Eisai and Biogen Announce Presentation of Additional Data From the
Phase II Clinical Trial of BAN2401 in Early Alzheimer’s Disease at
the 2018 Clinical Trials on Alzheimer’s Disease (CTAD)
Conference
Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”)
and Biogen Inc. (Nasdaq: BIIB) (Headquarters: Cambridge,
Massachusetts, United States, CEO: Michel Vounatsos, “Biogen”)
announced that Eisai presented the latest data from the Phase II
clinical study (Study 201) of BAN2401, an anti-amyloid beta
protofibril antibody, in 856 patients with early Alzheimer's
disease, at a symposium session titled “Clinical and Biomarker
Updates from BAN2401 Study 201 in Early Alzheimer’s Disease” held
on October 25 at the 11th Clinical Trials on Alzheimer’s Disease
(CTAD) conference in Barcelona, Spain.
Study 201 is a placebo-controlled, double-blind,
parallel-group, randomized study in 856 patients with mild
cognitive impairment (MCI) due to Alzheimer's disease (AD) or mild
Alzheimer's dementia (collectively known as early Alzheimer’s
disease) with confirmed amyloid pathology in the brain. Patients
were randomized to five dose regimens, 2.5 mg/kg bi-weekly, 5 mg/kg
monthly, 5 mg/kg bi-weekly, 10 mg/kg monthly and 10 mg/kg
bi-weekly, or placebo. This study used a Bayesian Adaptive
Randomization Design to automatically allocate newly enrolled
patients into the study to treatment arms showing higher
probability of efficacy based on the results of interim analyses.
The 10 mg/kg monthly and 10 mg/kg bi-weekly doses were determined
to have greater efficacy, and as a result, the proportion of
patients allocated to those treatment arms was greater.
Conventional statistical methods on predefined
clinical outcomes at the 18 month final efficacy time point
included Alzheimer’s Disease Composite Score (ADCOMS), Alzheimer's
Disease Assessment Scale-Cognitive subscale (ADAS-Cog), and
Clinical Dementia Rating Sum of Boxes (CDR-SB).
The most current data presented at CTAD 2018
highlight topline results, originally presented by Eisai in July at
the Alzheimer’s Association International Conference (AAIC) 2018,
as well as new data from pre-specified subgroup analyses and
cerebrospinal fluid (CSF) biomarkers. The full CTAD presentation is
available on the Investor Relations section of the Eisai
website.
From conventional statistical analysis of the
topline results, the highest treatment dose demonstrated a
statistically significant reduction in brain amyloid measured by
positron emission tomography (PET) at 18 months (p<0.0001). This
dose also showed a statistically significant slowing of clinical
decline on ADCOMS of 30 percent compared to placebo at 18 months
(p=0.034). A group-level correlation between clearance of brain
amyloid and slowing of clinical decline on ADCOMS was confirmed
(Pearson’s correlation coefficient of 0.838). A linear regression
model testing the slope of change from baseline on the rate of
disease progression using ADCOMS showed a significant difference
over 18 months (p<0.001) for the highest treatment dose versus
placebo, suggesting a potential disease-modifying effect.
A request from a health authority in July 2014
required an amendment to be implemented restricting enrollment of
APOE4 carriers in the highest treatment dose arm (10 mg/kg
bi-weekly), resulting in an imbalance of APOE4 carriers in that arm
versus placebo. To assess the influence of APOE4 status on the
observed effect in the highest treatment dose, the rates of
clinical decline for APOE4 carriers and non-carriers in the placebo
group were analyzed and shown not to be statistically significantly
different from each other on ADCOMS, ADAS-Cog and CDR-SB. Analysis
on clinical outcome measures was also conducted in pre-specified
subgroups of APOE4 status. At the highest treatment dose, APOE4
carriers treated with BAN2401 saw 63% less decline in disease
progression, while non-carriers saw 7% less decline, as measured by
ADCOMS versus placebo at 18 months. These results suggest that the
treatment effect for the 10 mg/kg bi-weekly dose is related to
treatment with BAN2401 and not due to an imbalance in subject
allocation by APOE4 status. In addition, the pooled 10 mg/kg
bi-weekly and 10 mg/kg monthly doses result in less decline on
ADCOMS versus placebo at 18 months (overall; 21%, APOE4 carriers;
25%, APOE4 non-carriers; 6%). More detailed results were presented
at CTAD.
