Consistency of Efficacy Assessments Evaluated Across Various Statistical Methods

 

TOKYO and CAMBRIDGE, Mass., Nov.12, 2021 – Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Michel Vounatsos, “Biogen”) announced today results of sensitivity analyses evaluating the consistency of lecanemab efficacy results across multiple statistical models in patients with Mild Cognitive Impairment (MCI) due to Alzheimer’s disease (AD) and mild AD (collectively known as early AD). This presentation was made by Eisai at the 2021 Clinical Trials on Alzheimer’s Disease (CTAD) conference, November 9-12, 2021 in Boston, Massachusetts and virtually.

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

Study 201, a multicenter, double-blind, placebo-controlled, Phase 2b trial conducted in 856 patients with early AD, evaluated key efficacy assessments, including clinical change on the Alzheimer’s Disease Composite Score (ADCOMS) at the primary endpoint of 12 months and at select key secondary endpoints, Clinical Dementia Rating-Sum-of-Boxes (CDR-SB) and Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14) at 18 months. Six sensitivity analyses across four statistical models (mixed model for repeated measures, disease progression model, natural cubic spline model, and quadratic mixed model) showed consistent positive lecanemab treatment effects for ADCOMS, CDR-SB and ADAS-Cog14 at 18 months.

The primary endpoint was Bayesian analysis of 12-month clinical change on ADCOMS with the goal to identify the most efficacious dose (ED90 dose). Primary analysis was super-superiority over placebo by ≥25%: goal was 80% probability of ≥25% reduction in decline versus placebo. Study achieved the goal of identifying smallest dose that achieved ≥90% of maximum treatment effect (10 mg/kg biweekly), i.e., the ED90 dose. At 12 months, ED90 dose had 64% probability of being super-superior to placebo by 25% reduction. At 12 months, ED90 dose had 98% probability superior to placebo. Consistent treatment effect was observed at 18 months for ADCOMS (29% to 37%), CDR-SB (26.5% to 35%), and ADAS-Cog (47% to 56%), with separation from placebo observed by six months for the top dose (10mg/kg biweekly) across all analyses.

“In Study 201, lecanemab showed robust clearance of brain amyloid and slowing of clinical decline across several clinical and biomarker endpoints. This sensitivity analysis shows lecanemab clinical efficacy results across statistical models are consistent, reliable and further enhances our confidence in the clinical potential of this investigational therapy,” said Michael Irizarry, M.D., Vice President, Deputy Chief Clinical Officer, Neurology Business Group, Eisai Inc. “Through our comprehensive research program, we will continue to advance the understanding of how this anti-amyloid beta protofibril antibody may play a role in the treatment of early and preclinical AD. In March 2021, Eisai completed enrollment of 1,795 patients with early Alzheimer’s disease in our confirmatory Phase 3 Clarity AD clinical study. The Phase 3 clinical study, AHEAD 3-45, is currently exploring lecanemab’s safety and efficacy in individuals with preclinical AD.”

This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that such investigational agent will successfully complete clinical development or gain health authority approval.

 

[Notes to editors]

1.?About Lecanemab (BAN2401)

Lecanemab is an investigational humanized monoclonal antibody for Alzheimer’s disease (AD) that is the result of a strategic research alliance between Eisai and BioArctic. Lecanemab selectively binds to neutralize and eliminate soluble, toxic amyloid-beta (Aβ) aggregates (protofibrils) that are thought to contribute to the neurodegenerative process 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. With regard to the results from pre-specified analysis at 18 months of treatment, Study 201 demonstrated reduction of brain Aβ accumulation (P<0.0001) and slowing of disease progression measured by ADCOMS* (P<0.05) in early AD subjects. The study did not achieve its primary outcome measure** at 12 months of treatment. The Study 201 open-label extension was initiated after completion of the Core period and a Gap period off treatment (average of 24 months) to evaluate safety and efficacy, and is underway.

