FDA Accepts Eisai’s Submitting of a Supplemental Biologics License Software and Grants Precedence Overview for Conventional Approval of LEQEMBI (lecanemab-irmb) for

Confirmatory Section 3 Readability AD knowledge to be evaluated by FDA in figuring out whether or not to transform accelerated approval of LEQEMBI to a standard approval

Precedence Overview accelerates FDA evaluation time with a Prescription Drug Consumer Payment Act (PDUFA) goal motion on July 6, 2023

TOKYO and CAMBRIDGE, Mass., March 5, 2023 /PRNewswire/ — Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and Biogen Inc. (Nasdaq: BIIB, Company headquarters: Cambridge, Massachusetts, CEO: Christopher A. Viehbacher, “Biogen”) introduced as we speak that the U.S. Meals and Drug Administration (FDA) has accepted Eisai’s supplemental Biologics License Software (sBLA) for LEQEMBI™ (lecanemab-irmb) 100 mg/mL injection for intravenous use, supporting the conversion of the accelerated approval of LEQEMBI to a standard approval. The LEQEMBI utility has been granted Precedence Overview, with a Prescription Drug Consumer Payment Act (PDUFA) motion date of July 6, 2023. The FDA is presently planning to carry an Advisory Committee to debate this utility however has not but publicly introduced the date of the assembly.

LEQEMBI is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed in opposition to aggregated soluble (protofibrils*) and insoluble types of amyloid beta (Aβ), accepted underneath the Accelerated Approval Pathway for the therapy of Alzheimer’s Illness (AD) on January 6, 2023. Remedy with LEQEMBI ought to solely be initiated in sufferers with the gentle cognitive impairment or gentle dementia stage of illness and confirmed presence of Aβ pathology. On the identical day that LEQEMBI acquired its accelerated approval, Eisai submitted the sBLA to the FDA for approval underneath the standard pathway.

The sBLA relies on the findings from Eisai’s lately revealed massive, world confirmatory Section 3 scientific trial, Readability AD. LEQEMBI met the first endpoint and all key secondary endpoints with extremely statistically important outcomes. In November 2022, outcomes of the Readability AD examine had been offered on the Medical Trials on Alzheimer’s Illness (CTAD) convention and concurrently revealed within the peer-reviewed medical journal, The New England Journal of Medication.

LEQEMBI was accepted underneath accelerated approval within the U.S. and was launched within the U.S. on January 18, 2023. The accelerated approval was primarily based on Section 2 knowledge that demonstrated that LEQEMBI decreased the buildup of Aβ plaque within the mind, a defining characteristic of AD, and its continued approval could also be contingent upon verification of LEQEMBI’s scientific profit in a confirmatory trial. The FDA has decided that the outcomes of Readability AD can function the confirmatory examine to confirm the scientific advantage of lecanemab. 

Eisai serves because the lead of LEQEMBI improvement and regulatory submissions globally with each Eisai and Biogen co-commercializing and co-promoting the product and Eisai having ultimate decision-making authority.

* Protofibrils are massive Aβ aggregated soluble species of 75-500 Kd.¹

To study extra, go to www.LEQEMBI.com.

INDICATION, DOSAGE AND ADMINISTRATION, AND IMPORTANT SAFETY INFORMATION IN THE U.S.

INDICATION
LEQEMBI is indicated for the therapy of Alzheimer’s illness. Remedy with LEQEMBI needs to be initiated in sufferers with gentle cognitive impairment or gentle dementia stage of illness, the inhabitants through which therapy was initiated in scientific trials. There are not any security or effectiveness knowledge on initiating therapy at earlier or later phases of the illness than had been studied. This indication is accepted underneath accelerated approval primarily based on discount in amyloid beta plaques noticed in sufferers handled with LEQEMBI. Continued approval for this indication could also be contingent upon verification of scientific profit in a confirmatory trial.

IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS

Amyloid Associated Imaging Abnormalities

• LEQEMBI may cause amyloid associated imaging abnormalities-edema (ARIA-E) and -hemosiderin deposition (ARIA-H). ARIA-E could be noticed on MRI as mind edema or sulcal effusions, and ARIA-H as microhemorrhage and superficial siderosis. ARIA is normally asymptomatic, though critical and life-threatening occasions, together with seizure and standing epilepticus, hardly ever can happen. Reported signs related to ARIA might embrace headache, confusion, visible adjustments, dizziness, nausea, and gait issue. Focal neurologic deficits may happen. Signs related to ARIA normally resolve over time.

ARIA Monitoring and Dose Administration Pointers

• Get hold of current (inside one 12 months) mind magnetic resonance imaging (MRI) previous to initiating therapy with LEQEMBI. Get hold of an MRI previous to the fifth, seventh, and 14th infusions.
• Suggestions for dosing in sufferers with ARIA-E and ARIA-H rely upon scientific signs and radiographic severity. Relying on ARIA severity, use scientific judgment in contemplating whether or not to proceed dosing, briefly discontinue therapy, or completely discontinue LEQEMBI.
• Enhanced scientific vigilance for ARIA is really useful throughout the first 14 weeks of therapy with LEQEMBI. If a affected person experiences signs suggestive of ARIA, scientific analysis needs to be carried out, together with MRI if indicated. If ARIA is noticed on MRI, cautious scientific analysis needs to be carried out previous to persevering with therapy.
• There isn’t any expertise in sufferers who continued dosing by way of symptomatic ARIA-E or by way of asymptomatic, however radiographically extreme, ARIA-E. There’s restricted expertise in sufferers who continued dosing by way of asymptomatic however radiographically gentle to average ARIA-E. There are restricted knowledge in dosing sufferers who skilled recurrent ARIA-E.

Incidence of ARIA

• In Examine 1 (Examine 201), symptomatic ARIA occurred in 3% (5/161) of LEQEMBI-treated sufferers. Medical signs related to ARIA resolved in 80% of sufferers throughout the interval of statement.
• Together with asymptomatic instances, ARIA was noticed in LEQEMBI: 12% (20/161); placebo: 5% (13/245). ARIA-E was noticed in LEQEMBI: 10% (16/161); placebo: 1% (2/245). ARIA-H was noticed in LEQEMBI: 6% (10/161); placebo: 5% (12/245). There was no improve in remoted ARIA-H for LEQEMBI in comparison with placebo.
• Intracerebral hemorrhage >1 cm in diameter was reported after one therapy in LEQEMBI: 1 affected person; placebo: zero sufferers. Occasions of intracerebral hemorrhage, together with deadly occasions, in sufferers taking LEQEMBI have additionally been reported in different research.

Apolipoprotein E ε4 (ApoE ε4) Provider Standing and Threat of ARIA

• In Examine 1, 6% (10/161) of sufferers within the LEQEMBI group had been ApoE ε4 homozygotes, 24% (39/161) had been heterozygotes, and 70% (112/161) had been noncarriers.
• The incidence of ARIA was greater in ApoE ε4 homozygotes than in heterozygotes and noncarriers amongst sufferers handled with LEQEMBI. Of the 5 LEQEMBI-treated sufferers who had symptomatic ARIA, 4 had been ApoE ε4 homozygotes, 2 of whom skilled extreme signs. An elevated incidence of symptomatic and total ARIA in ApoE ε4 homozygotes in comparison with heterozygotes and noncarriers in LEQEMBI-treated sufferers has been reported in different research.
• The suggestions on administration of ARIA don’t differ between ApoE ε4 carriers and noncarriers.
• Think about testing for ApoE ε4 standing to tell the danger of creating ARIA when deciding to provoke therapy with LEQEMBI.

Radiographic Findings

• The vast majority of ARIA-E radiographic occasions occurred early in therapy (inside the first 7 doses), though ARIA can happen at any time and sufferers can have greater than 1 episode. The utmost radiographic severity of ARIA-E in sufferers handled with LEQEMBI was gentle in 4% (7/161) of sufferers, average in 4% (7/161) of sufferers, and extreme in 1% (2/161) of sufferers. Decision on MRI occurred in 62% of ARIA-E sufferers by 12 weeks, 81% by 21 weeks, and 94% total after detection. The utmost radiographic severity of ARIA-H microhemorrhage in sufferers handled with LEQEMBI was gentle in 4% (7/161) of sufferers and extreme in 1% (2/161) of sufferers; 1 of the ten sufferers with ARIA-H had gentle superficial siderosis.

