Eisai Presents New Analyses from Phase IIb Study of Lecanemab at CTAD Confirming Consistent Clinical Benefits in Early Alzheimer’s Disease

Tokyo, December 6, 2021 /PRNewswire/ -- Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, hereinafter "Eisai") and Biogen Inc. (Nasdaq: BIIB, Headquarters: Cambridge, Massachusetts, CEO: Michel Vounatsos, hereinafter "Biogen") announced the results of a sensitivity analysis evaluating the consistency of Lecanemab's efficacy outcomes using multiple statistical models in patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and mild AD (collectively referred to as early AD). Eisai presented this research at the 2021 Clinical Trials on Alzheimer's Disease (CTAD) conference held in Boston, Massachusetts, from November 9 to 12, 2021.

In September 2021, Eisai initiated a rolling submission of the Biologics License Application (BLA) for Lecanemab (an investigational anti-amyloid beta protofibril antibody) to the U.S. Food and Drug Administration (FDA) through the accelerated approval pathway for the treatment of early AD.

Study 201 was a multicenter, double-blind, placebo-controlled, Phase IIb trial conducted in 856 patients with early AD. The trial evaluated key efficacy assessments, including the primary endpoint of the Alzheimer's Disease Composite Score (ADCOMS) at 12 months and selected key secondary endpoints of clinical change at 18 months in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) and the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14). Six sensitivity analyses using four statistical models (mixed model for repeated measures, disease progression model, natural cubic spline model, and quadratic mixed model) showed consistent treatment effects of Lecanemab on ADCOMS, CDR-SB, and ADAS-Cog14 at 18 months.

The primary endpoint was a Bayesian analysis of ADCOMS for 12-month clinical change, aimed at determining the most effective dose (ED90 dose). The main analysis focused on the probability of significantly slowing clinical decline by more than 25% compared to placebo: the goal was an 80% likelihood of slowing clinical decline by ≥25% versus placebo. The study achieved its objective of identifying the minimum dose (10 mg/kg every two weeks) that achieves ≥90% of the optimal therapeutic effect, i.e., the ED90 dose. At 12 months, the ED90 dose had a 64% probability of slowing clinical decline by 25%, showing significant superiority over placebo. The probability of the ED90 dose being superior to placebo was 98% at 12 months. Across all analyses, consistent treatment effects were observed at 18 months for ADCOMS (29%-37%), CDR-SB (26.5%-35%), and ADAS-Cog (47%-56%), with differences between the highest dose (10 mg/kg every two weeks) and placebo detected as early as 6 months.

"In Study 201, multiple clinical and biomarker endpoints demonstrated that Lecanemab robustly clears amyloid-beta from the brain and slows clinical decline. This sensitivity analysis shows that across statistical models, the clinical efficacy outcomes of Lecanemab are consistent and reliable, further strengthening our confidence in the clinical potential of this investigational treatment," said Dr. Michael Irizarry, Vice President and Deputy Chief Clinical Officer of the Neurology Business Group at Eisai. "Through our comprehensive research program, we will continue to deepen our understanding of how this anti-amyloid-beta protofibril antibody works in the treatment of early and preclinical Alzheimer’s disease (AD). In March 2021, Eisai completed enrollment of 1,795 patients with early Alzheimer's disease in our confirmatory Phase III Clarity AD clinical study. The Phase III clinical study (AHEAD 3-45) is currently exploring the safety and efficacy of Lecanemab in individuals with preclinical AD."

This press release discusses the experimental use of the drug under development and does not intend to convey conclusions about its efficacy or safety. There is no guarantee that such an experimental drug will successfully complete clinical development or gain approval from health authorities.