Eisai obtained the global rights to study, develop, manufacture and market lecanemab for the treatment of AD pursuant to an agreement concluded with BioArctic in December 2007. In March

2014, Eisai and Biogen entered into a joint development and commercialization agreement for lecanemab and the parties amended that agreement in October 2017. Currently, lecanemab is being studied in a pivotal Phase 3 clinical study in symptomatic early AD (Clarity-AD), following the outcome of the Phase 2 clinical study (Study 201). In 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, was initiated. 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 Alzheimer’s Disease and related dementias in the U.S., funded by the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen.

* Developed by Eisai, ADCOMS (AD Composite Score) combines items from the ADAS-Cog (Alzheimer’s Disease Assessment Scale-cognitive subscale), CDR (Clinical Dementia Rating) and the MMSE (Mini-Mental State Examination) scales to enable a sensitive detection of changes in clinical functions of early AD symptoms and changes in memory.

** An 80% or higher estimated probability of demonstrating 25% or greater slowing in clinical decline at 12 months treatment measured by ADCOMS from baseline compared to placebo.

 

2.?About the Collaboration between Eisai and Biogen for Alzheimer’s Disease

Eisai and Biogen are collaborating on the joint development and commercialization of AD treatments. Eisai serves as the lead in the co-development of lecanemab.

 

3.?About the Collaboration between Eisai and BioArctic for Alzheimer’s Disease

Since 2005, BioArctic has had a long-term collaboration with Eisai regarding the development and commercialization of drugs for the treatment of AD. The commercialization agreement on the lecanemab antibody was signed in December 2007, and the development and commercialization agreement on the antibody lecanemab back-up for AD, which was signed in May 2015. Eisai is responsible for the clinical development, application for market approval and commercialization of the products for AD. BioArctic has no development costs for lecanemab in AD.

 

4.?About Eisai Co., Ltd.

Eisai Co., Ltd. is a leading global pharmaceutical company headquartered in Japan. Eisai’s corporate philosophy is based on the human health care (hhc) concept, which is to give first thought to patients and their families, and to increase the benefits that health care provides to them. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realize our hhc philosophy by delivering innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology.

Leveraging the experience gained from the development and marketing of a treatment for Alzheimer’s disease, Eisai aims to establish the “Eisai Dementia Platform.” Through this platform, Eisai plans to deliver novel benefits to those living with dementia and their families through constructing a “Dementia Ecosystem,” by collaborating with partners such as medical organizations, diagnostic development companies, research organizations, and bio-ventures in addition to private insurance agencies, finance industries, fitness clubs, automobile makers, retailers, and care facilities. For more information about Eisai Co., Ltd., please visit https://www.eisai.com.

 

5.?About Eisai Inc.

At Eisai Inc.,?human health care (hhc)?is our goal. We give our first thoughts to patients and their families, and helping to increase the benefits health care provides. As the U.S. pharmaceutical subsidiary of?Tokyo-based Eisai Co., Ltd., we have a passionate commitment to patient care that is the driving force behind our efforts to discover and develop innovative therapies to help address unmet medical needs. Eisai is a fully integrated pharmaceutical business that operates in two global business groups: 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 labs are in Massachusetts?and?Pennsylvania; and our global demand chain organization resides in?Maryland?and?North Carolina. To learn more about Eisai Inc., please visit us at?www.eisai.com/US?and follow us on?Twitter?and?LinkedIn.

 

6.?About Biogen

As pioneers in neuroscience, Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological diseases as well as related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Sir Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today, Biogen has the leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, and is providing the first and only approved treatment to address a defining pathology of Alzheimer’s disease. Biogen is also commercializing biosimilars and focusing on advancing the industry’s most diversified pipeline in neuroscience that will transform the standard of care for patients in several areas of high unmet need.

In 2020, Biogen launched a bold 20-year, $250 million initiative to address the deeply interrelated issues of climate, health, and equity. Healthy Climate, Healthy Lives? aims to eliminate fossil fuels across the company’s operations, build collaborations with renowned institutions to advance the science to improve human health outcomes, and support underserved communities.

The company routinely posts information that may be important to investors on its website at www.biogen.com. To learn more, please visit www.biogen.com and follow Biogen on social media – Twitter, LinkedIn, Facebook, YouTube.