Analyses of clinical outcome measures on
pre-specified subgroups, by clinical stage and by use of
concomitant Alzheimer’s disease medications, were also conducted.
Treatment with the highest treatment dose also resulted in less
decline in disease progression on ADCOMS at 18 months versus
placebo across subgroups of clinical stage (MCI due to AD subgroup;
33% and mild AD subgroup; 35%) and use of concomitant Alzheimer’s
disease medications (with concomitant AD meds; 23% and without
concomitant AD meds; 41%). The study was not powered to show
statistical significance in subgroups.
Exploratory data on CSF biomarkers of
neurodegeneration that are elevated in AD were also presented by
Eisai. To increase the sample size of the CSF subgroup,
analyses were conducted on samples from the combined 10 mg/kg
bi-weekly and 10 mg/kg monthly cohorts. From the results, markers
of synaptic damage (neurogranin), tau pathology
(phosphorylated-tau, p-Tau), and axonal degeneration (neurofilament
light chain, NFL) showed trends that are suggestive of impact on
underlying disease pathophysiology.
BAN2401 demonstrated an acceptable tolerability
profile through 18 months of study drug administration. The most
common treatment emergent adverse events were infusion-related
reactions and amyloid-related imaging abnormalities (ARIA), both of
which were dose-dependent. Incidence of ARIA-E (edema) was greater
in APOE4 carriers. Ten percent of ARIA-E cases (5 of 48 patients)
were symptomatic and included headache, visual disturbances, and
confusion. Sixty percent of ARIA-E occurred within the first three
months of treatment and approximately 89 percent of cases were mild
to moderate in severity.
Eisai and Biogen are currently discussing the
next steps for BAN2401 with regulatory authorities. An open-label
extension for patients previously enrolled in Study 201 is being
planned, with enrollment expected to begin this year.
This release discusses investigational uses of
an agent in development and is not intended to convey conclusions
about efficacy or safety. There is no guarantee that any
investigational uses of such product will successfully complete
clinical development or gain health authority approval.
Biogen Safe Harbor Statement
This press release contains forward-looking statements, including
statements made pursuant to the safe harbor provisions of the
Private Securities Litigation Reform Act of 1995 about results from
the Phase 2 study of BAN2401; the potential clinical effects of
BAN2401; risks and uncertainties associated with drug development
and commercialization; the potential benefits, safety and efficacy
of BAN2401 and therapies for other neurological diseases; the
timing and status of current and future regulatory filings; the
anticipated benefits and potential of Biogen’s collaboration
arrangements with Eisai; and the potential of Biogen’s commercial
business and pipeline programs, including BAN2401, elenbecestat and
aducanumab. These forward-looking statements may be accompanied by
words such as “aim,” “anticipate,” “believe,” “could,” “estimate,”
“expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “potential,”
“possible,” “will,” 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 trials may not be indicative of full results or results
from later stage or larger scale clinical trials and do not ensure
regulatory approval. You should not place undue reliance on these
statements or 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 trials; 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 BAN2401, elenbecestat, and/or aducanumab; the
occurrence of adverse safety events; risks of unexpected costs or
delays; the risks of other unexpected hurdles; uncertainty of
success in the development and potential commercialization of
BAN2401, elenbecestat, and/or aducanumab, which may be impacted by,
among other things, unexpected concerns that may arise from
additional data or analysis, the occurrence of adverse safety
events, failure to obtain regulatory approvals in certain
jurisdictions, failure to protect and enforce Biogen’s data,
intellectual property and other proprietary rights, and
uncertainties relating to intellectual property claims and
challenges; uncertainty as to whether the anticipated benefits and
potential of Biogen’s collaboration arrangement with Eisai can be
achieved; product liability claims; and third party collaboration
risks. 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 Securities and Exchange
Commission. These statements are based on Biogen’s current beliefs
and expectations and speak only as of the date of this press
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.
