Eisai Co.,Ltd.(Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced the presentation and discussion about the treatment, including oral beta amyloid cleaving enzyme (BACE) inhibitor elenbecestat* research data on Alzheimer’s disease (AD), were given in the AAIC’s Focused Topic Session “Discussion of BACEi Trial Findings: Challenges and Opportunities” at the Alzheimer’s Association International Conference (AAIC) held in Los Angeles, California, United States, from July 14 to 18, 2019. In addition, Eisai held a symposium focused on the rationale and opportunities for drug development for pre-clinical AD.
1. AAIC’s Focused Topic Session (Discussion of BACEi Trial Findings: Challenges and Opportunities)
In this session, each company presented information about their own BACE inhibitors. Eisai gave a comprehensive presentation about the findings from the following nonclinical and clinical studies, as well as the clinical study status in regard to elenbecestat.
- The nonclinical study results did not show significant effects on the decrease in spinal density and the impairment of mitochondrial function, relating to the cognitive function deterioration, at dose with significant decline of amyloid beta (Aβ) level in CSF, as an effect of elenbecestat.
- The safety data, including the change in cognitive function in 900 patients with treatment administration for 6 months or more, has been reviewed periodically by the Data Safety Monitoring Board (DSMB). In its most recent review the DSMB recommended the continuation of the elenbecestat Phase 3 MISSION AD 1 and 2 studies without modification.
- In the clinical phase II study (Study 202), patients with mild cognitive impairment (MCI) due to AD, or mild-to-moderate dementia due to AD with confirmed amyloid pathology by positron emission tomography (PET) who were administered elenbecestat 50mg showed a significant reduction in brain amyloid load at 18 months versus the placebo group with amyloid PET.
- Elenbecestat 50mg total group showed less worsening of clinical assessment using Clinical Dementia Rating Sum of Boxes (CDR-SB) and Alzheimer’s Disease Composite Score (ADCOMS) at 18 months compared to placebo group. In study 202, elenbecestat suggested the acceptable tolerability.
- Elenbecestat has been selected by the Alzheimer’s Clinical Trials Consortium (ACTC) as treatments to be evaluated in upcoming clinical studies targeting primary prevention (A3 Study) and secondary prevention (A45 Study) of AD, and the screening will start in 2020.
2. Eisai Sponsored Symposium (Target Therapy for Preclinical Alzheimer’s Disease)
In this symposium, a presentation including issues and expectations for a biological definition, molecular pathways, and early treatment of AD were given by academic pioneers, and a lively discussion followed.
Cerebral Aβ accumulation, which is the causable substance of AD, begins one to two decades before the onset of memory symptoms in AD, therefore, the diagnosis and categorization based on pathology, not on the clinical symptoms, are required. In the latest AD classification ATN (Amyloid, Tau, Neurodegeneration / Neuronal Injury), the concept that AD is a disease that changes with a sequence of events in the Alzheimer’s continuum was explained. With the progress of biomarkers (blood, CSF, imaging), the current status, which enables determination of the stages of AD, including preclinical AD were introduced. According to the progress in these diagnosis technologies, it was indicated that therapeutic intervention in the preclinical AD is possible. Reducing production of toxic Aβ species through pathway-based targeted therapy is a rational approach in researching methods to arrest AD pathogenesis. In addition, the expectation for study design innovations, use of combination therapy, and establishment of the simplified blood-based diagnosis in the future were discussed.
Eisai aims to realize the prevention and cure of dementia through a multi-dimensional and holistic approach with a foundation of over 35 years of experience of drug discovery activities in the area of Alzheimer’s disease and dementia. Eisai strives to create innovative medicines as soon as possible to further contribute to addressing the unmet medical needs of, as well as increasing the benefits provided to, patients and their families.
* Elenbecestat, is being jointly developed by Eisai and Biogen Inc. (Headquarters: Cambridge, Massachusetts, United States, “Biogen”).
Public Relations Department,
Eisai Co., Ltd.
[Notes to editors]
1. About Elenbecestat (generic name, development code: E2609)
Discovered by Eisai, elenbecestat is an investigational next-generation oral candidate for the treatment of Alzheimer’s disease (AD) that inhibits BACE (beta amyloid cleaving enzyme). By inhibiting BACE, a key enzyme in the production of Aβ peptides, elenbecestat reduces Aβ production, and by reducing amyloid plaque formations in the brain, exerts disease modifying effects of potentially slowing the progression of AD. Currently, two global Phase III clinical studies (MISSION AD1/2) of elenbecestat in early AD including mild cognitive impairment (MCI) due to AD or the 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.
2. About joint development agreement between Eisai and Biogen for Alzheimer’s disease
Eisai and Biogen are collaborating on the joint development and commercialization of Alzheimer’s disease treatments. Eisai serves as the lead in the co-development of elenbecestat, a BACE inhibitor, and BAN2401, an anti-amyloid beta (Aβ) protofibril antibody, and the companies plan to pursue marketing authorizations for the two compounds worldwide. If approved, the companies will also co-promote the products in major markets, such as the United States, the European Union and Japan. As to BAN2401 and elenbecestat, both companies will equally split overall costs, including research and development expenses. Eisai will book all sales for elenbecestat and BAN2401 following marketing approval and launch, and profits will be equally shared between the companies.