°®¶¹´«Ã½

°®¶¹´«Ã½. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and Biogen Inc. (NASDAQ: BIIB) (Headquarters: Cambridge, Massachusetts, United States, CEO: Michel Vounatsos, “Biogen”) announced today that elenbecestat was generally safe and well tolerated in a Phase II clinical study (Study 202) of the oral BACE (beta amyloid cleaving enzyme) inhibitor elenbecestat (development code: E2609) conducted in the United States, and the results demonstrated a statistically significant difference in amyloid beta (Aβ) levels in the brain measured by amyloid-PET (positron emission tomography). A numerical slowing of decline in functional clinical scales of a potentially clinically important difference was also observed, although this effect was not statistically significant. This study, a Phase II study of 70 patients, is the first study of a BACE inhibitor to show a statistically significant difference in amyloid beta in the brain while also suggesting a delay of clinical symptom decline in exploratory endpoints.

Study 202 (ClinicalTrials.gov identifier NCT02322021) is a multicenter, randomized, double-blind, placebo-controlled parallel-group 18-month Phase II clinical study in patients with mild cognitive impairment (MCI) due to Alzheimer’s disease, or mild to moderate dementia due to Alzheimer’s disease with confirmed amyloid pathology by PET screening. Seventy patients were randomized to four treatment arms receiving elenbecestat (5, 15, or 50 mg) or placebo daily. During the study period, more than half the patients in the elenbecestat 5 mg and 15 mg arms were switched to the 50 mg arm for three months or more. The 50 mg treatment arm plus the group switched to the 50 mg arm are hereafter referred to as “50 mg total arm” (38 subjects) with a mean duration of approximately 11 months on 50 mg per day.

Elenbecestat demonstrated acceptable safety and tolerability profile through 18 months of study drug administration. In the elenbecestat 50 mg total arm, the six most common adverse events observed were contact dermatitis, upper respiratory infection, headache, diarrhea, fall, and dermatitis. No serious adverse reactions suggestive of hepatic toxicity were observed in this study.

In addition to the safety objectives, the study assessed Aβ in the brain at 18 months as measured by amyloid PET as well as efficacy in terms of clinical symptoms, which were exploratory objectives in this study.
The elenbecestat 50 mg total arm demonstrated a statistically significant difference in Aβ levels in the brain as measured by amyloid PET compared with placebo (35 subjects participated in this longitudinal amyloid PET assessment). This is the first time in which a significant effect in Aβ in the brain using a BACE inhibitor was confirmed in a clinical study of patients with mild cognitive impairment (MCI) through moderate Alzheimer’s dementia.

CDR-SB (Clinical Dementia Rating Sum of Boxes) was an exploratory endpoint to assess efficacy in terms of clinical symptoms. The study showed numerically less decline in CDR-SB for the elenbecestat 50 mg total arm as compared to placebo of a potentially clinically important difference (41 subjects participated in this assessment), which was not statistically significant. Further, a similar magnitude and direction of differential in decline was observed in a post-hoc analysis of ADCOMS, Eisai’s newly developed assessment scale (Alzheimer’s Disease Composite Score) in the elenbecestat 50 mg total arm as compared to placebo. The study was not powered to show statistical significance compared to placebo on clinical symptoms.

Eisai plans to present detailed results of the study at a future medical meeting.

Elenbecestat, discovered by Eisai, has been jointly developed by Eisai and Biogen since March 2014. The two companies are currently conducting two global Phase III clinical studies (MISSION AD1/2) in early Alzheimer’s disease.

“It is highly encouraging that Study 202 confirmed elenbecestat’s treatment effect in reducing amyloid in the brain and suggested a slowing of clinical decline. Eisai and Biogen will continue to work together to advance the ongoing Phase III program (MISSION AD) in order to contribute a new potential treatment option to Alzheimer’s disease patients as soon as possible,” said Lynn Kramer, MD, Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai.

“Biogen is heartened by the safety and tolerability results of this study of elenbecestat,” said Alfred Sandrock, M.D., Ph.D., executive vice president and chief medical officer at Biogen.  “We remain committed to research in Alzheimer’s, an area of significant unmet need with a devastating impact on those living with the disease, their families, friends, and society.”

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, including statements about results from the Phase II study of elenbecestat, the potential effects of elenbecestat, Biogen’s strategy and plans, and the potential of Biogen’s commercial business and pipeline programs. These forward-looking statements may be accompanied by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “except,” “forecast,” “intend,” “may,” “plan,” “potential,” “possible,” “will,” 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: the risk that we may not fully enroll our clinical trials or enrollment will take longer than expected, unexpected concerns may arise from additional data, analysis, or results obtained during our clinical trials, 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, the occurrence of adverse safety events, we may encounter other unexpected hurdles, which may be impacted by, among other things, the occurrence of adverse safety events, failure to obtain regulatory approvals in certain jurisdictions, or failure to protect intellectual property and other proprietary rights, or uncertainty of success in the development and potential commercialization of elenbecestat. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our 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 press 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.