Concomitant Antithrombotic Treatment and Different Threat Components for Intracerebral Hemorrhage

• Sufferers had been excluded from enrollment in Examine 1 for baseline use of anticoagulant drugs. Antiplatelet drugs reminiscent of aspirin and clopidogrel had been allowed. If anticoagulant remedy was used due to intercurrent medical occasions that required therapy for ≤4 weeks, therapy with LEQEMBI was to be briefly suspended.
• Most exposures to antithrombotic drugs had been to aspirin; few sufferers had been uncovered to different antiplatelet medicine or anticoagulants, limiting any significant conclusions concerning the threat of ARIA or intracerebral hemorrhage in sufferers taking different antiplatelet medicine or anticoagulants. As a result of intracerebral hemorrhages >1 cm in diameter have been noticed in sufferers taking LEQEMBI, further warning needs to be exercised when contemplating the administration of antithrombotics or a thrombolytic agent (e.g., tissue plasminogen activator) to a affected person already being handled with LEQEMBI.
• Sufferers had been excluded from enrollment in Examine 1 for the next threat components for intracerebral hemorrhage: prior cerebral hemorrhage >1 cm in biggest diameter, greater than 4 microhemorrhages, superficial siderosis, proof of vasogenic edema, proof of cerebral contusion, aneurysm, vascular malformation, infective lesions, a number of lacunar infarcts or stroke involving a significant vascular territory, and extreme small vessel or white matter illness. Warning needs to be exercised when contemplating the usage of LEQEMBI in sufferers with these threat components.

Infusion-Associated Reactions

• Infusion-related reactions had been noticed in LEQEMBI: 20% (32/161); placebo: 3% (8/245); and the vast majority of instances in LEQEMBI-treated sufferers (88%, 28/32) occurred with the primary infusion. All infusion-related reactions had been gentle (56%) or average (44%) in severity. Infusion-related reactions resulted in discontinuations in 2% (4/161) of sufferers handled with LEQEMBI. Signs of infusion-related reactions included fever and flu-like signs (chills, generalized aches, feeling shaky, and joint ache), nausea, vomiting, hypotension, hypertension, and oxygen desaturation.
• After the primary infusion, 38% of LEQEMBI-treated sufferers had transient decreased lymphocyte counts to <0.9 x10⁹/L in comparison with 2% on placebo, and 22% of LEQEMBI-treated sufferers had transient elevated neutrophil counts to >7.9 x10⁹/L in comparison with 1% on placebo.
• Within the occasion of an infusion-related response, the infusion charge could also be decreased, or the infusion could also be discontinued, and applicable remedy initiated as clinically indicated. Prophylactic therapy with antihistamines, acetaminophen, nonsteroidal anti-inflammatory medicine, or corticosteroids previous to future infusions could also be thought-about.

ADVERSE REACTIONS

• In Examine 1, 15% of LEQEMBI-treated sufferers, in comparison with 6% of placebo-treated sufferers, stopped examine therapy due to an adversarial response. The most typical adversarial response resulting in discontinuation of LEQEMBI was infusion-related reactions that led to discontinuation in 2% (4/161) of sufferers handled with LEQEMBI in comparison with 1% (2/245) of sufferers on placebo.
• The most typical adversarial reactions reported in ≥5% of sufferers handled with LEQEMBI (N=161) and ≥2% greater than placebo (N=245) in Examine 1 had been 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 Data within the U. S.