 

7.?Biogen Safe Harbor

This 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 and ADUHELM; potential regulatory discussions, submissions and approvals and the timing thereof; the expected data readout for the Clarity AD study; 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 ADUHELM; 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 trials may not be indicative of full results or results from later stage or larger scale clinical trials 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 trials; 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.

TOKYO and CAMBRIDGE, Mass, Nov. 11, 2021 – Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Michel Vounatsos, “Biogen”) announced today results of new clinical, biomarker and safety assessments of brain amyloid reduction and five-year clinical status of people living with early Alzheimer’s disease (AD) from the lecanemab Phase 2b 201 and the open-label extension (OLE) studies. The findings were presented and discussed in a late-breaking roundtable session with esteemed clinical researchers at the 2021 Clinical Trials on Alzheimer’s Disease (CTAD) conference, November 9-12, 2021, in Boston, Massachusetts and virtually. Eisai recently initiated a rolling submission of a Biologics License Application (BLA) for lecanemab, an investigational anti-amyloid beta (Aβ) protofibril antibody, for the treatment of early AD, to the U.S. Food and Drug Administration (FDA) under the accelerated approval pathway.

 

OLE Study Explores Biomarkers and Clinical Effects Across Five Years

An OLE with 10 mg/kg IV biweekly lecanemab dosing was implemented after analysis of the 18-month, core phase (Study 201, Alz Res Therapy 13;21) with an intervening off-treatment period (gap period) ranging from 9-59 months (mean 24 months). The OLE phase evaluated the effect of lecanemab on amyloid PET over 12 months of treatment, including earlier time points (3 and 6 months) than in the core phase (12 and 18 months). This study design provided the opportunity to explore the biomarker and clinical effects of stopping and restarting lecanemab across five years of disease trajectory.

 

Amyloid Reduction Correlates with Clinical Benefit

The updated assessment of the OLE phase showed that treatment with lecanemab resulted in reduction of brain amyloid levels in as early as 3 months based on OLE data and robust clearance of amyloid plaque with more than 80% of participants (10/12) achieving amyloid negative status by 12-18 months of treatment as measured by PET (visual read). These results are consistent with core phase results. The 201 study core data suggested that clinical efficacy (ADCOMS) is correlated with amyloid reduction (PET SUVr) at both the population (correlation coefficients=0.832, p-value=0.080) and subject levels (correlation coefficients=0.201, slope=0.199, p=0.036). Amyloid PET levels were significantly reduced by quantitative assessment in newly treated OLE subjects in as early as 3 months after initiation of treatment. Additionally, the core data suggested that clinical efficacy is correlated with plasma Aβ at both the population (correlation coefficients=-0.306, not significant) and subject levels (correlation coefficients=-0.208, slope=-3.957, p-value=0.050).

 

Potential Slowing of Cognitive Decline May Suggest Disease-Modifying Effect

The clinical treatment difference in study participants between lecanemab treatment and placebo at the end of core period is maintained after discontinued dosing over the 24-month Gap period. The reduction of clinical decline of participants receiving the highest dose of lecanemab relative to placebo at the end of the 18-month, core period showed a difference of 0.05 in ADCOMS (placebo 0.19, lecanemab 0.14). This treatment difference of 0.10 in subjects who entered OLE was maintained while off-treatment during the gap period up to the beginning of the OLE (placebo 0.28, lecanemab 0.18). Similar findings were observed for CDR-SB and ADAS-Cog, although both groups continued to progress. This pattern of sustained treatment effect after stopping lecanemab, reflected in biomarkers as well amyloid PET, plasma Aβ42/40 and ptau181 is consistent with a disease-modifying effect.

