Eisai's E2814 to Enter Phase 1 for Alzheimer Disease

December 7, 2018

The agent is designed to target the tau “seeds” that spread throughout the brain over the progression of the disease, with its first clinical assessment expected to occur in early 2019.

Teiji Kimura

Today Eisai announced that E2814, its first investigational therapeutic candidate from its drug discovery collaboration with University College London (UCL), is ready to enter phase 1 clinical trials in Alzheimer disease.1

The first clinical assessment of the agent is expected to occur in early 2019. E2814 is an anti-tau antibody which will be tested on its ability to slow Alzheimer progression in humans, operating on the tau pathology of the neurodegenerative disease. The agent is designed to target the tau “seeds” that spread throughout the brain over the progression of the disease in order to further build-up of neurofibrillary tangles and thus—possibly—slow the course of the disease.

"Significant unmet medical needs exist for neurodegenerative disorders such as Alzheimer's disease due to a lack of effective treatments that can prevent disease progression, and Eisai's mission is to contribute to overcoming these issues," said Teiji Kimura, the chief discovery officer of the Eisai Neurology Business Group. "By combining the knowledge of UCL, which conducts world-class research into neurodegenerative disorders and is the operational hub of the UK Dementia Research Institute, together with the knowledge of Eisai, who possesses a rich pipeline for dementia treatments, we are doing our utmost to link the results of joint research starting with E2814 to new medicines in order to contribute to patients who are awaiting curative therapies as soon as possible."

Eisai’s collaboration with UCL, agreed upon in 2012 to last for 6 years, has recently been extended until 2023, according to Eisai. The joint venture was brought together as part of the company’s Open Innovation strategy, a plan to collaborate with top researchers to attempt to translate investigative findings from the lab into treatments for those with neurodegenerative diseases. E2418 is one of those projects, established during the collaboration’s first phase.

Alan Thompson, MD, FRCP, the dean of UCL Faculty of Brain Sciences, said, "This unique research partnership brings together UCL's world-class academic research capabilities with the drug discovery expertise of industry. These results highlight the success of bringing together such complementary expertise."

Eisai currently has multiple therapies for Alzheimer disease in its pipeline, chief among them BAN2401, which has shown positive results thus far in slowing the progression of Alzheimer by acting as an antibody to amyloid-ß. That’s currently in phase 2 evaluation. Data announced in August 2018 showed that 18 months, the highest tested BAN2401 treatment dose of 10 mg/kg biweekly demonstrated a significant slowing of cognitive decline of 30% versus placebo (P = .034) as measured by the Alzheimer Disease Composite Score (ADCOMS), an Eisai-devised test drawing from 3 established Alzheimer assessment scales designed to detect subtle changes in those with early-stage disease and evaluate progression. It also reduced the formation of new beta-amyloid clusters in the brain and decreased existing clusters by 70% on average.2

Additionally, the company has aducanumab (in joint development with Biogen) and elenbecestat (in joint development with Purdue Pharma) for the early treatment of Alzheimer, both in phase 3. Eisai has also developed a phosphodiesterase-9 (PDE9) inhibitor, E2027, for the treatment of Dementia with Lewy Bodies, in phase 2/3.3

REFERENCES

1. First Drug Candidate From Eisai-UCL Research Collaboration To Enter Alzheimer's Disease Clinical Trials [press release]. Woodcliff Lake, NJ; Eisa Co; Published December 7, 2018. eisai.mediaroom.com/2018-12-07-First-Drug-Candidate-From-Eisai-UCL-Research-Collaboration-To-Enter-Alzheimers-Disease-Clinical-Trials. Accessed December 7, 2018.

2. Swanson C, Zhang Y, Dhadda S, et al. Treatment of Early AD Subjects With BAN2401, an Anti-Aβ Protofibril Monoclonal Antibody, Significantly Clears Amyloid Plaque and Significantly Reduces Clinical Decline. Paper presented

at:

2018 Alzheimer’s Association International Conference; July 25, 2018; Chicago, IL. July 25, 2018.

3.

Eisai to

Establish New Research Facility “Eisai Center for Genetics Guided Dementia Discovery” in Cambridge, Massachusetts in the United States [press release]. Tokyo, Japan: Eisai Co; Published June 13, 2018. eisai.com/news/2018/news201847.html. Accessed December 7, 2018.