[Editor's Note]

1.AboutLecanemab（BAN2401）

Lecanemab is an investigational humanized monoclonal antibody intended for the treatment of Alzheimer's disease (AD), developed through a collaboration between Eisai and BioArctic. Lecanemab selectively binds, neutralizes, and eliminates soluble, toxic β-amyloid (Aβ) aggregates (protofibrils), which are believed to accelerate neurodegeneration in AD. Thus, Lecanemab may impact the disease's pathological mechanisms and slow its progression. Regarding the pre-specified analysis results at 18 months of treatment, Study 201 demonstrated a reduction in brain Aβ accumulation (P<0.0001) and a slowing of disease progression as measured by ADCOMS* (P<0.05) in early AD subjects. The study did not meet its primary endpoint** at 12 months of treatment. Following the core phase and a treatment gap period (average 24 months), an open-label extension of Study 201 was initiated to evaluate safety and efficacy, which is currently ongoing.

According to the agreement signed with BioArctic in December 2007, Eisai obtained global rights for the research, development, manufacturing, and marketing of Lecanemab for the treatment of AD. In March 2014, Eisai and Biogen entered into a co-development and commercialization agreement for Lecanemab, which was revised by both parties in October 2017. Currently, based on the results of the Phase II clinical study (Study 201), a pivotal Phase III clinical study (Clarity-AD) of Lecanemab for symptomatic early AD is ongoing. In July 2020, a Phase III clinical study (AHEAD 3-45) was initiated for preclinical AD individuals (these patients are clinically normal but have moderate or elevated levels of amyloid in the brain). The AHEAD 3-45 study is conducted through a public-private partnership model between the Alzheimer's Clinical Trials Consortium (funded by the National Institute on Aging, a division of the U.S. National Institutes of Health, providing infrastructure for academic clinical trials for Alzheimer’s disease and related dementias in the U.S.) and Eisai and Biogen.

*ADCOMS (AD Composite Score) developed by Eisai combines items from the ADAS-Cog (Alzheimer's Disease Assessment Scale-Cognitive Subscale), CDR (Clinical Dementia Rating), and MMSE (Mini-Mental State Examination) scales to sensitively detect clinical functional and memory changes associated with early AD symptoms.

**Compared with placebo, the estimated probability of slowing clinical decline from baseline by ≥25% as measured by ADCOMS at 12 months of treatment is ≥80%.

2.Eisai and Biogen's Collaboration in Alzheimer's Disease

Eisai and Biogen have collaborated on the development and commercialization of AD treatment drugs. Eisai is the lead developer of Lecanemab.

3.Eisai andBioArcticCollaboration in Alzheimer's Disease

Since 2005, BioArctic has established a long-term collaboration with Eisai for the development and commercialization of treatments for Alzheimer's disease (AD). In December 2007, a commercial agreement was signed for the antibody Lecanemab. In May 2015, another agreement was reached for the development and commercialization of a backup AD antibody for Lecanemab. Eisai is responsible for the clinical development, regulatory submissions, and commercialization of AD products. BioArctic does not bear the development costs of Lecanemab for AD.

4.About Eisai Co., Ltd.

Eisai Co., Ltd. is a leading global pharmaceutical company headquartered in Japan. The corporate philosophy of Eisai Co., Ltd. is based onConcern for Human Health (hhc）Philosophy: Always putting the interests of patients and their families first, and contributing to their well-being. With a global network of research institutions, production bases, and marketing subsidiaries, the company is committed to providing innovative products targeting unmet medical needs, with a particular focus on strategic areas such as neurology and oncology.hhcConcept.

