DIAN-TU SELECTS LECANEMAB AS BACKGROUND ANTI-AMYLOID THERAPY IN CLINICAL TRIAL EVALUATING INVESTIGATIONAL THERAPY TARGETING TAU FOR DOMINANTLY INHERITED ALZHEIMER’S DISEASE
Eisai’s anti-microtubule binding region (MTBR) tau antibody E2814 previously selected as the first investigational therapy among anti-tau drugs for the DIAN-TU Tau Next Generation trial
Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, has an agreement with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to amend the clinical study (Tau NexGen) design to include a background anti-amyloid agent. The Tau NexGen clinical study was originally designed to focus on therapies that target tau. With increasing evidence from clinical studies showing that targeting amyloid can reduce biomarkers of Alzheimer’s disease (AD), the Tau NexGen clinical trial leaders selected Eisai’s investigational anti-amyloid beta (Aβ) protofibril antibody lecanemab as the background anti-amyloid agent.
The purpose of the Tau NexGen study is to assess the safety, tolerability, biomarker and cognitive efficacy of investigational therapies in people who have an Alzheimer’s disease-causing gene mutation. The study will evaluate if treatment with study drug slows the rate of progression of cognitive impairment and improves disease-related biomarkers.
People who have this genetic mutation of dominantly inherited Alzheimer’s disease (DIAD) are known to develop AD and will likely develop symptoms at around the same age their affected parents did, often in their 50s, 40s or even 30s. In March 2021, the DIAN-TU selected anti-microtubule binding region (MTBR) tau antibody E2814, which was created from collaboration research between Eisai and University College London, as the first investigational medicine among anti-tau drugs for the DIAN-TU tau study.
In the amended Tau NexGen study, symptomatic participants will be administered lecanemab for six months before being randomly assigned to also receive the anti-tau drug or a placebo. Since amyloid plaques accumulate before tau tangles in AD, this study design allows the researchers to assess whether amyloid removal clears the way for the anti-tau drug to function most effectively. Pre-symptomatic participants will be randomly assigned to receive the anti-tau drug or a placebo for a year before beginning lecanemab administration. By staggering the drugs in this way, the researchers will be able to evaluate the effects of the anti-tau drug alone before assessing the effects of the two drugs together. The primary endpoint is a slowing of tau accumulation in the brain in symptomatic participants, as seen on PET brain scans. As a secondary endpoint, the researchers will evaluate whether the investigational therapies affect levels of a specific kind of tau — phosphorylated tau 217 — in the cerebrospinal fluid of pre-symptomatic participants. If these primary and secondary endpoints are positive in the analysis two years after the start of study, the study will be extended for another two years to assess whether the drug slows cognitive decline and has further effects on tau pathology.
“With growing evidence that removing amyloid plaques has biologically beneficial effects on amyloid and tau, we believe that targeting both Alzheimer’s disease pathologies — amyloid plaques and tau tangles — at the same time can provide the highest chance of success,” said principal investigator Randall J. Bateman, M.D., director of DIAN-TU and the Charles F. and Joanne Knight Distinguished Professor of Neurology at Washington University.
“Eisai’s anti-MTBR tau antibody E2814 was chosen as the first investigational therapy among anti-tau drugs for the groundbreaking Dominantly Inherited Alzheimer Network Trials Unit Tau NexGen, which was originally designed to target tau proteins. The growing body of evidence suggesting the removal of amyloid plaque slows cognitive decline is creating new possibilities to potentially fight this devastating disease. Eisai is proud that our investigational anti-amyloid beta protofibril antibody lecanemab has been selected as the background anti-amyloid agent in this arm of the study,” said Lynn Kramer, M.D., FAAN, Chief Clinical Officer, Neurology Business Group, Eisai Co., Ltd. “In our Phase 2b study, lecanemab 10 mg/kg biweekly dosing without titration, demonstrated robust clearance of the brain amyloid plaques from early stage of administration and slowed cognitive decline in people living with early AD. Encouragingly, the rate of amyloid-related imaging abnormalities-edema/effusion for this same dosing was 9.9% with less than 2% being symptomatic.”
Eisai positions neurology as a key therapeutic area, and it will continue to create innovation in the development of novel medicines based on cutting-edge neurology research as it seeks to contribute further to improving the benefits of affected individuals and their families in diseases with high unmet needs, such as dementia including AD. Our vision is clear: a world free of neurodegeneration.