TOKYO and CAMBRIDGE, Mass., June 09, 2024 (GLOBE NEWSWIRE) -- 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
monthly lecanemab-irmb (U.S. brand name: LEQEMBI(®)) intravenous (IV)
maintenance dosing. A Prescription Drug User Fee Act (PDUFA) action date is set
for January 25, 2025. LEQEMBI is indicated for the treatment of Alzheimer's
disease (AD) in patients with mild cognitive impairment or mild dementia stage
of disease (collectively referred to as early AD).
As part of the proposed monthly IV maintenance regimen, the patients who have
completed the biweekly IV initiation phase, exact period under discussion with
the FDA, would receive a monthly IV dose that maintains effective drug
concentration to sustain the clearance of highly toxic protofibrils* which can
continue to cause neuronal injury. The sBLA is based on modeling of observed
data from the Phase 2 study (Study 201) and its open-label extension (OLE) as
well as the Clarity AD study (Study 301) and its OLE study.
AD is a progressive disease caused by toxic amyloid proteins. Once established,
this pathophysiological process continues through the patient's life and
therefore sustained treatment may be necessary. In those who are eligible,
treatment should be initiated after diagnosis as early as possible to maximize
patient outcomes. Data from Studies 201, 301 and their OLEs show that continued
treatment with LEQEMBI beyond the 18-month core phase prolongs the benefit as
highly toxic protofibrils are continuously removed. If the sBLA is approved, the
clinical and biomarker benefits may be maintained through the once-monthly
dosing regimen that is less burdensome and easier for patients and care partners
to continue long-term.
Additionally, Eisai initiated the rolling submission of a BLA to the FDA for the
LEQEMBI subcutaneous autoinjector for weekly maintenance dosing after it was
granted Fast Track designation by the FDA in May 2024.
LEQEMBI is now approved in the U.S., Japan, China and South Korea, and
applications have been submitted for review in the European Union, Australia,
Brazil, Canada, Hong Kong, Great Britain, India, Israel, Russia, Saudi Arabia,
Taiwan, Singapore, and Switzerland.
Eisai serves as the lead for lecanemab's 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 believed to contribute to the brain injury that occurs with
AD and are considered to be the most toxic form of A?, 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 A? 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)
INDICATION
LEQEMBI(®) ((lecanemab-irmb) 100 mg/mL injection for intravenous use) is
indicated for the treatment of Alzheimer's disease (AD). Treatment with LEQEMBI
should be initiated in patients with mild cognitive impairment (MCI) or mild
dementia stage of disease, the population in which treatment was initiated in
clinical trials.
IMPORTANT SAFETY INFORMATION
+------------------------------------------------------------------------------+
|WARNING: AMYLOID-RELATED IMAGING ABNORMALITIES (ARIA) |
| |
| * Monoclonal antibodies directed against aggregated forms of amyloid beta, |
| including LEQEMBI, can cause ARIA, characterized as ARIA with edema (ARIA-|
| E) and ARIA with hemosiderin deposition (ARIA-H). Incidence and timing of |
| ARIA vary among treatments. ARIA usually occurs early in treatment and is |
| asymptomatic, although serious and life-threatening events, including |
| seizure and status epilepticus, rarely can occur. Serious intracerebral |
| hemorrhages >1 cm, some fatal, have been observed with this class of |
| medications. |
| |
| * Apolipoprotein E ?4 (ApoE ?4) Homozygotes: Patients who are ApoE ?4 |
| homozygotes (-15% of patients with AD) treated with this class of |
| medications have a higher incidence of ARIA, including symptomatic, |
| serious, and severe radiographic ARIA, compared to heterozygotes and |
| noncarriers. Testing for ApoE ?4 status should be performed prior to |
| initiation of treatment to inform the risk of developing ARIA. |
| Prescribers should discuss with patients the risk of ARIA across |
| genotypes and the implications of genetic testing results. Prescribers|
| should inform patients that if genotype testing is not performed, they|
| can still be treated with LEQEMBI; however, it cannot be determined if|
| they are ApoE ?4 homozygotes and at higher risk for ARIA. |
| |
| * Consider the benefit of LEQEMBI for the treatment of AD and the potential |
| risk of serious ARIA events when deciding to initiate treatment with |
| LEQEMBI. |
+------------------------------------------------------------------------------+
CONTRAINDICATION
LEQEMBI is contraindicated in patients with serious hypersensitivity to
lecanemab-irmb or to any of the excipients of LEQEMBI. Reactions have included
angioedema and anaphylaxis.