 

Blood Tests May be Able to Monitor Lecanemab Treatment Effects

New results were presented for two new blood tests that were measured in the Phase 2b and OLE studies: Plasma Aβ42/40 ratio and Plasma p-tau181. Plasma Aβ42/40 ratio changes suggested an inverse correlation with amyloid PET changes. Both amyloid PET and blood Aβ show correlation with ADCOMS at the population and individual levels in the core phase (PET correlation coefficients=0.832 population, 0.201 subject level and Aβ plasma correlations coefficients:-0.306 population, -0.208 subject level). Monitoring of treatment effects using plasma biomarkers may allow simple dose modification following robust amyloid removal (e.g., less frequent and/or lower dose).

 

Safety Profile with Low Incidence of ARIA-E and Symptomatic ARIA Rate in Core and OLE

Consistent with the safety findings in the core period, lecanemab was well-tolerated with <10% incidence of ARIA-E at 10 mg/kg biweekly in the Core and OLE. The incidence of symptomatic ARIA-E was <2% in Core and OLE. This safety profile enables lecanemab to be initiated at the therapeutic dose without titration.

“The latest lecanemab findings provide greater insight into the time course and extent of amyloid reduction observed with lecanemab, and the relationship to clinical outcomes and blood-based biomarkers,” said Lynn Kramer, M.D., Chief Clinical Officer, Neurology Business Group, Eisai. “The Clarity AD Phase 3 Study in Early AD, which completed enrollment of 1795 subjects in March, aims to verify these findings.”

The presentation video and slides will be available on the investors’ section of the Eisai Co., Ltd. Website by 10:00 p.m. U.S. EST on November 11.

This release discusses the investigational use of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that such an investigational agent will successfully complete clinical development or gain health authority approval.

Contacts

Eisai Co., Ltd.

MEDIA CONTACT:

Eisai Co., Ltd.

Public Relations Department

TEL: +81-(0)3-3817-5120

Eisai Inc. (U.S.)

Libby Holman

+1-201-753-1945

[email protected]

INVESTOR CONTACT:

Eisai Co., Ltd.

Investor Relations Department

TEL: +81-(0)70-8688-9685

Biogen Inc.

MEDIA CONTACT:

Biogen Inc.

Ashleigh Koss

+1-908-205-2572

[email protected]

INVESTOR CONTACT:

Biogen Inc.

Mike Hencke

+1-781-464-2442

[email protected]

 

[Notes to editors]

1.?About Lecanemab (BAN2401)

Lecanemab is an investigational humanized monoclonal antibody for Alzheimer’s disease (AD) that is the result of a strategic research alliance between Eisai and BioArctic. Lecanemab selectively binds to neutralize and eliminate soluble, toxic amyloid-beta (Aβ) aggregates (protofibrils) that are thought to contribute to the neurodegenerative process 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. With regard to the results from pre-specified analysis at 18 months of treatment, Study 201 demonstrated reduction of brain Aβ accumulation (P<0.0001) and slowing of disease progression measured by ADCOMS* (P<0.05) in early AD subjects. The study did not achieve its primary outcome measure** at 12 months of treatment. The Study 201 open-label extension was initiated after completion of the Core period and a Gap period off treatment of 9-59 months (average of 24 months, n=180 from core study enrolled) to evaluate safety and efficacy, and is underway.

Eisai obtained the global rights to study, develop, manufacture and market lecanemab for the treatment of AD pursuant to an agreement concluded with BioArctic in December 2007. In March 2014 Eisai and Biogen entered into a joint development and commercialization agreement for lecanemab and the parties amended that agreement in October 2017. Currently, lecanemab is being studied in a pivotal Phase 3 clinical study in symptomatic early AD (Clarity-AD), following the outcome of the Phase 2 clinical study (Study 201). In 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, was initiated. 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 Alzheimer’s Disease and related dementias in the U.S, funded by the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen.

* Developed by Eisai, ADCOMS (AD Composite Score) combines items from the ADAS-Cog (Alzheimer’s Disease Assessment Scale-cognitive subscale), CDR (Clinical Dementia Rating) and the MMSE (Mini-Mental State Examination) scales to enable a sensitive detection of changes in clinical functions of early AD symptoms and changes in memory. The ADCOMS scale ranges from a score of 0.00 to 1.97, with higher score indicating greater impairment.