Eisai Plans to Leverage Experience Gained from the Development and Launch of Alzheimer's Disease Treatment Drugs to Establish the "Eisai Dementia Platform." Through this platform, Eisai aims to build a "Dementia Ecosystem" by collaborating with partners such as medical institutions, diagnostic development companies, research organizations, biotech venture firms, private insurance agencies, financial institutions, fitness clubs, automobile manufacturers, retailers, and care facilities. The goal is to bring new benefits to dementia patients and their families. For more information about Eisai Co., Ltd., please visithttps://www.eisai.com。

5.About Eisai USA

At Eisai Co., Ltd.,Concern for Human Health (hhc）is our goal. We prioritize the interests of patients and their families, contributing to the enhancement of their well-being. As the U.S. subsidiary of Eisai Co., Ltd., headquartered in Tokyo, our passion for patient care drives us to strive for the discovery and development of innovative therapies to help address unmet medical needs. Eisai is a fully integrated pharmaceutical company with operations in two global business areas: oncology and neurology (dementia-related diseases and neurodegenerative diseases). Our U.S. headquarters, commercial and clinical development organizations are located in New Jersey; our discovery laboratories are in Massachusetts and Pennsylvania; and our global demand chain organizations are in Maryland and North Carolina. For more information about Eisai, please visitwww.eisai.com/US, and follow usTwitterAndLinkedInAccount.

6.About Biogen

As a pioneer in neuroscience, Biogen discovers, develops, and delivers innovative therapies for patients worldwide who are affected by serious neurological diseases. Founded in 1978 by Charles Weissmann, Heinz Schaller, Sir Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp, Biogen was one of the world’s first biotechnology companies. Today, Biogen has a leading portfolio of treatments for multiple sclerosis, introduced the first approved therapy for spinal muscular atrophy, and is providing the first and only treatment approved to address the underlying pathology of Alzheimer’s disease. Biogen is also commercializing biosimilars and is committed to advancing the most diversified pipeline in the neuroscience industry, which will transform standard care for patients in several areas with high unmet medical needs.

In 2020, Biogen launched a bold 20-year, $250 million initiative aimed at addressing the closely interconnected issues of climate, health, and equity. Healthy Climate, Healthy Lives™ aims to eliminate fossil fuels from the company’s operations and establish partnerships with renowned institutions to advance scientific progress, improve human health outcomes, and provide support to underserved communities.

The company frequently on its websitewww.biogen.comPublish information that may be important to investors. For more information, please visitwww.biogen.com, and on social media -Twitter、LinkedIn、Facebook、YouTubeFollow Biogen's account.

7.Biogen Safe Harbor

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 regarding the potential clinical efficacy of Lecanemab; the potential benefits, safety, and efficacy of Lecanemab and ADUHELM; potential regulatory discussions, submissions, and approvals and their timing; anticipated data readouts from the Clarity AD study; the treatment of Alzheimer's disease; the expected benefits and potential of the collaboration between Biogen and Eisai; the potential of Biogen’s commercial business and R&D programs, including Lecanemab and ADUHELM; and statements regarding risks and uncertainties associated with drug development and commercialization. These forward-looking statements can be identified by words such as "aim," "anticipate," "believe," "can," "estimate," "expect," "forecast," "intend," "may," "plan," "might," "potential," "will," and other words of similar meaning.

Drug development and commercialization involve high risks, and only a small number of R&D projects will ultimately succeed in achieving product commercialization. Results from early clinical trials may not represent the full or individual results of later or larger-scale clinical trials, nor can they guarantee that a drug will receive regulatory approval. You should not place excessive reliance on these statements or the published scientific data.

These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including but not limited to: unexpected concerns that may arise from additional data, analysis or results obtained during clinical trials; the occurrence of adverse safety events; risks related to unexpected costs or delays; the risk of other unexpected obstacles; submissions to regulatory authorities potentially taking longer or being more difficult to complete than expected; regulatory authorities possibly requiring additional information or further studies, or potentially failing or refusing to approve, or delaying the approval of, Biogen’s investigational drugs (including Lecanemab); the timing and content of submissions to regulatory authorities and regulatory decisions relating to Lecanemab; the 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, operating results and financial condition. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from any forward-looking statement made by Biogen. 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 forward-looking statements are based on Biogen’s current beliefs and expectations and speak only as of the date of this press release.

Biogen has no obligation to publicly update any forward-looking statements, whether such updates are based on new information, future developments, or any other reason.