ADUHELM™ Demonstrates Positive Correlation Between Biomarker Response and Slowed Clinical Decline in Alzheimer’s Disease

December 2021, Tokyo, JapanDay 8/PR Newswire/ --November 12, 2021,Biogen(Nasdaq: BIIB) and Eisai Co., Ltd. (Tokyo, Japan) announced that data from approximately 7,000 plasma samples from more than 1,800 patients in the Phase III clinical trial of ADUHELM™ (aducanumab-avwa) showed a statistically significant correlation between reduced plasma p-tau and slowed cognitive and functional decline in Alzheimer's disease. The reduction in plasma p-tau181 was also associated with decreased amyloid-beta plaques. Pre-specified analyses were conducted by an independent laboratory on plasma samples drawn from the two pivotal ADUHELM Phase III EMERGE and ENGAGE trials. These findings were presented at the Clinical Trials on Alzheimer's Disease (CTAD) conference held in Boston, Massachusetts, from November 9-12.

The analysis highlights that, as measured by plasma p-tau181, ADUHELM significantly reduces tau pathology, a defining characteristic of Alzheimer's disease, compared to placebo. The higher the dose and longer the duration of ADUHELM treatment, the more pronounced the effect. In patients treated with ADUHELM, a significant reduction in plasma p-tau181 was also statistically significantly associated with a slowing of cognitive and functional decline. Additionally, the analysis indicates a statistically significant correlation between changes in plasma p-tau181 and reductions in amyloid-beta plaques, suggesting that ADUHELM impacts both core pathological features of Alzheimer's disease.

Alfred Sandrock, Jr., Ph.D., Head of Research and Development at Biogen, stated: "We have robust and consistent data showing that ADUHELM can impact the two well-established core pathological features of Alzheimer's disease, and there is substantial evidence indicating a therapeutic correlation between changes in plasma p-tau181 and slowing disease progression. We are committed to continuing to generate data, and we believe these new findings will help guide treatment decisions and advance Alzheimer's disease research, including diagnosis and disease monitoring."。”

The results showed that, in two Phase III trials, ADUHELM significantly reduced plasma p-tau181 in a dose- and time-dependent manner compared to placebo. In the EMERGE high-dose group, p-tau decreased by 13% from baseline (p<0.001), while in the placebo group, p-tau increased by 8% from baseline; in the ENGAGE high-dose group, p-tau decreased by 16% from baseline (p<0.001), while in the placebo group, p-tau increased by 9% from baseline.

In all four clinical outcome measures of the Phase III trial, a significant reduction in plasma p-tau181 was associated with a slowing of clinical decline. The correlation values for these endpoints in EMERGE and ENGAGE were as follows: Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores were R=0.11 (p=0.0166) and R=0.14 (p=0.0005), respectively; Mini-Mental State Examination (MMSE) scores were R=-0.21 (p<0.0001) and R=-0.15 (p=0.0002); Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 13) scores were R=0.17 (p=0.0001) and R=0.15 (p=0.0002); and Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale-Mild Cognitive Impairment version (ADC-ADL-MCI) scores were R=-0.12 (p=0.0086) and R=-0.14 (p=0.0010).

Changes in plasma p-tau181 were also significantly correlated with changes in amyloid β positron emission tomography (PET) standardized uptake value ratio (SUVR): EMERGE: R=0.38, p<0.0001; ENGAGE: R=0.42, p<0.0001.

Dr. Oskar Hansson, Professor of Neurology at Lund University in Sweden and Skåne University Hospital (who led the oral late-breaking presentation at the CTAD conference), stated: "These data not only demonstrate an important link between ADUHELM's ability to clear amyloid-beta plaques and reduce plasma p-tau levels, but also indicate that these reductions are significantly associated with slowing cognitive decline. The studies involving nearly 2,000 patients provide valuable insights into the interconnected pathodynamic mechanisms of this complex disease."

The two pathological hallmarks of Alzheimer's disease — amyloid-beta plaques and neurofibrillary tangles (composed of abnormal p-tau) — disrupt communication between neurons, leading to loss of brain function, neurodegeneration, and clinical decline, all of which can begin to appear in the early stages of Alzheimer's disease.