** An 80% or higher estimated probability of demonstrating 25% or greater slowing in clinical decline at 12 months treatment measured by ADCOMS from baseline compared to placebo.

 

2.?About the Collaboration between Eisai and Biogen for Alzheimer’s Disease

Eisai and Biogen are collaborating on the joint development and commercialization of AD treatments. Eisai serves as the lead in the co-development of lecanemab.

 

3.?About the Collaboration between Eisai and BioArctic for Alzheimer’s Disease

Since 2005, BioArctic has had a long-term collaboration with Eisai regarding the development and commercialization of drugs for the treatment of AD. The commercialization agreement on the lecanemab antibody was signed in December 2007, and the development and commercialization agreement on the antibody lecanemab back-up for AD, which was signed in May 2015. Eisai is responsible for the clinical development, application for market approval and commercialization of the products for AD. BioArctic has no development costs for lecanemab in AD.

 

4.?About Eisai Co., Ltd.

Eisai Co., Ltd. is a leading global pharmaceutical company headquartered in Japan. Eisai’s corporate philosophy is based on the human health care (hhc) concept, which is to give first thought to patients and their families, and to increase the benefits that health care provides to them. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realize our hhc philosophy by delivering innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology.

Leveraging the experience gained from the development and marketing of a treatment for Alzheimer’s disease, Eisai aims to establish the “Eisai Dementia Platform.” Through this platform, Eisai plans to deliver novel benefits to those living with dementia and their families through constructing a “Dementia Ecosystem,” by collaborating with partners such as medical organizations, diagnostic development companies, research organizations, and bio-ventures in addition to private insurance agencies, finance industries, fitness clubs, automobile makers, retailers, and care facilities. For more information about Eisai Co., Ltd., please visit https://www.eisai.com.

 

5.?About Eisai Inc.

At Eisai Inc.,?human health care (hhc)?is our goal. We give our first thoughts to patients and their families, and helping to increase the benefits health care provides. As the U.S. pharmaceutical subsidiary of?Tokyo-based Eisai Co., Ltd., we have a passionate commitment to patient care that?is the driving force behind our efforts to discover and develop innovative therapies to help address unmet medical needs. Eisai is a fully integrated pharmaceutical business that operates in two global business groups: 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 labs are in?Massachusetts?and?Pennsylvania; and our global demand chain organization resides in?Maryland?and?North Carolina. To learn more about Eisai Inc., please visit us at?www.eisai.com/US?and follow us on?Twitter?and?LinkedIn.

 

6.?About Biogen

As pioneers in neuroscience, Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological diseases as well as related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Sir Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today, Biogen has the leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, and is providing the first and only approved treatment to address a defining pathology of Alzheimer’s disease. Biogen is also commercializing biosimilars and focusing on advancing the industry’s most diversified pipeline in neuroscience that will transform the standard of care for patients in several areas of high unmet need.

In 2020, Biogen launched a bold 20-year, $250 million initiative to address the deeply interrelated issues of climate, health, and equity. Healthy Climate, Healthy Lives? aims to eliminate fossil fuels across the company’s operations, build collaborations with renowned institutions to advance the science to improve human health outcomes, and support underserved communities.

The company routinely posts information that may be important to investors on its website at?www.biogen.com. To learn more, please visit?www.biogen.com and follow Biogen on social media –?Twitter,?LinkedIn,?Facebook,?YouTube.

 

7.?Biogen Safe Harbor

This 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 and ADUHELM; potential regulatory discussions, submissions and approvals and the timing thereof; the expected data readout for the Clarity AD study; 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 ADUHELM; 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 trials may not be indicative of full results or results from later stage or larger scale clinical trials 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 trials; 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.

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today the presentation of data from the company’s extensive Alzheimer’s disease (AD) pipeline, including six oral presentations that will provide deeper insights into lecanemab’s potential as a treatment for early AD. Eisai initiated a rolling submission of a Biologics License Application (BLA) for lecanemab, an investigational anti-amyloid beta (Aβ) protofibril antibody, for the treatment of early AD, to the U.S. Food and Drug Administration (FDA) under the accelerated approval pathway in September 2021. The lecanemab data and additional research findings from Eisai’s robust AD pipeline will be featured in 10 presentations, including five late breaker oral presentations, at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) conference, November 9-12, 2021, in Boston, Massachusetts and virtually.

