discuss
the potential benefits of continuous treatment of AD, which is a
progressive, neurodegenerative disease that begins before plaque
deposition and continues after plaque removal.
Featured Research Session: Beyond Amyloid Removal with
Lecanemab Treatment: Update on Long-Term Imaging and Fluid
Biomarkers.
- In this Featured Research session on July 30 from 2:00 PM to
3:30 PM EDT, the latest findings on imaging and fluid
biomarkers from dual-acting lecanemab treatment will be
presented.
- Brian Willis, PhD., and Arnaud
Charil, PhD of Eisai will present the outcomes of recent PK/PD
modeling examining the potential connection between dual-acting
lecanemab's PK and amyloid PET, CDR-SB, and the outcomes of the tau
PET from Carity AD core and OLE studies.
- Nick Fox, M.D., FRCP, FMedSci,
will explain the changes in brain volume that occur with
anti-amyloid immunotherapy and its potential relationship to
amyloid clearance.
- Charlotte Teunissen, PhD., will
present data on neurodegenerative biomarkers in plasma as a result
of long-term treatment of dual-acting lecanemab, and will also
explain the necessity for maintenance treatment from these changes
in biomarkers.
"At AAIC 2024, Eisai will present the results from the Phase 2
and Phase 3 lecanemab studies and open label extensions exploring
ongoing dosing with dual-acting lecanemab for potential longer-term
clinical and biomarker benefit," said Michael Irizarry, M.D., Deputy Chief Clinical
Officer and Senior Vice President of Clinical Research at Eisai
Inc. "Alzheimer's disease (AD) is a progressive and relentless
disease caused by a continuous underlying neurotoxic process. There
is an urgency to treat because early and ongoing treatment can slow
the progression of Alzheimer's disease. The earlier mild cognitive
impairment (MCI) due to AD and mild AD dementia are diagnosed and
treated, the greater the opportunity for the patient to
benefit."
Key Presentation
■ Perspectives Session:
Does the Current Evidence Base Support Lecanemab Continued
Dosing for Early Alzheimer's Disease? From 4:15 PM to 5:45 PM EDT on July 30, 2024
Session Program
Does the Current Evidence for Lecanemab Mechanism Support a
Rationale for Continued Lecanemab Dosing?
How Does the Latest Clinical Pharmacology Data & Modeling
Support Continued Lecanemab Dosing?
Neuro-Dynamic Quantitative Systems Pharmacology (QSP) Model
Supports Continued Lecanemab Treatment With Maintenance Dosing For
Alzheimer's Disease
Is there Evidence for a Continued Benefit for Long-Term
Lecanemab Treatment? A Benefit/Risk Update from Long-Term Efficacy,
Safety and Biomarker Data
Q&A
■ Featured Research Session
Beyond Amyloid Removal with Lecanemab Treatment: Update on
Long-Term Imaging and Fluid Biomarkers From 2:00 PM to 3:30 PM EDT on July 30, 2024
Session Program
Amyloid Plaque Reduction as a Biomarker of Efficacy: Assessment
of Amyloid PET and Change in CDR-SB Utilizing Semi-Mechanistic
Model
Lecanemab Slows Tau PET Accumulation
"Paradoxical" Cerebral Volume Changes in Anti-Amyloid
Immunotherapy Trials
Long-Term Effects of Lecanemab on Biomarkers of
Neurodegeneration in Plasma
Q&A
■ Oral Presentations
Asset/Project,
Presentation Date and Time (EDT, U.S)
|
Topic, Abstract
number
|
|
|
Lecanemab
July 30 (Tue) 2:42 PM – 2:49 PM
|
Examining
Lecanemab-Associated Amyloid-Beta Protofibril as a Proximal
Biomarker of Neurodegeneration Unlike Other Plaque-Associated
Biomarkers
Abstract ID
#94585
|
|
|
Lecanemab
July 30 (Tue) 2:49 PM – 2:56 PM
|
Lecanemab,
Amyloid-Induced Tau Pathology as Supported CSF MTBR-tau243 in
Clarity AD
Abstract ID
#95507
|
|
|
E2027
July 31 (Wed) 5:05 PM – 5:15 PM
|
The Effects of the
Novel Phosphodiesterase 9 (pde9) Inhibitor E2027 (irsenontrine) on
CSF Proteomics Profile in Amyloid Positive and Amyloid Negative
Lewy Body Dementia
Abstract ID
#91293
|
|
|
General AD
July 29 (Mon) 8:00 AM – 8:10 AM
|
Unmet Needs in the
Diagnosis and Management of Early AD in Community-Based Settings in
the United States
Abstract ID
#89135
|
■ Poster Presentations
Asset/Project,
Presentation Date and Time (EDT, U.S)
|
Topic, Abstract
number
|
|
|
Lecanemab
July 28 (Sun)
|
Model-Based Assessment
of Lecanemab Maintenance Dosing Regimen and Potential for Continued