Biogen also provided data from the Phase IIIb re-dosing study EMBARK, which examined the effects of a prolonged suspension of ADUHELM treatment (average duration of 1.7 years) in Alzheimer's disease patients before restarting therapy. The study showed that the reduction in amyloid-beta plaques was maintained in the high-dose group compared to the placebo group during the treatment interval. Although disease progression continued after discontinuation of treatment, the numerical differences in various clinical endpoints supporting ADUHELM were still preserved.

EMBARK Baseline Data Highlights the Need for Further Scientific Evidence to Better Understand the Impact of Discontinuing Anti-Amyloid Treatment and the Potential Role of Other Pathological Processes in Disease Progression.

EMBARK is not a randomized study, so there may be selection bias in the enrollment of patients; when interpreting these data, it is necessary to weigh the potential impact of inter-individual heterogeneity in dose, duration of exposure, and treatment intervals within the study. This analysis comes from the largest existing clinical trial dataset for early Alzheimer's disease, which includes 1,856 screened patients from EMERGE, ENGAGE, PRIME, and EVOLVE.

AboutADUHELM™（aducanumab-avwa) Injection100 mg/mL

ADUHELM is indicated for the treatment of Alzheimer's disease. ADUHELM treatment should be initiated in patients with mild cognitive impairment or mild dementia stage of the disease (the population in whom treatment was initiated in clinical trials). There are no safety or efficacy data available on initiating treatment earlier or later than the studied disease stages. This indication received accelerated approval based on the observed reduction in amyloid beta plaques in patients treated with ADUHELM. The final confirmation of this indication will depend on the verification of clinical benefit in confirmatory clinical trials.

Aducanumab-avwa is a monoclonal antibody targeting amyloid beta. The accumulation of amyloid beta plaques in the brain is a definitive pathophysiological characteristic of Alzheimer's disease. The accelerated approval of ADUHELM is based on clinical trial data, which showed that ADUHELM can reduce amyloid beta plaques (a surrogate biomarker reasonably likely to predict clinical benefit), thereby slowing clinical decline.

ADUHELM can cause serious side effects, including: Amyloid-related imaging abnormalities or "ARIA." ARIA is a common side effect that usually does not cause any symptoms but can be severe. While most people do not experience symptoms, some may have headache, confusion, dizziness, vision changes, and nausea. The patient's healthcare provider will perform magnetic resonance imaging (MRI) scans before and during ADUHELM treatment to check for ARIA. ADUHELM can also cause serious allergic reactions. The most common side effects of ADUHELM include: brain swelling, with or without small spots of bleeding in or on the surface of the brain (ARIA); headache; and falls. Patients should call their healthcare provider for medical advice about side effects.

Since October 2017, Biogen and Eisai Co., Ltd. have been collaborating globally to jointly develop and promote Aducanumab.

Please click here to get ADUHELMFull Prescribing Information, includingMedication Guide。

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 treatment for spinal muscular atrophy, and is providing the first and only approved treatment targeting 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 is set to transform standard care for patients across 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.

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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）The concept is to put the interests of patients and their families first, contributing to the enhancement of their well-being. The company, with its global network of research institutions, production bases, and marketing subsidiaries, 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" in collaboration 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。

Biogen Safety 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 ADUHELM; the potential benefits, safety, and effectiveness of ADUHELM; the treatment of Alzheimer's disease; the results of the EMBARK study; the expected benefits and potential of Biogen's collaboration with Eisai; clinical development plans, clinical trials, and data interpretation and publication; and statements related to 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 similar words. Drug development and commercialization involve high risks, and only a small number of research and development projects will ultimately succeed in achieving product commercialization. Results from early-stage clinical trials may not represent the full results or all results of later-stage or larger-scale clinical trials, nor can they guarantee that the drug will receive regulatory approval. You should not place undue 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; risks related to other unexpected obstacles; failure to protect and enforce Biogen’s data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; risks related to current and potential future healthcare reforms; 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 materially from what Biogen expects 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 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 as a result of new information, future developments or otherwise.