Media Inquiries |
Eisai Co., Ltd.Public Relations DepartmentTEL:
+81-(0)3-3817-5120Eisai Inc.Public Relations DepartmentTEL:
+1-201-746-2139 |
Biogen Inc.Public AffairsTEL: +1-781-464-3260
public.affairs@biogen.com |
<Notes to editors>
1. About BAN2401
BAN2401 is a humanized monoclonal antibody for
Alzheimer’s disease that is the result of a strategic research
alliance between Eisai and BioArctic. BAN2401 selectively binds to
neutralize and eliminate soluble, toxic Aβ aggregates that are
thought to contribute to the neurodegenerative process in
Alzheimer’s disease. As such, BAN2401 may have the potential to
have an effect on disease pathology and to slow down the
progression of the disease. Eisai obtained the global rights to
study, develop, manufacture and market BAN2401 for the treatment of
Alzheimer’s disease pursuant to an agreement concluded with
BioArctic in December 2007. In March 2014 Eisai and Biogen entered
into a joint development and commercialization agreement for
BAN2401 and the parties amended that agreement in October 2017.
2. About Study 201
Study 201 is a placebo-controlled, double-blind,
parallel-group, randomized Phase II clinical study in 856 patients
with mild cognitive impairment (MCI) due to Alzheimer's disease or
mild Alzheimer's dementia (collectively known as early Alzheimer’s
disease) with confirmed amyloid pathology in the brain. This study
used Bayesian Adaptive Randomization Design to automatically
allocate newly enrolled patients into the study to treatment arms
showing higher probability of efficacy based on the results of
interim analyses. The study design included five dose regimens and
placebo, and considered the efficacy of BAN2401 as well as dose
responsiveness through 16 interim analyses that assessed potential
for early success, an analysis based on ADCOMS at 12 months
(primary endpoint), and a comprehensive final analysis at 18 months
(secondary endpoints). Patients who received treatment with BAN2401
were randomized to five dose regimens, 2.5 mg/kg biweekly (52
patients), 5 mg/kg monthly (51 patients), 5 mg/kg biweekly (92
patients), 10 mg/kg monthly (253 patients), or 10 mg/kg biweekly
(161 patients). Biomarker endpoints included changes in Aβ
accumulated in the brain as measured by amyloid PET (positron
emission tomography) as well as in cerebrospinal fluid (CSF), while
ADCOMS (Alzheimer’s Disease Composite Score), Clinical Dementia
Rating Sum of Boxes (CDR-SB) and Alzheimer's Disease Assessment
Scale-cognitive subscale (ADAS-Cog) were measured as efficacy
endpoints (clinical).
3. About ADCOMS
Developed by Eisai, ADCOMS (AD Composite Score)
combines items from the ADAS-Cog (Alzheimer’s Disease Assessment
Scale-cognitive subscale), CDR-SB (Clinical Dementia Rating Sum of
Boxes) and the MMSE (Mini-Mental State Examination) scales to
enable a sensitive detection of changes in clinical functions of
early AD symptoms and changes in memory. This Study 201 utilizes
ADCOMS as its key endpoint for assessing clinical symptoms.
4. About Amyloid PET Imaging
Amyloid PET (Positron Emission Tomography)
imaging is a diagnostic method that enables the visualization of
amyloid plaque present in the brain as well as the quantitative
evaluation of amyloid plaque distribution and accumulation in the
brain via administration of a minute amount of PET tracer, which
specifically binds to amyloid plaque. Amyloid PET imaging enables
the assessment of pathology change and assistance of diagnosis of
patients with Alzheimer’s disease, including MCI due to AD, and
could predict clinical response.
5. About Correlation Coefficient
The correlation coefficient indicates the
strength of the relationship between two variables from two
quantitative data distributions. The correlation coefficient ranges
in value from -1 to 1, and as it approaches the absolute value of
1, it indicates a total positive linear correlation. In general, if
a correlation coefficient is 0.6 or greater, it suggests there is a
relationship between the variables.
