¡¤ ALL KEY SECONDARY ENDPOINTS ALSO MET, DEMONSTRATING HIGHLY STATISTICALLY SIGNIFICANT RESULTS

¡¤ PROFILE OF AMYLOID-RELATED IMAGING ABNORMALITIES (ARIA) INCIDENCE WAS WITHIN EXPECTATIONS

¡¤ EISAI AIMS TO FILE FOR TRADITIONAL APPROVAL IN THE U.S., AND TO SUBMIT MARKETING AUTHORIZATION APPLICATIONS IN JAPAN AND EUROPE BY THE END OF EISAI FY2022, WHICH ENDS ON MARCH 31, 2023

 

TOKYO and CAMBRIDGE, Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Michel Vounatsos, “Biogen”) announced positive topline results from Eisai¡¯s large global Phase 3 confirmatory Clarity AD clinical trial of lecanemab (development code: BAN2401), an investigational anti-amyloid beta (A¦Â) protofibril antibody for the treatment of mild cognitive impairment (MCI) due to Alzheimer¡¯s disease (AD) and mild AD (collectively known as early AD) with confirmed presence of amyloid pathology in the brain. Lecanemab met the primary endpoint (CDR-SB: Clinical Dementia Rating-Sum of Boxes*) and all key secondary endpoints with highly statistically significant results. Eisai will discuss this data with regulatory authorities in the U.S., Japan and Europe with the aim to file for traditional approval in the US and for marketing authorization applications in Japan and Europe by the end of Eisai¡¯s FY2022, which ends March 31, 2023. Additionally, Eisai will present the Clarity AD study results on November 29, 2022, at the Clinical Trials on Alzheimer¡¯s Congress (CTAD), and publish the findings in a peer-reviewed medical journal.

 

* CDR-SB is a numeric scale used to quantify the various severity of symptoms of dementia. Based on interviews of people living with AD and family/caregivers, qualified healthcare professionals assess cognitive and functional performance in six areas: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. The total score of the six areas is the score of CDR-SB, and CDR-SB is also used as an appropriate item for evaluating the effectiveness of therapeutic drugs targeting the early stages of AD.

 

Lecanemab treatment met the primary endpoint and reduced clinical decline on the global cognitive and functional scale, CDR-SB, compared with placebo at 18 months by 27%, which represents a treatment difference in the score change of -0.45 (p=0.00005) in the analysis of Intent-to-treat (ITT) population. Starting as early as six months, across all time points, the treatment showed highly statistically significant changes in CDR-SB from baseline compared to placebo (all p-values are less than 0.01). All key secondary endpoints were also met with highly statistically significant results compared with placebo (p<0.01). Key secondary endpoints were the change from baseline at 18 months compared with placebo of treatment in amyloid levels in the brain measured by amyloid?positron emission tomography (PET), the AD Assessment Scale-cognitive subscale14 (ADAS-cog14), AD Composite Score (ADCOMS) and the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL).

 

The incidence of amyloid-related imaging abnormalities-edema/effusion (ARIA-E), an adverse event associated with anti-amyloid antibodies, was 12.5% in the lecanemab group and 1.7% in the placebo group. The incidence of symptomatic ARIA-E was 2.8% in the lecanemab group and 0.0% in the placebo group. The ARIA-H (ARIA cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis) rate was 17.0% in the lecanemab group and 8.7% in the placebo group. The incidence of symptomatic ARIA-H was 0.7% in the lecanemab group and 0.2% in the placebo group. There was no imbalance in isolated ARIA-H (i.e., ARIA-H in patients who did not also experience ARIA-E) between lecanemab (8.8%) and placebo (7.6%). The total incidence of ARIA (ARIA-E and/or ARIA-H) was 21.3% in the lecanemab group and 9.3% in the placebo group. Overall, lecanemab¡¯s ARIA incidence profile was within expectations.

