Anti-Amyloid-ß Oligomer Antibody ACU193 Gains FDA Fast Track Designation


ACU193, an antibody developed based on its selectivity for soluble amyloid-ß oligomers, is currently being assessed in a phase 1 trial, with a potential phase 2/3 trial in the near future.

Daniel O’Connell, president and chief executive officer, Acumen

Daniel O’Connell

According to a recent announcement, the FDA granted fast track designation to Acumen’s investigational humanized monoclonal antibody ACU193 for the treatment of patients with early Alzheimer disease (AD).1

ACU193, the first clinical-stage therapeutic that selectively targets toxic soluble amyloid-ß oligomers (AßOs) originally emerged from a research and development collaboration forged in 2004 between Acumen and Merck. Acumen later regained development rights in 2011, and following that, preclinical studies of the therapeutic began to arise. Years later, in 2021, the company initiated INTERCEPT-AD, the first-in-human, phase 1 trial of ACU-193 in patients with early AD. Acumen is also currently planning a phase 2/3 trial of the agent.

"We are encouraged to receive Fast Track designation for ACU193, reflecting its potential clinical utility to treat Alzheimer’s disease, Daniel O’Connell, president and chief executive officer, Acumen, said in a statement.1 "We look forward to collaborating with the FDA to advance the development of ACU193. Treating Alzheimer’s disease ultimately requires therapies that target different components of the disease pathway, and we are developing ACU193 with the goal of providing patients with more treatment options."

INTERCEPT-AD is an ongoing single-ascending dose and multiple ascending dose, placebo-controlled study expected to include 62 patients with mild cognitive impairment (MCI) or mild dementia due to AD. Expected to complete in December 2022, the trial’s primary outcome measures include incidence and severity of treatment related adverse events (TEAEs) or serious TEAEs, changes in 12-lead ECGs, the Columbia-Suicide Severity Rating Scale, and in clinical laboratory tests and MRI findings.

Previous research has shown that some types of toxic soluble AßOs have been found to interact within synapses which leads to altered neuronal function, and can initiate and perpetuate the process of neurodegeneration, ultimately leading to cell death. The mouse version of ACU193, ACU-3B3, reportedly showed an ability to block amyloid-ß oligomer-induced calcium elevation in hippocampal neurons in culture, and reduced amyloid pathology and behavioral deficits in AD models.2

Because of its unique binding profile, ACU193 has potential to provide therapeutic benefit with low risk of amyloid-related imaging abnormalities, traditionally a major concern for amyloid-related therapies. This is in part because the agent blocks the toxic effects of AßOs without directly targeting amyloid-plaques, which is quite contrary to the direction of several others therapeutics in development. With the new designation, Acumen will have more frequent engagement with the FDA to discuss development plans for the study design of ACU193, as well as ensure collection of appropriate data to support evaluation for potential approval.1

1. Acumen ACU193, an anti-amyloid beta oligomer antibody, granted FDA fast track designation for Alzheimer disease. News release. October 24, 2022. Accessed November 17, 2022.
2. Wang X, Kastanenka KV, Arbel-Ornath M, et al. An acute functional screen identifies an effective antibody targeting amyloid-ß oligomers based on calcium imaging. Scientific Reports. 2018;8:4634. doi:10.1038/s41598-018-22979-2
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