“The findings Eisai will present at CTAD provide scientific insights into the potential role of lecanemab in the treatment of early Alzheimer’s disease as well as the relationship between clearance of amyloid-beta plaque from the brain, changes in blood-based biomarkers and clinical outcomes,” said?Michael Irizarry, M.D., Vice President, Deputy Chief Clinical Officer, Neurology Business Group, Eisai Inc. “We are working to advance lecanemab and our other targeted investigational compounds as quickly as possible in our commitment to bringing solutions to patients and their families.”

The focus on AD has historically been on alleviating cognitive, functional, and behavioral symptoms, but there has been significant progress in understanding the biological mechanisms of the disease and Eisai’s investigational pipeline aims to treat the range of underlying pathophysiology, including amyloid, tau and neurodegeneration.

“With lecanemab’s rolling BLA submission to the FDA under the accelerated approval pathway, completion of enrollment of 1,795 patients in the confirmatory Phase 3 Clarity AD clinical trial, initiation of a lecanemab subcutaneous dosing Phase 1 study and the ongoing Phase 3 AHEAD 3-45 study in people with pre-clinical Alzheimer’s disease, it is an exciting time for lecanemab and Eisai’s AD franchise,” said Ivan Cheung, Chairman, Eisai Inc., Senior Vice President, President Neurology Business Group and Global Alzheimer’s Disease Officer, Eisai Co., Ltd. “We are optimistic about the promise lecanemab and other investigational compounds in our robust pipeline may have for people living with Alzheimer’s disease.”

Major Presentations Provide Deeper Scientific Insights into Lecanemab’s Potential as a Treatment for Early AD

· Roundtable: Presentation of the latest lecanemab data, followed by esteemed faculty, Drs. Jeffrey Cummings, Randall Bateman and Christopher van Dyck, facilitating a conversation about the results and insights useful to the broader AD community (Oral Roundtable 5)

· Oral presentation about consistency of efficacy assessments across various statistical methods from the lecanemab Phase II proof-of-concept study (Study 201) in people living with early AD (LB9)

· Oral presentation regarding the introduction of plasma biomarker screening for Phase 3 AHEAD 3-45 study for preclinical AD (LB4)

· Oral presentation outlining the baseline characteristics for the Phase 3 Clarity AD clinical trial for people living with early AD (ROC22)

Positive Opinion Granted for Advanced Renal Cell Carcinoma Based on Significant Progression-Free Survival (PFS), Overall Survival (OS) and Objective Response Rate (ORR) Benefit Compared to Sunitinib in CLEAR/KEYNOTE-581 Trial

Positive Opinion Granted for Advanced Endometrial Carcinoma Based on Significant OS and PFS Benefit Compared to Chemotherapy in Study 309/KEYNOTE-775 Trial

 

TOKYO and KENILWORTH, N.J., Oct. 18, 2021 – Eisai (Headquarters: Tokyo, CEO: Haruo Naito) and Merck & Co., Inc., Kenilworth, N.J., U.S.A. (known as MSD outside the United States and Canada) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted positive opinions recommending approval of the combination of LENVIMA^? (marketed as Kisplyx^? in the European Union [EU] ?for the treatment of advanced renal cell carcinoma [RCC]), the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, plus KEYTRUDA^?, the anti-PD-1 therapy from Merck & Co., Inc., Kenilworth, N.J., U.S.A., for two different indications. One positive opinion is for the first-line treatment of adult patients with advanced RCC, and the other is for the treatment of adult patients with advanced or recurrent endometrial carcinoma (EC) who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and are not candidates for curative surgery or radiation. Decisions on the CHMP’s recommendations will be given by the European Commission for marketing authorization in the EU, and are expected in the fourth quarter of 2021. If approved, this would be the first combination of an anti-PD-1 therapy with a tyrosine kinase inhibitor approved for the treatment of two different types of cancer in the EU.