WARNINGS AND PRECAUTIONS
AMYLOID-RELATED IMAGING ABNORMALITIES
LEQEMBI can cause ARIA-E and ARIA-H, which can occur together. ARIA-E can be
observed on magnetic resonance imaging (MRI) as brain edema or sulcal effusions
and ARIA-H as microhemorrhage and superficial siderosis. ARIA can occur
spontaneously in patients with AD. With this class of medications, ARIA-H
generally occurs in association with ARIA-E. Reported ARIA symptoms may include
headache, confusion, visual changes, dizziness, nausea, and gait difficulty.
Focal neurologic deficits may also occur. Symptoms usually resolve over time.
Incidence of ARIA
Symptomatic ARIA occurred in 3% (29/898) and serious ARIA symptoms in 0.7%
(6/898) with LEQEMBI. Clinical ARIA symptoms resolved in 79% (23/29) of patients
during the period of observation. ARIA, including asymptomatic radiographic
events, was observed: LEQEMBI, 21% (191/898); placebo, 9% (84/897). ARIA-E was
observed: LEQEMBI, 13% (113/898); placebo, 2% (15/897). ARIA-H was observed:
LEQEMBI, 17% (152/898); placebo, 9% (80/897). No increase in isolated ARIA-H was
observed for LEQEMBI vs placebo.
ApoE ?4 Carrier Status and Risk of ARIA
Of the patients taking LEQEMBI, 16% (141/898) were ApoE ?4 homozygotes, 53%
(479/898) were heterozygotes, and 31% (278/898) were noncarriers. With LEQEMBI,
the incidence of ARIA was higher in ApoE ?4 homozygotes (LEQEMBI: 45%; placebo:
22%) than in heterozygotes (LEQEMBI: 19%; placebo: 9%) and noncarriers (LEQEMBI:
13%; placebo: 4%). Symptomatic ARIA-E occurred in 9% of ApoE ?4 homozygotes vs
2% of heterozygotes and 1% of noncarriers. Serious ARIA events occurred in 3% of
ApoE ?4 homozygotes and in -1% of heterozygotes and noncarriers. The
recommendations on management of ARIA do not differ between ApoE ?4 carriers and
noncarriers.
Radiographic Findings
The majority of ARIA-E radiographic events occurred within the first 7 doses,
although ARIA can occur at any time, and patients can have >1 episode. Maximum
radiographic severity of ARIA-E with LEQEMBI was mild in 4% (37/898), moderate
in 7% (66/898), and severe in 1% (9/898) of patients. Resolution of ARIA-E on
MRI occurred in 52% of patients by 12 weeks, 81% by 17 weeks, and 100% overall
after detection. Maximum radiographic severity of ARIA-H microhemorrhage with
LEQEMBI was mild in 9% (79/898), moderate in 2% (19/898), and severe in 3%
(28/898) of patients; superficial siderosis was mild in 4% (38/898), moderate in
1% (8/898), and severe in 0.4% (4/898) of patients. With LEQEMBI, the rate of
severe radiographic ARIA-E was highest in ApoE ?4 homozygotes (5%; 7/141) vs
heterozygotes (0.4%; 2/479) or noncarriers (0%; 0/278). With LEQEMBI, the rate
of severe radiographic ARIA-H was highest in ApoE ?4 homozygotes (13.5%;
19/141) vs heterozygotes (2.1%; 10/479) or noncarriers (1.1%; 3/278).
