Biogen and Eisai, in collaboration with BioArctic and the Alzheimer’s Clinical Trials Consortium (ACTC), have announced the initiation of a phase 3 study of their experimental Alzheimer’s treatment BAN2401.
The study will evaluate the therapeutic effect of BAN2401 on the progression of Alzheimer’s disease (AD) in individuals in preclinical, asymptomatic stages of the disease. BAN2401 is an anti-amyloid beta (Aβ) protofibril antibody, designed to selectively bind to neutralise and eliminate toxic Aβ protofibrils that are thought to be one of the factors causing AD.
The AHEAD 3-45 programme includes two trials, A3 and A45, which aim to evaluated to potential of BAN2401 to reduce the accumulation of harmful amyloid beta aggregates in the brain, and also prevent cognitive decline resulting from AD.
The two trials will involve participants with different levels of amyloid beta in the brain. The A3 trial will enrol participants who have an intermediate amount of amyloid beta in the brain and who are at high-risk for further amyloid beta accumulation. The A45 trial will enrol participants with elevated levels of amyloid beta in the brain.
“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 Reisa Sperling, director, Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital and co-principal investigator, ACTC.
Biogen and Eisai are also currently studying BAN2401 in a pivotal phase 3 clinical study in symptomatic early AD, after promising results in a phase 2 trial. In this mid-stage trial, high-dose BAN2401 achieved a statistically significant slowdown in the progression of cognitive decline, measured using the ADCOMS symptom scale, as well as reduction in amyloid deposits in the brain at the 18-month time-point.
However, there was a concern that patients on lower doses of the amyloid-targeting drug seemed to decline more quickly than those on placebo. Although the partner companies suggested that this could be a result of an imbalance between the groups at enrolment in patients with a genetic predisposition for rapid progression, the lack of a clear dose response on clinical endpoints cast doubt on the efficacy of the drug.
Despite this, the fact that BAN2401 showed any impact on disease progression is noteworthy, given the string of amyloid-targeting drugs that have previously failed in clinical trials. For Alzheimer’s patients and their loved ones, the potential of this treatment signals the revival of hope in a disease area that has not seen a new therapy approved for years.
Adding to that hope is Biogen’s other investigational AD drug, aduaducanumab, after the company announced it had completed a regulatory submission to the US Food and Drug Administration (FDA) last week.