Suppression of Amyloid Plaque, Disease Progression
Abstract ID #89308
|
|
|
E2814
July 30
(Tue)
|
Crystal Structure of
E2814 Bound to Tau
Abstract ID
#94773
|
|
|
E2511 July 28
(Sun)
|
Non-Clinical Evidence
for Modulating Synaptic CSF Biomarkers by E2511: A Novel Small
Compound TrkA Biased Positive Allosteric Modulator
Abstract ID #95071
|
|
|
E2025
July 28
(Sun)
|
E2025, A Novel
Anti-EphA4 Antibody, Enhances EphA4 Cleavage, and Suppresses Tau
Pathologies in a Transgenic Model of AD
Abstract ID
#94810
|
|
|
Biomarker
July 29 (Mon)
|
Prediction of Regional
Brain Tau Levels in Early Alzheimer's Disease Using Plasma
pTau217
Abstract ID #95793
|
|
|
Biomarker
July 31 (Wed)
|
A Prospective
Multi-Clinic Implementation Science Study to Evaluate Use of Blood-
Based Biomarkers as Confirmatory Diagnostic Tools for Early
Alzheimer's Disease in Real-World Clinical Practice
Abstract ID #88784
|
|
|
Biomarkers
July 30 (Tue)
|
Advancing Early
Detection of Alzheimer's Disease in the Primary Care Setting in the
United States
Abstract ID #86582
|
|
|
Imaging
July 31 (Wed)
|
Volumes of Specific
Substrates Within the Amygdala and Hippocampus are Impacted by
Brain Amyloid-β
Abstract ID
#92024
|
|
|
General AD
July 28 (Sun)
|
Total Healthcare Costs
Across the Alzheimer's Disease Continuum in the United States
(US)
Abstract ID #86386
|
|
|
General AD
July 29 (Mon)
|
Risk Factors for Mild
Cognitive Impairment: Prediction Models Developed with Electronic
Health Record Data
Abstract ID
#85564
|
|
|
General AD
July 29 (Mon)
|
Patterns in the
Diagnosis and Management of Early AD in Community-Based Settings in
the United States
Abstract ID #92630
|
|
|
General AD
July 30 (Tue)
|
Usage Patterns of
Anticoagulant Therapy in Patients with Mild Cognitive Impairment or
Alzheimer's Disease
Abstract ID #86110
|
|
|
General AD
July 30 (Tue)
|
Adapting Healthcare
Infrastructure for Disease-Modification in Early Alzheimer's
Disease
Abstract ID
#94773
|
|
|
General AD
July 31 (Wed)
|
Critical Path for
Alzheimer's Disease (CPAD) Consortium: Data-Driven Solutions for
Clinical Trial Design and Informed Decision Making
Abstract ID
#86145
|
|
|
General AD
July 29 (Mon)
|
Expectations and
Perspectives of Patients and Physicians on New Treatment for Early
Alzheimer's Disease: Results of a Physician Survey and Patient
Focus Group Interview
Abstract ID
#86956
|
Poster viewing time is set from 3:30PM to
4:15PM, during break and lunch time on the date of
presentation.
This release discusses investigational uses of agents in
development and is not intended to convey conclusions about
efficacy or safety. There is no guarantee that such investigational
agents will successfully complete clinical development or gain
health authority approval.
* Protofibrils are believed to contribute to the brain injury
that occurs with AD and are considered to be the most toxic form of
Aβ, having a primary role in the cognitive decline associated with
this progressive, debilitating condition.1 Protofibrils cause
injury to neurons in the brain, which in turn, can negatively
impact cognitive function via multiple mechanisms, not only
increasing the development of insoluble Aβ plaques but also
increasing direct damage to brain cell membranes and the
connections that transmit signals between nerve cells or nerve
cells and other cells. It is believed the reduction of protofibrils
may prevent the progression of AD by reducing damage to neurons in
the brain and cognitive dysfunction.2
Media Inquiries:
Eisai Co., Ltd.
Public Relations Department
TEL: +81 (0)3-3817-5120
Eisai Inc. (U.S.)
Libby Holman
+1-201-753-1945
Libby_Holman@Eisai.com
Eisai Europe, Ltd. (UK, Europe,
Australia, New Zealand and Russia)
EMEA Communications Department
+44 (0) 786 601 1272
EMEA-comms@eisai.net
[Notes to editors]
- About Lecanemab
(LEQEMBI®),
Lecanemab is the result
of a strategic research alliance between Eisai and BioArctic. It is
a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody
directed against aggregated soluble (protofibril) and insoluble
forms of amyloid-beta (Aβ). Lecanemab is approved in the U.S.,
Japan, China, South
Korea, Hong Kong and
Israel. Eisai has also submitted
applications for approval of lecanemab in 12 countries and regions,
including the European Union (EU).