Intracerebral Hemorrhage
Intracerebral hemorrhage >1 cm in diameter was reported in 0.7% (6/898) with
LEQEMBI vs 0.1% (1/897) with placebo. Fatal events of intracerebral hemorrhage
in patients taking LEQEMBI have been reported.
Concomitant Antithrombotic Medication:
In Clarity AD, baseline use of antithrombotic medication (aspirin, other
antiplatelets, or anticoagulants) was allowed if the patient was on a stable
dose. The majority of exposures to antithrombotic medications were to aspirin.
Antithrombotic medications did not increase the risk of ARIA with LEQEMBI. The
incidence of intracerebral hemorrhage was 0.9% (3/328) in patients taking
LEQEMBI with a concomitant antithrombotic medication at the time of the event vs
0.6% (3/545) in those who did not receive an antithrombotic. Patients taking
LEQEMBI with an anticoagulant alone or combined with an antiplatelet medication
or aspirin had an incidence of intracerebral hemorrhage of 2.5% (2/79) vs none
in patients receiving placebo. Caution should be exercised when considering the
administration of anticoagulants or a thrombolytic agent (e.g., tissue
plasminogen activator) to a patient already being treated with LEQEMBI.
Other Risk Factors for Intracerebral Hemorrhage:
Patients were excluded from enrollment in Clarity AD for findings on
neuroimaging that indicated an increased risk for intracerebral hemorrhage.
These included findings suggestive of cerebral amyloid angiopathy (prior
cerebral hemorrhage >1 cm in greatest diameter, >4 microhemorrhages, superficial
siderosis, vasogenic edema) or other lesions (aneurysm, vascular malformation).
The presence of an ApoE ?4 allele is also associated with cerebral amyloid
angiopathy. Caution should be exercised when considering the use of LEQEMBI in
patients with factors that indicate an increased risk for intracerebral
hemorrhage and in patients who need to be on anticoagulant therapy.
ARIA Monitoring and Dose Management Guidelines
Obtain a recent baseline brain MRI prior to initiating treatment with LEQEMBI
and prior to the 5th, 7th, and 14th infusions. Enhanced clinical vigilance for
ARIA is recommended during the first 14 weeks of treatment with LEQEMBI.
Depending on ARIA-E and ARIA-H clinical symptoms and radiographic severity, use
clinical judgment when considering whether to continue dosing or to temporarily
or permanently discontinue LEQEMBI. If a patient experiences ARIA symptoms,
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.
HYPERSENSITIVITY REACTIONS
Hypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis,
have occurred with LEQEMBI. Promptly discontinue the infusion upon the first
observation of any signs or symptoms consistent with a hypersensitivity reaction
and initiate appropriate therapy.
INFUSION-RELATED REACTIONS (IRRs)
IRRs were observed-LEQEMBI: 26% (237/898); placebo: 7% (66/897)-and the majority
of cases with LEQEMBI (75%, 178/237) occurred with the first infusion. IRRs were
mostly mild (69%) or moderate (28%) in severity. IRRs resulted in
discontinuation of LEQEMBI in 1% (12/898). Symptoms of IRRs included fever and
flu-like symptoms (chills, generalized aches, feeling shaky, and joint pain),
nausea, vomiting, hypotension, hypertension, and oxygen desaturation.
In the event of an IRR, the infusion rate may be reduced or the infusion may be
discontinued and appropriate therapy initiated as clinically indicated. Consider
prophylactic treatment prior to future infusions with antihistamines,
acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids.
