ACTC, Eisai & Biogen announce initiation of new phase III clinical study of BAN2401 for preclinical Alzheimer’s disease

The Alzheimer’s Clinical Trials Consortium , Eisai Co., Ltd and Biogen Inc announced that a new phase III clinical study (AHEAD 3-45) of BAN2401, an anti-amyloid beta (Aß) protofibril antibody, has been initiated in the United States of America for individuals with preclinical Alzheimer’s disease (AD), meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains.

Currently, BAN2401 is being studied in a pivotal phase III clinical study in symptomatic early AD (Clarity AD), following the outcome of the phase II clinical study (Study 201). The AHEAD 3-45 will be conducted in the US, Japan, Canada, Australia, Singapore, and Europe.

AHEAD 3-45 is a phase III clinical study, conducted as a public-private partnership between the ACTC, funded by the National Institute on Aging, part of the National Institutes of Health, and Eisai. After a common screening period in AHEAD 3-45, participants will be enrolled into one of two randomized, double-blind, placebo controlled trials based on the level of amyloid in the brain: the A45 trial and the A3 trial.

A total of 1,400 participants will be enrolled in the study and treated with BAN2401 for 216 weeks. The A45 trial will enroll cognitively unimpaired participants who have elevated levels of amyloid in the brain, and aims to prevent cognitive decline and suppress the progression of brain AD pathology with BAN2401 administration. The primary endpoint for A45 is the change from baseline in the Preclinical Alzheimer Cognitive Composite 5 (PACC5) at 216 weeks of treatment. Secondary endpoints are changes from baseline in brain amyloid levels as measured by amyloid positron emission tomography (PET) and in brain tau levels as measured by tau PET and Cognitive Function Index, a participant and study partner reported outcome.

The A3 trial will enroll cognitively unimpaired participants who have an intermediate amount of amyloid in the brain, and who are at high risk for further Aß accumulation. The primary endpoint for A3 is change from baseline in brain amyloid levels as measured by amyloid PET.

The secondary endpoint is change from baseline in brain tau levels as measured by tau PET. Both trials include additional clinical assessment scales, imaging, blood biomarkers and cerebrospinal fluid (CSF) in a subset, as exploratory endpoints. An ATN (Amyloid, Tau, Neurodegeneration) biomarker panel of imaging and biofluid, especially CSF, markers including Aß 1-42, Aß 1-40, t-tau, p-tau, neurogranin, neurofilament light chain, will be used to evaluate therapeutic effects on the progression of AD pathophysiologic changes.

“It is hoped that initiating treatment much earlier in the disease process may be advantageous in preventing future cognitive decline. The AHEAD 3-45 should provide critically important answers about the optimal time to intervene with anti-amyloid therapy” said Dr.ReisaSperling, director, Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital and co-Principal Investigator, ACTC.

Dr.Aisen, director of the University of Southern California Alzheimer’s Therapeutic Research Institute, which serves as the coordinating center for the ACTC, noted, “The mission of the ACTC includes the development of public-private partnerships to conduct trials of promising candidate therapies. AHEAD 3-45 is the type of collaboration we need in the fight against Alzheimer’s disease.”

“The initiation of AHEAD 3-45 with BAN2401, focused on therapies for the earliest stages of the AD continuum through our collaboration with the ACTC group, marks an exciting time for us,” says Lynn Kramer, M.D., chief clinical officer, Neurology Business Group, Eisai. “This represents a next step in developing precision therapies for AD using biomarker panels as part of our human health care mission; we are committed to making a difference for patients, their families, and health care professionals across the globe.”

BAN2401 is a humanized, monoclonal, anti- Aß soluble aggregate (protofibril) antibody obtained through collaboration research between Eisai and BioArctic AB (Sweden). BAN2401 selectively binds to neutralize and eliminate toxic Aß protofibrils that are thought to be a causative factor for AD. This suggests that BAN2401 may have the potential to have an effect on disease pathology and to slow the progression of AD.

Study 201 demonstrated a statistically significant slowing of disease progression and decreasing of brain Aß accumulation as the first late-stage large scale clinical study for early AD, and successfully showed potential disease-modifying effects. It is being conducted along with the 201 Open-Label Extension (OLE) study (Open-label continuous administration study) and one pivotal clinical study (Clarity AD). Eisai and Biogen Inc. have entered into a collaboration to develop and commercialize BAN2401.