Acumen Pharmaceuticals has announced the dosing of the first participant in the open-label extension (OLE) portion of its Phase 2 ALTITUDE-AD clinical trial evaluating sabirnetug (ACU193) in people with early Alzheimer's disease. The milestone represents a significant step forward in the company's development of a novel therapeutic approach targeting toxic soluble amyloid beta oligomers.
Extension Study Design and Objectives
The open-label extension provides all participants who completed the 18-month placebo-controlled portion of ALTITUDE-AD with the opportunity to receive sabirnetug at 35 mg/kg administered intravenously once every four weeks for an additional 52 weeks. Clinical measures and safety monitoring will remain consistent with the placebo-controlled portion of the study.
"Initiating the open-label extension study represents our ongoing commitment to the participants who have contributed in ALTITUDE-AD and provides us with valuable long-term safety and efficacy data," said Eric Siemers, M.D., Chief Medical Officer of Acumen Pharmaceuticals. "We expect the results of this study to supplement the broader data package supporting sabirnetug, and we look forward to gathering additional insights that will support our continued development of this potentially differentiated therapeutic approach."
Novel Mechanism of Action
Sabirnetug represents a differentiated approach to Alzheimer's treatment as the first humanized monoclonal antibody to demonstrate selective target engagement of amyloid beta oligomers (AβOs) in AD patients. These soluble and highly synaptotoxic forms of amyloid-beta accumulate early in Alzheimer's disease and serve as persistent triggers of synaptic dysfunction and neurodegeneration.
The drug was discovered and developed based on its selectivity for soluble amyloid beta oligomers relative to Aβ monomers and amyloid plaques. Soluble AβOs have been observed to be potent neurotoxins that bind to neurons, inhibit synaptic function and induce neurodegeneration. By selectively targeting these toxic soluble AβOs, sabirnetug aims to address the hypothesis that they are an early and persistent underlying cause of the neurodegenerative process in Alzheimer's disease.
Phase 1 Results and Regulatory Status
In the Phase 1 INTERCEPT-AD trial, sabirnetug demonstrated a favorable safety profile with low overall rates of ARIA-E, evidence of target engagement, and positive effects on fluid and imaging biomarkers including reduction in amyloid plaques in the two groups of participants given the highest doses.
The drug has been granted Fast Track designation for the treatment of early AD by the U.S. Food and Drug Administration, reflecting the regulatory agency's recognition of the potential therapeutic benefit and unmet medical need in this patient population.
ALTITUDE-AD Trial Overview
Initiated in 2024, ALTITUDE-AD is a Phase 2, multi-center, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of sabirnetug infusions administered once every four weeks in slowing cognitive and functional decline compared to placebo in participants with early Alzheimer's disease.
The study has enrolled 542 individuals with early Alzheimer's disease, including those with mild cognitive impairment or mild dementia due to AD, at multiple investigative sites located in the United States, Canada, the European Union and the United Kingdom. Acumen expects to report topline results from ALTITUDE-AD in late 2026.
Company Development Pipeline
Beyond the current Phase 2 trial, Acumen is investigating a subcutaneous formulation of sabirnetug using Halozyme's proprietary ENHANZE® drug delivery technology. The company is also collaborating with JCR Pharmaceuticals to develop an Enhanced Brain Delivery (EBD™) therapy for Alzheimer's disease utilizing a transferrin-receptor-targeting blood-brain barrier-penetrating technology.
Acumen's scientific founders pioneered research on AβOs, which a growing body of evidence indicates are early and persistent triggers of Alzheimer's disease pathology. The company is headquartered in Newton, Massachusetts, and continues to focus on advancing this novel therapeutic approach for treating one of the most challenging neurodegenerative diseases.