(Notes to editors)

1.  About LEQEMBI^_™ (lecanemab-irmb)
LEQEMBI™ (lecanemab-irmb) is the results of a strategic analysis alliance between Eisai and BioArctic. LEQEMBI is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed in opposition to aggregated soluble (protofibril) and insoluble types of amyloid-beta (Aβ). Within the U.S., LEQEMBI was granted accelerated approval by the U.S. Meals and Drug Administration (FDA) on January 6, 2023. LEQEMBI is indicated for the therapy of Alzheimer’s illness (AD) within the U.S. Remedy with LEQEMBI needs to be initiated in sufferers with gentle cognitive impairment or gentle dementia stage of illness, the inhabitants through which therapy was initiated in scientific trials. There are not any security or effectiveness knowledge on initiating therapy at earlier or later phases of the illness than had been studied. This indication is accepted underneath accelerated approval primarily based on discount in Aβ plaques noticed in sufferers handled with LEQEMBI. Continued approval for this indication could also be contingent upon verification of scientific profit in a confirmatory trial.

Within the U.S., Eisai submitted a supplemental Biologics License Software (sBLA) to the FDA for approval underneath the standard pathway on January 6, 2023. The Readability AD examine of lecanemab met its major endpoint and all key secondary endpoints with extremely statistically important outcomes. Eisai submitted an utility for manufacturing and advertising approval to the Prescribed drugs and Medical Gadgets Company (PMDA) on January 16, 2023, in Japan. The Precedence Overview was granted by the Ministry of Well being, Labour and Welfare (MHLW) on January 26, 2023. Eisai utilized the prior evaluation session system of PMDA, with the purpose of shortening the evaluation interval for lecanemab. In Europe, Eisai submitted a advertising authorization utility (MAA) to the European Medicines Company (EMA) on January 9, 2023, and accepted on January 26, 2023. In China, Eisai initiated submission of knowledge for a BLA to the Nationwide Medical Merchandise Administration (NMPA) of China in December 2022, and the Precedence Overview was granted on February 27, 2023.

Eisai has accomplished lecanemab subcutaneous bioavailability examine, and subcutaneous dosing is presently being evaluated within the Readability AD OLE.

Since July 2020, Eisai’s Section 3 scientific examine (AHEAD 3-45) for people with preclinical AD, which means they’re clinically regular and have intermediate or elevated ranges of amyloid of their brains, is ongoing. AHEAD 3-45 is carried out as a public-private partnership between the Alzheimer’s Medical Trial Consortium (ACTC) that gives the infrastructure for tutorial scientific trials in AD and associated dementias within the U.S., funded by the Nationwide Institute on Growing old, a part of the Nationwide Institutes of Well being, Eisai and Biogen. The Tau NexGen scientific examine for Dominantly Inherited AD (DIAD), that’s carried out by Dominantly Inherited Alzheimer Community Trials Unit (DIAN-TU), led by Washington College College of Medication in St. Louis, has been ongoing since January 2022.

2.  Concerning the Collaboration between Eisai and Biogen for AD
Eisai and Biogen have been collaborating on the joint improvement and commercialization of AD therapies since 2014. Eisai serves because the lead of lecanemab improvement and regulatory submissions globally with each corporations co-commercializing and co-promoting the product and Eisai having ultimate decision-making authority.

3.  About the Collaboration between Eisai and BioArctic for AD
Since 2005, Eisai and BioArctic have had a long-term collaboration concerning the event and commercialization of AD therapies. Eisai obtained the worldwide rights to review, develop, manufacture and market LEQEMBI for the therapy of AD pursuant to an settlement with BioArctic in December 2007. The event and commercialization settlement on the antibody LEQEMBI back-up was signed in Might 2015.

4.  About Eisai Co., Ltd.
Eisai’s Company Idea is “to offer first thought to sufferers and folks within the every day residing area, and to extend the advantages that well being care supplies.” Underneath this idea (also referred to as the human well being care (hhc) idea), we purpose to successfully obtain social good within the type of relieving anxiousness over well being and decreasing well being disparities. With a worldwide community of R&D amenities, manufacturing websites and advertising subsidiaries, we try to create and ship modern merchandise to focus on illnesses with excessive unmet medical wants, with a specific focus in our strategic areas of neurology and oncology.

In addition, we reveal our dedication to the elimination of uncared for tropical illnesses (NTDs), which is a goal (3.3) of the United Nations Sustainable Growth Targets (SDGs), by engaged on varied actions along with world companions.

