A New Hope for Alzheimer’s Disease? Biogen and Eisai Move to Resubmit Aducanumab for FDA Approval

△NATIONAL INSTITUTE ON AGING,NIH

On October 22, 2019, Biogen and Eisai Co., Ltd. announced plans to seek FDA approval for the Alzheimer’s disease treatment drug aducanumab for the treatment of early-stage Alzheimer’s disease.

BiogenIt stated that analysis of a larger dataset showed that the Phase 3 EMERGE study of aducanumab met its primary endpoint. Specifically, compared with placebo, greater exposure to higher doses of aducanumab resulted in significant benefits in cognition and function (e.g., memory, orientation, and language) among patients in the treatment group. Patients in the treatment group also demonstrated improvements in activities of daily living, including personal finance management, household chores, and independent travel. If approved by the FDA, aducanumab would become the first therapy to reduce clinical decline in Alzheimer’s disease, as well as the first therapy to demonstrate that removal of amyloid beta (Aβ) can lead to better clinical outcomes.

The deposition of β-amyloid protein plaques in the brain is a major pathological feature of Alzheimer’s disease. A widely accepted hypothesis posits that an imbalance between the production and clearance of β-amyloid in the brain is a key early pathogenic factor in Alzheimer’s disease. Consequently, many scientists believe that clearing β-amyloid from the brain during the early stages is crucial for treating Alzheimer’s disease. However, numerous drugs developed based on this hypothesis have all failed in clinical trials. Last year, Pfizer announced that it would halt its drug research for Alzheimer’s and Parkinson’s diseases, laying off 300 related researchers. Eli Lilly and AstraZeneca also discontinued two Alzheimer’s-related trials last year; their collaboratively developed drug, lanabecestat, was deemed by an independent committee to have failed to meet efficacy targets. As early as 2017, Axovant Sciences, a company specializing in the development of therapeutics for Alzheimer’s and other dementias, acknowledged that experimental treatment with the drug intepirdine failed to improve patients’ memory, learning, and cognitive abilities.

△β-Amyloid Hypothesis [3]

Aducanumab is considered the last promising drug based on the β-amyloid hypothesis.

However, in March this year, based on the futility analysis results conducted by the Independent Data Monitoring Committee, Biogen and Eisai announced the termination of clinical trials for aducanumab, a drug for late-stage Alzheimer’s disease, causing their stock prices to drop by more than 29%. The failure of aducanumab has had far-reaching implications beyond Biogen itself. Aducanumab was considered the last remaining drug targeting β-amyloid protein; all previous drugs targeting this endpoint had failed without exception. The failure of aducanumab essentially signals the demise of the β-amyloid hypothesis.

Today, the torch of hope has been rekindled.

Following consultations with the FDA and analysis of extensive datasets, Biogen and Eisai plan to submit an application to the FDA in the next quarter for the use of aducanumab in the treatment of Alzheimer’s disease. If approved, this would be the first demonstration that clearing aggregated β-amyloid protein can reduce clinical decline.

Biogen is one of the world’s earliest global biotechnology companies, founded in 1978 by Charles Weissmann, Heinz Schaller, Kenneth Murray, and Nobel laureates Walter Gilbert and Phillip Sharp. Today, it specializes in the development of therapies for neurological diseases, autoimmune disorders, and cancer.

Eisai Co., Ltd. (Eisai) is a global leading R&D-based pharmaceutical company headquartered in Japan.

Aducanumab is a monoclonal antibody drug used for the treatment of early-stage Alzheimer's disease. Biogen obtained a license from Neurimmune, and in October 2017, Biogen and Eisai entered into a global collaboration to jointly develop aducanumab.

References

1\https://www.statnews.com/2019/10/22/biogen-to-submit-aducanumab/

2\http://investors.biogen.com/news-releases/news-release-details/biogen-plans-regulatory-filing-aducanumab-alzheimers-disease

3\Castellani R J, Plascencia-Villa G, Perry G. The amyloid cascadeand Alzheimer’s disease therapeutics: theory versus observation[J]. LaboratoryInvestigation, 2019: 1.

-End-