Additional Detailed Analyses From Phase 2 Study 201 of Lecanemab
Published as Three Papers in Peer-Reviewed Journals
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 three additional detailed analyses from the Phase IIb
clinical study (Study 201), evaluating the efficacy and safety of
lecanemab for mild cognitive impairment (MCI) due to Alzheimer’s
disease (AD) and mild AD (collectively known as early AD), were
published in the peer-reviewed journals.
- Detailed results on biomarker, cognitive, and clinical effects
from Study 201 core to OLE (open-label extension): Alzheimer's
Research and Therapy
- Consistency of efficacy results across various clinical
measures and statistical methods in Study 201: Alzheimer's Research
and Therapy
- ARIA (amyloid-related imaging abnormality) profile in Study
201: Alzheimer's & Dementia: Translational Research and
Clinical Interventions
Study 201 was a multicenter, double-blind,
placebo-controlled, Phase 2b trial conducted in 856 patients with
early AD. Its core study evaluated key efficacy assessments,
including clinical change on the AD Composite Score (ADCOMS) as the
primary endpoint at 12 months and as key secondary endpoints,
ADCOMS, Clinical Dementia Rating-Sum-of-Boxes (CDR-SB) and AD
Assessment Scale-Cognitive Subscale 14 (ADAS-Cog14) at 18 months.
Following analysis of the 18-month core phase, an intervening
off-treatment period (gap period) ranging from 9-59 months (mean 24
months) was taken, which was followed by an OLE with 10 mg/kg IV
bi-weekly lecanemab dosing to assess long-term safety and
tolerability. The results of the primary analysis in the core study
including clinical efficacy and biomarkers have already been
published, showing a consistent reduction in clinical decline
across several clinical and biomarker endpoints with lecanemab 10
mg/kg bi-weekly dosing.
1. Detailed results on biomarker,
cognitive, and clinical effects from Study 201.“Lecanemab
in patients with early Alzheimer’s disease: detailed results on
biomarker, cognitive, and clinical effects from the randomized and
open‑label extension of the phase 2 proof‑of‑concept study”In the
core 201 study, lecanemab was shown to reduce brain Aβ accumulation
measured by amyloid PET in a dose- and time-dependent manner after
12 and 18 months of treatment, and corresponding changes in plasma
biomarkers and reduction in clinical decline. During the gap
period, a trend was observed for plasma Aβ42/40 ratio and p-tau181
values to return to the pre-administration levels (re-accumulation)
faster than amyloid PET.
In the OLE, lecanemab 10 mg/kg biweekly
treatment showed a decrease in brain amyloid beta (Aβ) accumulation
measured by amyloid PET, a decrease in the plasma Aβ42/40 ratio,
and a decrease in plasma p-tau181.
The potential for disease modification with
lecanemab is supported by an increasing difference in clinical
measures between the lecanemab group and placebo group in line with
time during the core period, differences in clinical progression
between subjects who received 10 mg/kg lecanemab and those who
received placebo in the core period, which remained persistent
throughout the gap period, and an impact on biological measures
that reflect key pathophysiological changes in AD. Furthermore, the
results showed the potential for monitoring the treatment effects
of lecanemab using plasma biomarkers.
2. Consistency of efficacy results
across various clinical measures and statistical methods in Study
201.“Consistency of efficacy results across various
clinical measures and statistical methods in the lecanemab phase 2
trial of early Alzheimer’s disease”In order to assess the
robustness of lecanemab's efficacy in Study 201, sensitivity
analyses were performed using several statistical models for three
key clinical endpoints (ADCOMS, CDR-SB, ADAS-Cog14). The
sensitivity analysis showed that 18 months of lecanemab treatment
consistently reduced the clinical decline in all statistical models
examined. The results of all sensitivity analyses for three key
clinical endpoints at the highest dose (10 mg/kg bi-weekly) at 18
months were consistent, with a 29.1% to 37.4% reduction in clinical
deterioration with lecanemab compared to placebo for ADCOMS, 26.5%
to 38.4% for CDR-SB and 37.4% to 55.9% for ADAS-Cog14.