6. About the Joint Development Agreement between Eisai
and Biogen for Alzheimer’s Disease
Eisai and Biogen are widely collaborating on the
joint development and commercialization of Alzheimer’s disease
treatments. Eisai serves as the lead in the co-development of
elenbecestat, a BACE inhibitor, and BAN2401, an anti-amyloid beta
(Aβ) protofibril antibody, while Biogen serves as the lead for
co-development of aducanumab, Biogen’s investigational anti-amyloid
beta (Aβ) antibody for patients with Alzheimer’s disease, and the
companies plan to pursue marketing authorizations for the three
compounds worldwide. If approved, the companies will also
co-promote the products in major markets, such as the United
States, the European Union and Japan.
As to BAN2401 and elenbecestat, both companies
will equally split overall costs, including research and
development expenses. Eisai will book all sales for elenbecestat
and BAN2401 following marketing approval and launch, and profits
will be equally shared between the companies.
7. About Eisai Co., Ltd.
Eisai Co., Ltd. is a leading global research and
development-based pharmaceutical company headquartered in Japan. We
define our corporate mission as “giving first thought to patients
and their families and to increasing the benefits health care
provides,” which we call our human health care (hhc) philosophy.
With approximately 10,000 employees working across our global
network of R&D facilities, manufacturing sites and marketing
subsidiaries, we strive to realize our hhc philosophy by delivering
innovative products to address unmet medical needs, with a
particular focus in our strategic areas of Neurology and
Oncology.
Leveraging the experience gained from the
development and marketing of Aricept®, a treatment for Alzheimer's
disease and dementia with Lewy bodies, Eisai has been working to
establish a social environment that involves patients in each
community in cooperation with various stakeholders including the
government, healthcare professionals and care workers, and is
estimated to have held over ten thousand dementia awareness events
worldwide. As a pioneer in the field of dementia treatment, Eisai
is striving to not only develop next generation treatments but also
to develop diagnosis methods and provide solutions.
For more information about Eisai Co., Ltd.,
please visit www.eisai.com.
8. About Biogen
At Biogen, our mission is clear: we are pioneers
in neuroscience. Biogen discovers, develops and delivers worldwide
innovative therapies for people living with serious neurological
and neurodegenerative diseases. One of the world’s first global
biotechnology companies, Biogen was founded in 1978 by Charles
Weissmann, Heinz Schaller, Kenneth Murray and Nobel Prize winners
Walter Gilbert and Phillip Sharp, and today has the leading
portfolio of medicines to treat multiple sclerosis, has introduced
the first and only approved treatment for spinal muscular atrophy
and is focused on advancing neuroscience research programs in
Alzheimer’s disease and dementia, multiple sclerosis and
neuroimmunology, movement disorders, neuromuscular disorders, pain,
ophthalmology, neuropsychiatry and acute neurology. Biogen also
manufactures and commercializes biosimilars of advanced
biologics.
We routinely post information that may be
important to investors on our website at www.biogen.com. To learn
more, please visit www.biogen.com and follow us on social media –
Twitter, LinkedIn, Facebook, YouTube.
9. About BioArctic AB
BioArctic AB (publ) is a Swedish research-based
biopharma company focusing on disease modifying treatments and
reliable biomarkers and diagnostics for neurodegenerative diseases,
such as Alzheimer’s disease and Parkinson’s disease. The company
also develops a potential treatment for Complete Spinal Cord
Injury. BioArctic focuses on innovative treatments in areas with
high unmet medical needs. The company was founded in 2003 based on
innovative research from Uppsala University, Sweden. Collaborations
with universities are of great importance to the company together
with our strategically important global partners in the Alzheimer
(Eisai) and Parkinson (AbbVie) projects. The project portfolio is a
combination of fully funded projects run in partnership with global
pharmaceutical companies and innovative in-house projects with
significant market- and out-licensing potential. BioArctic’s
B-share is listed on Nasdaq Stockholm Mid Cap (STO:BIOA B).
www.bioarctic.com.
Biogen (NASDAQ:BIIB)
Historical Stock Chart
From Mar 2024 to Apr 2024
Biogen (NASDAQ:BIIB)
Historical Stock Chart
From Apr 2023 to Apr 2024