LEQEMBI's FDA approval was based on Phase 3 data from Eisai's,
global Clarity AD clinical trial, in which it met its primary
endpoint and all key secondary endpoints with statistically
significant results. The primary endpoint was the global cognitive
and functional scale, Clinical Dementia Rating Sum of Boxes
(CDR-SB). In the Clarity AD clinical trial, treatment with
lecanemab reduced clinical decline on CDR-SB by 27% at 18 months
compared to placebo.3,4 The mean CDR-SB score at
baseline was approximately 3.2 in both groups. The adjusted
least-squares mean change from baseline at 18 months was 1.21 with
lecanemab and 1.66 with placebo (difference, −0.45; 95% confidence
interval [CI], −0.67 to −0.23; P<0.001). In addition, the
secondary endpoint from the AD Cooperative Study-Activities of
Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL),
which measures information provided by people caring for patients
with AD, noted a statistically significant benefit of 37% compared
to placebo. The adjusted mean change from baseline at 18 months in
the ADCS-MCI-ADL score was −3.5 in the lecanemab group and −5.5 in
the placebo group (difference, 2.0; 95% CI, 1.2 to 2.8;
P<0.001). The ADCS MCI-ADL assesses the ability of patients to
function independently, including being able to dress, feed
themselves and participate in community activities. The most common
adverse events (>10%) in the lecanemab group were infusion
reactions, ARIA-H (combined cerebral microhemorrhages, cerebral
macrohemorrhages, and superficial siderosis), ARIA-E
(edema/effusion), headache, and fall.
In November 2023, Eisai presented
24-month data from the Phase 3 Clarity AD open Label Extension
Study demonstrating that LEQEMBI-treated patients continued to show
benefit at 24 months of treatment. In the 18-month core study of
Clarity AD, there was a statistically significant difference in
global cognition and function as measured by CDR-SB between the
LEQEMBI and placebo groups. The separation in CDR-SB between the
group that continued to receive LEQEMBI (early start group) and the
group who switched from placebo to LEQEMBI (delayed start group)
was maintained during the 6-month OLE following the core study.
This indicates that similar disease trajectory for both early and
delayed start groups occurred with LEQEMBI administration. The
blood biomarker results (plasma Aβ42/40 ratio, ptau181, GFAP and
NfL) showed improvement even after delayed initiation of treatment
with LEQEMBI.
These results suggest that LEQEMBI treatment may affect clinical
outcomes through improvement of AD pathology. 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 and includes lecanemab as the backbone anti-amyloid
therapy.
- About E2814
An investigational anti-microtubule
binding region (MTBR) tau antibody, E2814, is being developed as a
disease-modifying agent for tauopathies including sporadic AD.
Phase I clinical studies are underway. E2814 was discovered as part
of the research collaboration between Eisai and University College
London. E2814 is designed to prevent the spreading of tau seeds
within the brains of affected individuals. In addition, a Phase
II/III Tau NexGen study for the treatment of dominantly inherited
Alzheimer's disease (DIAD), conducted by the Dominantly Inherited
Alzheimer Network Trials Unit (DIAN-TU) led by Washington University School of Medicine in
St. Louis (St. Louis, MO, USA), is underway.
- About E2511
E2511 is Eisai's in-house discovered and
developed investigational novel molecule that directly binds to
tropomyosin receptor kinase A (TrkA); a nerve growth factor (NGF)
located on the neural cell membrane. E2511 could potentially
promote recovery and synaptic remodeling of damaged cholinergic
neurons. A Phase 1 study for E2511 is underway.
- About E2025
E2025 is Eisai's in-house discovered and
developed investigational novel anti-EphA4
(Erythropoietin-producing hepatocellular receptor A4) antibody that
enhances EphA4 cleavage. E2025 could potentially promote synaptic
remodeling of glutamic neurons. A Phase 1 study for E2025 is
underway.
- About the Collaboration between Eisai and Biogen for
Alzheimer's Disease
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 Eisai and Biogen
co-commercializing and co-promoting the product and Eisai having
final decision-making authority.
- About the Collaboration between Eisai and BioArctic for
Alzheimer's Disease
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 back-up was
signed in May 2015.
References
- Amin L, Harris DA. Aβ receptors specifically recognize
molecular features displayed by fibril ends and neurotoxic
oligomers. Nat Commun.
2021;12:3451. doi:10.1038/s41467-021-23507-z
- Ono K, Tsuji M. Protofibrils of Amyloid-β are Important Targets
of a Disease-Modifying Approach for Alzheimer's Disease. Int J
Mol Sci. 2020;21(3):952. doi: 10.3390/ijms21030952. PMID:
32023927; PMCID: PMC7037706.
- Eisai presents full results of lecanemab Phase 3 confirmatory
Clarity AD study for early Alzheimer's disease at Clinical Trials
on Alzheimer's Disease (CTAD) conference. Available at:
https://www.eisai.co.jp/news/2022/news202285.html
- van Dyck, H., et al. Lecanemab in Early Alzheimer's Disease.
New England Journal of Medicine. 2023;388:9-21.
https://www.nejm.org/doi/full/10.1056/NEJMoa2212948.
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