 

Clarity AD was a global confirmatory Phase 3 placebo-controlled, double-blind, parallel-group, randomized study in 1,795 people with early AD. The treatment group was administered a dosage of 10 mg/kg bi-weekly of lecanemab, with participants allocated in a 1:1 ratio to receive either placebo or lecanemab. The baseline characteristics of both placebo and lecanemab groups are similar and well balanced.?Eligibility criteria allowed patients with a broad range of comorbidities/comedications: hypertension, diabetes, heart disease, obesity, renal disease and anti-coagulants, etc. Eisai¡¯s recruitment strategy for the Clarity AD clinical trial ensured greater inclusion of ethnic and racial populations in the U.S., resulting in approximately 25% of the total U.S. enrollment including Hispanic and African American persons living with early AD. Due to the inclusive eligibility criteria and the successful recruitment of diverse ethnic and racial populations in the U.S., Clarity AD¡¯s population is generally comparable to the country¡¯s Medicare population.

 

¡°Since Eisai launched Aricept in the U.S. and Japan in the late 1990s and obtained its approval in over 100 countries, Eisai has provided the drug to people living with dementia while building empathy for them and their families through disease education efforts and community involvement. The positive result of the lecanemab, an anti-A¦Â protofibril antibody, pivotal study after almost 25 years since Aricept¡¯s launch is an important milestone for Eisai in fulfilling our mission to meet the expectations of the Alzheimer¡¯s disease community. Alzheimer¡¯s disease not only presents a great challenge for patients and their families, but it also negatively impacts society, including decreased productivity, increased social costs and disease-related anxiety. We believe that helping to alleviate these burdens will positively impact society as a whole,¡± said Haruo Naito, Chief Executive Officer at Eisai. ¡°Additionally, the lecanemab Clarity AD study results prove the amyloid hypothesis, in which the abnormal accumulation of A¦Â in the brain is one of the main causes of Alzheimer¡¯s disease, when targeted with a protofibril-binding therapy. Eisai believes these findings will create new horizons in the diagnosis and treatment of Alzheimer¡¯s disease as well as further activate innovation for new treatment options. The successful results of the Clarity AD clinical trial would not be possible without the truly inspiring dedication of the study¡¯s participants, their families and caregivers and the clinical investigators around the world. We thank all the people involved in the study for their invaluable contributions.¡±

 

¡°Today¡¯s announcement gives patients and their families hope that lecanemab, if approved, can potentially slow the progression of Alzheimer¡¯s disease, and provide a clinically meaningful impact on cognition and function,¡± said Michel Vounatsos, Chief Executive Officer at Biogen. ¡°Importantly, the study shows that removal of aggregated amyloid beta in the brain is associated with a slowing of disease in patients at the early stage of the disease. We want to thank the many patients who participated in this groundbreaking global study and want to acknowledge the clinical investigators who worked tirelessly to increase the enrollment of traditionally underrepresented populations. As pioneers in neuroscience, we believe defeating this disease will require multiple approaches and treatment options, and we look forward to continuing the discussion about the significance of these findings with the patient, scientific, and medical communities.¡±

 

In July 2022, the U.S. Food and Drug Administration (FDA) accepted Eisai¡¯s Biologics License Application (BLA) for lecanemab under the accelerated approval pathway and granted Priority Review. The Prescription Drugs User Fee Act action date (PDUFA) is set for January 6, 2023. The FDA has agreed that the results of Clarity AD can serve as the confirmatory study to verify the clinical benefit of lecanemab. In an effort to secure traditional FDA approval for lecanemab as soon as possible, Eisai submitted the BLA through the FDA¡¯s Accelerated Approval Pathway so that the agency could complete its review of all lecanemab data with the exception of the data from the confirmatory Clarity AD study.

 

In March 2022, Eisai began submitting application data, with the exception of Clarity AD data, to Japan¡¯s Pharmaceuticals and Medical Devices Agency (PMDA) under the prior assessment consultation system with the aim of obtaining early approval for lecanemab so that people living with early AD may have access to the therapy as soon as possible.

 

Eisai serves as the lead of lecanemab development and regulatory submissions globally with both Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority.