Eisai and Biogen Launch Phase 3 AHEAD 3-45 Trial of Lecanemab (BAN2401) in Preclinical Alzheimer’s Disease

Reposted from | Jike Pharma News

On July 13, the Alzheimer’s Clinical Trials Consortium (ACTC), Eisai, and Biogen announced the launch of a new Phase 3 clinical study (AHEAD 3-45) evaluating BAN2401 (an anti-amyloid-beta antibody) in individuals with preclinical (asymptomatic) Alzheimer’s disease (AD) who are cognitively normal but have moderate to high levels of amyloid-beta (Aβ) in the brain. The AHEAD 3-45 study will be conducted in the United States, Japan, Canada, Australia, Singapore, and Europe.

BAN2401 is a humanized anti-β-amyloid (Aβ) protofibril antibody. It selectively binds to soluble Aβ protofibrils, which are fibrillar complexes formed by the aggregation of Aβ proteins and represent an intermediate stage in the progression from soluble Aβ monomers to amyloid plaques. The development of BAN2401 has seen dramatic twists: at the 12-month mark of its Phase 2 clinical trial, BAN2401 did not demonstrate significant efficacy. However, data analysis at the 18-month timepoint indicated that BAN2401 not only reduced Aβ deposition in patients’ brains but also slowed cognitive decline. In March last year, Eisai initiated the Phase 3 clinical trial (Clarity AD), planning to enroll 1,566 patients with early-stage Alzheimer’s disease to receive BAN2401 at a dose of 10 mg/kg.

AHEAD 3-45 is a Phase 3 clinical study conducted collaboratively by the Alzheimer’s Clinical Trials Consortium (ACTC), funded by the National Institute on Aging (NIA) of the U.S. National Institutes of Health (NIH), and Eisai. In AHEAD 3-45, following a standard screening period, participants will be enrolled into one of two randomized, double-blind, placebo-controlled trials based on amyloid levels in the brain: the A45 trial and the A3 trial. A total of 1,400 subjects will be enrolled in the study and receive treatment with BAN2401 for 216 weeks.

The A45 trial will enroll cognitively unimpaired participants with elevated brain amyloid levels, aiming to prevent cognitive decline and inhibit the progression of Alzheimer’s disease (AD) pathology in the brain through administration of BAN2401. The primary endpoint of the A45 trial is the change from baseline in the Preclinical Alzheimer Cognitive Composite 5 (PACC5) after 216 weeks of treatment. Secondary endpoints include the change from baseline in brain amyloid levels measured by amyloid positron emission tomography (PET), as well as changes in brain tau levels measured by tau-PET and cognitive function indices.

The A3 trial will enroll cognitively unimpaired participants with moderate levels of amyloid in the brain and at risk for further Aβ accumulation. The primary endpoint of A3 is the change from baseline in brain amyloid levels as measured by amyloid PET. The secondary endpoint is the change from baseline in brain tau levels as measured by tau PET. Both trials include additional clinical assessment scales, imaging studies, blood biomarkers, and cerebrospinal fluid (CSF) as exploratory endpoints. Imaging and biofluids (particularly CSF) within the ATN (Amyloid, Tau, Neurodegeneration) biomarker framework, including Aβ1-42, Aβ1-40, t-Tau, p-Tau, neurogranin, and neurofilament light chain, will be used to evaluate the treatment effect on the progression of AD pathophysiological changes.

“We hope that initiating treatment earlier in the disease course may help prevent future cognitive decline. AHEAD 3-45 should provide critical answers regarding the optimal timing for anti-amyloid therapy,” said Dr. Reisa Sperling, Director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital and co-principal investigator of the ACTC. Dr. Aisen, Director of the Alzheimer’s Therapeutic Research Institute at the University of Southern California and head of the ACTC Coordinating Center, noted, “The mission of ACTC includes fostering public-private partnerships to conduct trials of promising candidate therapies. AHEAD 3-45 exemplifies the type of collaboration we need in the fight against Alzheimer’s disease.”

Dr. Lynn Kramer, Chief Clinical Officer and Chief Medical Officer of Eisai’s Neurology Business Group, said, “Launching the AHEAD 3-45 clinical trial of BAN2401 for early-stage Alzheimer’s disease (AD) in collaboration with ACTC is an exciting milestone for us. This represents the next step in developing precision therapies for AD using biomarker panels, as part of our human health care mission; we are committed to bringing transformational change to patients worldwide, their families, and healthcare professionals.”

Note: This article aims to introduce advances in medical and health research and does not constitute a recommendation for treatment plans. For guidance on treatment options, please consult a qualified healthcare provider at a reputable hospital.

References:

[1] Initiation Of New Phase III Clinical Study (AHEAD 3-45) Of BAN2401 Preclinical (Asymptomatic) Alzheimer's Disease. Retrieved 2020-07-14, from https://www.prnewswire.com/news-releases/initiation-of-new-phase-iii-clinical-study-ahead-3-45-of-ban2401-preclinical-asymptomatic-alzheimers-disease-301092593.html

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