The positive CHMP opinions are based on data from two pivotal Phase 3 trials: CLEAR (Study 307)/KEYNOTE-581 evaluating the combination in adult patients with advanced RCC and Study 309/KEYNOTE-775 evaluating the combination in certain patients with advanced EC.

In CLEAR/KEYNOTE-581, LENVIMA plus KEYTRUDA demonstrated statistically significant improvements versus sunitinib in the efficacy outcome measures of overall survival (OS), reducing the risk of death by 34% (HR=0.66 [95% CI, 0.49-0.88]; p=0.0049) versus sunitinib, and progression-free survival (PFS), reducing the risk of disease progression or death by 61% (HR=0.39 [95% CI, 0.32-0.49]; p<0.0001) with a median PFS of 23.9 months versus 9.2 months for sunitinib. Additionally, the confirmed objective response rate was 71% (95% CI: 66-76) (n=252) for patients who received LENVIMA plus KEYTRUDA versus 36% with sunitinib (95% CI: 31-41) (n=129).

In Study 309/KEYNOTE-775, LENVIMA plus KEYTRUDA demonstrated statistically significant improvements in the study’s dual efficacy outcome measures of OS, reducing the risk of death by 38% (HR=0.62 [95% CI, 0.51-0.75]; p<0.0001) with a median OS of 18.3 months versus 11.4 months for chemotherapy (investigator’s choice of doxorubicin or paclitaxel), and PFS, reducing the risk of disease progression or death by 44% (HR=0.56 [95% CI, 0.47-0.66]; p<0.0001), with a median PFS of 7.2 months versus 3.8 months for chemotherapy (investigator’s choice of doxorubicin or paclitaxel).

“KEYTRUDA plus LENVIMA demonstrated a survival benefit for advanced renal cell carcinoma in the first-line setting and represents an important potential new treatment option for these patients. Additionally, KEYTRUDA plus LENVIMA is the first anti-PD-1 and tyrosine kinase inhibitor combination to demonstrate a survival benefit in advanced endometrial carcinoma patients, and the benefit was shown regardless of mismatch repair status,” said Dr. Gregory Lubiniecki, Vice President, Clinical Research, Merck & Co., Inc., Kenilworth, N.J., U.S.A. Research Laboratories. “We are pleased that the CHMP has recognized the important role of the combination therapy in these difficult-to-treat cancers.”

“We appreciate the positive opinions rendered by the EU CHMP recommending approval of LENVIMA plus KEYTRUDA in advanced renal cell carcinoma and advanced endometrial carcinoma, underscoring the potential significance of the outcomes observed in the CLEAR/KEYNOTE-581 and Study 309/KEYNOTE-775 trials” said Dr. Takashi Owa, President, Oncology Business Group at Eisai. “We are grateful to the patients who participated in these studies, their families and clinicians. Their commitment made these meaningful milestones possible.”

In CLEAR/KEYNOTE-581, the most common adverse reactions (≥30%) for LENVIMA plus KEYTRUDA* were diarrhoea (61.8%), hypertension (51.5%) fatigue (47.1%), hypothyroidism (45.1%), decreased appetite (42.1%), nausea (39.6%), stomatitis (36.6%), proteinuria (33.0%), dysphonia (32.8%), and arthralgia (32.4%).

In Study 309/KEYNOTE-775, the most common adverse reactions of these patients (≥20%) for LENVIMA plus KEYTRUDA* were hypertension (63%), diarrhoea (57%), hypothyroidism (56%), nausea (51%), decreased appetite (47%), vomiting (39%), fatigue (38%), decreased weight (35%), arthralgia (33%), proteinuria (29%), constipation (27%), headache (27%), urinary tract infection (27%), dysphonia (25%), abdominal pain (23%), asthenia (23%), palmar-plantar erythrodysaesthesia syndrome (23%), stomatitis (23%), anaemia (22%), and hypomagnesaemia (20%).

*According to the information listed in the SmPC (Summaries of Product Characteristics）