Results of the the Phase II Study Demonstrated a Statistcally Significant Difference in Amyloid beta in Brain
TOKYO, Jun 5, 2018 - (ACN Newswire) - Eisai Co., Ltd. (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 (AB) 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, placebocontrolled 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 AB 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 AB 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 AB 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."
About Elenbecestat (generic name, development code: E2609)
Elenbecestat is an oral BACE (beta amyloid cleaving enzyme) inhibitor currently being investigated in Phase III clinical studies for Alzheimer?s disease discovered by Eisai. By inhibiting BACE, a key enzyme in the production of Aβ peptides, elenbecestat reduces Abeta production, which is thought to lead to a reduction in amyloid plaque formations caused by the aggregation of toxic oligomers and protofibrils in the brain. Currently, two global Phase III clinical studies (MISSION AD1/2) of elenbecestat in early Alzheimer?s disease including mild cognitive impairment (MCI) due to AD/Prodromal AD and the early stages of mild AD are underway. In addition, the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the development of elenbecestat, a process allowing priority reviews by the FDA for drugs deemed as having potential to treat serious conditions and tackle key unmet medical needs.
About Study 202 (ClinicalTrials.gov identifier NCT02322021)
Study 202 is a placebo-controlled, double-blind, parallel-group, randomized, dose-finding study to evaluate the safety and tolerability of elenbecestat in 70 patients with mild cognitive impairment due to Alzheimer's disease (prodromal Alzheimer's disease) and mild to moderate dementia due to Alzheimer's disease. The study enrolled patients which met the core clinical research criteria of the U.S. National Institute on Aging - Alzheimer's Association for MCI due to AD or AD dementia, with an MMSE score of 16 or higher and confirmed accumulation of Aβ by PET screening. Patients were allocated to a total of four treatment arms, three for elenbecestat (5 mg/day: 17 patients, 15 mg/day: 19 patients, 50 mg/day: 17 patients) and one for placebo (17 patients). More than half the patients in the elenbecestat 5 mg and 15 mg treatment arms had their dose increased to 50 mg/day during the 18 month treatment period. Mean duration of 50 mg total arm on 50 mg/day was 11 months. The primary objectives are safety and tolerability at 18 months. Major exploratory endpoints are the change in accumulation of Abeta as measured by amyloid PET (35 patients) and the change in dementia assessment scales including CDR-SB and ADCOMS (41 patients), at 18 months compared to baseline.
Eisai Co., Ltd. (TSE:4523; ADR:ESALY) is a research-based human health care (hhc) company that discovers, develops and markets products throughout the world. Eisai focuses its efforts in three therapeutic areas: integrative neuroscience, including neurology and psychiatric medicines; integrative oncology, which encompasses oncotherapy and supportive-care treatments; and vascular/immunological reaction. Through a global network of research facilities, manufacturing sites and marketing subsidiaries, Eisai actively participates in all aspects of the worldwide healthcare system. For more information about Eisai Co., Ltd., please visit www.eisai.com.
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