ADVERSE REACTIONS
The most common adverse reaction leading to discontinuation of LEQEMBI was ARIA-
H microhemorrhages that led to discontinuation in 2% (15/898) with LEQEMBI vs
=5% with LEQEMBI (N=898) and >=2%
higher than placebo (N=897) were IRRs (LEQEMBI: 26%; placebo: 7%), ARIA-H
(LEQEMBI: 14%; placebo: 8%), ARIA-E (LEQEMBI: 13%; placebo: 2%), headache
(LEQEMBI: 11%; placebo: 8%), superficial siderosis of central nervous system
(LEQEMBI: 6%; placebo: 3%), rash (LEQEMBI: 6%; placebo: 4%), and nausea/vomiting
(LEQEMBI: 6%; placebo: 4%).
Please see full Prescribing Information (https://www.leqembihcp.com/about-
leqembi/mechanism-of-action) for LEQEMBI, including Boxed WARNING.
MEDIA CONTACTS
Eisai Co., Ltd.
Public Relations Department
TEL: +81 (0)3-3817-5120
Eisai Inc. (U.S.)
Julie Edelman
1-862-213-5915
Julie_Edelman@eisai.com
Eisai Europe, Ltd. Biogen Inc.
EMEA Communications Department Jack Cox
+44 (0) 786 601 1272 + 1-781-464-3260
Emea-comms@eisai.net (mailto:Emea- public.affairs@biogen.com
comms@eisai.net) (mailto:public.affairs@biogen.com)
INVESTOR CONTACTS
Biogen Inc.
Chuck Triano
Eisai Co., Ltd. + 1-781-464-2442
Investor Relations Department IR@biogen.com
TEL: +81 (0) 3-3817-5122 (mailto:IR@biogen.com)
Notes to Editors
1. 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 (A?).(3) Lecanemab is approved in the U.S.,(4) Japan,(5) China(6)
and South Korea(7). In the U.S., Japan, China and South Korea, the indications
are as follows.
* U.S.: For the treatment of Alzheimer's disease (AD). It should be initiated
in patients with MCI or mild dementia stage of disease.(4)
* Japan: For slowing progression of MCI and mild dementia due to AD.(5)
* China: For the treatment of MCI due to AD and mild AD dementia.(6)
* South Korea: For the treatment in adult patients with MCI due to AD or Mild
AD.(7)
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.(3) 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.(8) 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; P10%) in
the lecanemab group were infusion reactions, ARIA-H (combined cerebral
microhemorrhages, cerebral macrohemorrhages, and superficial siderosis), ARIA-E
(edema/effusion), headache, and fall.(8)
Eisai has also submitted applications for approval of lecanemab in 13 countries
and regions, including the European Union (EU).
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.
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 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 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
(https://www.eisai.com/index.html)(for global headquarters: Eisai Co., Ltd.),
and connect with us on X (https://twitter.com/Eisai_SDGs), LinkedIn
(https://www.linkedin.com/company/eisaiglobal/) and Facebook
(https://www.facebook.com/EisaiGlobal/). The website and social media channels
are intended for audiences outside of the UK and Europe. For audiences based in
the UK and Europe, please visit www.eisai.eu (http://www.eisai.eu) and Eisai
EMEA LinkedIn (https://www.linkedin.com/company/eisai-emea/).
5. About Biogen
Founded in 1978, Biogen is a leading biotechnology company that pioneers
innovative science to deliver new medicines to transform patients' lives and to
create value for shareholders and our communities. We apply deep understanding
of human biology and leverage different modalities to advance first-in-class
treatments or therapies that deliver superior outcomes. Our approach is to take
bold risks, balanced with return on investment to deliver long-term growth.
The company routinely posts information that may be important to investors on
its website at www.biogen.com (http://www.biogen.com/). Follow Biogen on social
media - Facebook
(https://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.facebook.c
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(https://twitter.com/biogen), YouTube
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Biogen Safe Harbor
This news release contains forward-looking statements, 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.
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; 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; and third
party collaboration risks, 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 speak only as of the date of this news release. Biogen does not
undertake any obligation to publicly update any forward-looking statements.
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events/press-announcements/fda-grants-accelerated-approval-alzheimers-
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https://www.eisai.com/news/2024/news202403.html. Last accessed: March 2024.
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