3. ARIA profile in Study
201“ARIA in patients treated with lecanemab (BAN2401) in a
phase 2 study in early Alzheimer’s disease”In the core study 201,
amyloid-related imaging abnormalities-edema (ARIA-E) was dose
dependent, with an incidence 9.9% at the highest doses (10 mg/kg
bi-weekly) for the overall population and 14.3% for ApoE4 positive
subjects. Most ARIA-E occurred within 30 days after the initial
dose and had mild to moderate severity in radiographic severity.
Symptomatic ARIA-E occurred in 3% of participants in the 10mg/kg
bi-weekly treatment group. ARIA cerebral microhemorrhages,
intracerebral hemorrhage >1cm, and superficial siderosis
(ARIA-H) occurred in 6.2% of subjects who received 10 mg/kg
biweekly lecanemab and those events were mostly mild in severity.
There were no symptomatic cases of ARIA-H reported in the core
study.
Overall ARIA-E events in the OLE phase were
generally consistent with the rate seen in the lecanemab 10 mg/kg
biweekly group in the core study (four subjects treated with
placebo in the core study had ARIA-E in the OLE (4 of 45: 8.9%). As
with the core study, most ARIA-E occurred within 3 months after
receiving the initial dose in the OLE and had mostly mild to
moderate in radiographic severity. ARIA-H events in the OLE were
generally consistent with the rate seen in the lecanemab 10 mg/kg
biweekly group in the core study. ARIA-H events were mostly mild or
moderate in severity. One symptomatic case of ARIA-H, intracerebral
hemorrhage > 1cm, was reported in OLE. This subject did not have
concurrent ARIA-E, and the adverse event resolved with residual
visual field defect.
PK/PD modeling showed that the incidence of
ARIA-E was correlated with Cmax at steady state. Based on the
fact that lecanemab was generally well tolerated at the highest
dose in this study, the Phase 3 Clarity AD study was conducted
without dose titration. A subcutaneous formulation that may
potentially reduce the Cmax of lecanemab is being developed and
evaluated to determine if there is a reduction of the incidence of
ARIA-E compared to intravenous formulation.
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.
To learn more, visit www.LEQEMBI.com.
Contacts |
MEDIA CONTACT:Eisai Co., Ltd.Public Relations DepartmentTEL:
+81-(0)3-3817-5120Eisai Inc. (U.S.)Libby Holman+
1-201-753-1945Libby_Holman@eisai.com Eisai Europe, Ltd.(UK,
Europe, Australia, New Zealand and Russia) EMEA Communications
Department+44 (0) 786 601 1272EMEA-comms@eisai.netINVESTOR
CONTACT:Eisai Co., Ltd.Investor Relations DepartmentTEL: +81 (0)
3-3817-5122 |
MEDIA CONTACT:Biogen Inc.Natacha Gassenbach +
1-857-777-6573public.affairs@biogen.com INVESTOR
CONTACT:Biogen Inc.Mike Hencke+ 1-781-464-2442IR@biogen.com |
[Notes to editors]
1. About
LecanemabLecanemab (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). Lecanemab
selectively binds and eliminates Aβ protofibrils that are thought
to contribute to the neurotoxicity in AD. As such, lecanemab may
have the potential to have an effect on disease pathology and to
slow down the progression of the disease. LEQEMBI is indicated for
the treatment of Alzheimer’s disease (AD) in the U.S. under an
accelerated approval by the U.S. Food and Drug Administration
(FDA). 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. The
Clarity AD study of lecanemab met its primary endpoint and all key
secondary endpoints with highly statistically significant
results.
Please see full Prescribing Information in the
United States.
Lecanemab-irmb 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 FDA
determined that the results of the Phase 3 Clarity AD study can
serve as the confirmatory study to verify the clinical benefit of
lecanemab. In November 2022, the results of 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.
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. 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. 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 has completed a lecanemab subcutaneous
bioavailability study, and subcutaneous dosing is currently being
evaluated in the Clarity AD 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, has been 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 the
Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led
by Washington University School of Medicine in St. Louis, has been
ongoing.
2. About the
Collaboration between Eisai and Biogen for ADEisai 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
ADSince 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
BiogenFounded 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 HarborThis 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.
Biogen (TG:IDP)
Historical Stock Chart
From Jun 2024 to Jul 2024
Biogen (TG:IDP)
Historical Stock Chart
From Jul 2023 to Jul 2024