For extra details about Eisai, please go to www.eisai.com (for world headquarters: Eisai Co., Ltd.), and join with us on Twitter @Eisai_SDGs.

5.  About Biogen
Based in 1978, Biogen is a number one world biotechnology firm that has pioneered a number of breakthrough improvements together with a broad portfolio of medicines to deal with a number of sclerosis, the primary accepted therapy for spinal muscular atrophy, and two co-developed therapies to handle a defining pathology of Alzheimer’s illness. Biogen is advancing a pipeline of potential novel therapies throughout neurology, neuropsychiatry, specialised immunology and uncommon illnesses and stays acutely centered on its goal of serving humanity by way of science whereas advancing a more healthy, extra sustainable and equitable world.

The corporate routinely posts data which may be necessary to buyers on its web site at www.biogen.com. Comply with Biogen on social media – Twitter, LinkedIn, Fb, YouTube.

Biogen Secure Harbor
This information launch accommodates forward-looking statements, together with statements made pursuant to the protected harbor provisions of the Non-public Securities Litigation Reform Act of 1995, concerning the potential scientific results of lecanemab; the potential advantages, security and efficacy of lecanemab; potential regulatory discussions, submissions and approvals and the timing thereof; the therapy of Alzheimer’s illness; the anticipated advantages and potential of Biogen’s collaboration preparations with Eisai; the potential of Biogen’s business enterprise and pipeline packages, together with lecanemab; and dangers and uncertainties related to drug improvement and commercialization. These statements could also be recognized by phrases reminiscent of “purpose,” “anticipate,” “imagine,” “might,” “estimate,” “count on,” “forecast,” “intend,” “might,” “plan,” “potential,”” “potential,” “will,” “would” and different phrases and phrases of comparable which means. Drug improvement and commercialization contain a excessive diploma of threat, and solely a small variety of analysis and improvement packages end in commercialization of a product. Ends in early-stage scientific research is probably not indicative of full outcomes or outcomes from later stage or bigger scale scientific research and don’t guarantee regulatory approval. You shouldn’t place undue reliance on these statements or the scientific knowledge offered.

These statements contain dangers and uncertainties that would trigger precise outcomes to vary materially from these mirrored in such statements, together with with out limitation surprising considerations which will come up from further knowledge, evaluation or outcomes obtained throughout scientific research, together with the Readability AD scientific trial and AHEAD 3-45 examine; the incidence of adversarial security occasions; dangers of surprising prices or delays; the danger of different surprising hurdles; regulatory submissions might take longer or be tougher to finish than anticipated; regulatory authorities might require further data or additional research, or might fail or refuse to approve or might delay approval of Biogen’s drug candidates, together with lecanemab; precise timing and content material of submissions to and selections made by the regulatory authorities concerning lecanemab; uncertainty of success within the improvement and potential commercialization of lecanemab; failure to guard and implement Biogen’s knowledge, mental property and different proprietary rights and uncertainties regarding mental property claims and challenges; product legal responsibility claims; third get together collaboration dangers; and the direct and oblique impacts of the continued COVID-19 pandemic on Biogen’s enterprise, outcomes of operations and monetary situation. The foregoing units forth many, however not all, of the components that would trigger precise outcomes to vary from Biogen’s expectations in any forward-looking assertion. Traders ought to contemplate this cautionary assertion in addition to the danger components recognized in Biogen’s most up-to-date annual or quarterly report and in different experiences Biogen has filed with the U.S. Securities and Change Fee. These statements are primarily based on Biogen’s present beliefs and expectations and communicate solely as of the date of this information launch. Biogen doesn’t undertake any obligation to publicly replace any forward-looking statements, whether or not because of new data, future developments or in any other case.

References
¹ Söderberg, L., Johannesson, M., Nygren, P. et al. Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Totally different Types of Amyloid-Beta May Clarify Efficacy and Aspect Results in Medical Trials for Alzheimer’s Illness. Neurotherapeutics (2022). https://doi.org/10.1007/s13311-022-01308-6. Accessed February 9, 2023

SOURCE Eisai Inc.