Sabirnetug Misses Primary Endpoint in Phase 2 Alzheimer Disease Trial

The ALTITUDE-AD phase 2 trial of sabirnetug (ACU193) did not meet its primary endpoint in participants with early Alzheimer disease.¹ Developers, Acumen Pharmaceuticals, plan to cease development of the investigational monoclonal antibody, including the open-label extension portion of the trial.¹

ALTITUDE-AD, initiated in 2024, is a multicenter, randomized, double-blind, placebo-controlled trial of sabirnetug infusions administered once every 4 weeks.¹ The study enrolled 542 individuals with early Alzheimer disease (defined as mild cognitive impairment or mild dementia due to Alzheimer disease) at sites in the United States, Canada, the European Union, and the United Kingdom. Participants were evaluated at 2 dose levels, 35 mg/kg and 50 mg/kg, compared with placebo.

According to Acumen, the trial did not meet its primary endpoint of change from baseline in cognitive and functional decline, measured by the Integrated Alzheimer’s Disease Rating Scale (iADRS) at 18 months, at either dose.¹ The company also reported that key secondary endpoints, including the Clinical Dementia Rating–Sum of Boxes (CDR-SB), did not reach statistical significance and showed no meaningful difference between either sabirnetug arm and placebo.¹ Current information did not report P values or effect sizes for these endpoints.

Amyloid plaque load, measured by positron emission tomography standardized uptake value ratio (SUVr), showed statistically significant reductions for both dose levels at weeks 36 and 76.¹ Acumen described sabirnetug as generally well tolerated, with amyloid-related imaging abnormalities with edema (ARIA-E) observed in approximately 10% of sabirnetug-treated participants.¹

“While we are disappointed the trial did not meet its primary endpoint, we express our compassion and hope for future therapeutic options for patients with Alzheimer’s disease and their families,” said Daniel O’Connell, MBA, chief executive officer of Acumen.¹

Sabirnetug is a humanized monoclonal antibody designed to selectively target toxic soluble amyloid beta oligomers (AβOs), which the company describes as a highly toxic and pathogenic form of amyloid beta relative to monomers and plaques. The antibody was developed to test the hypothesis that soluble AβOs are an early and persistent underlying cause of neurodegeneration in Alzheimer disease. The FDA had granted sabirnetug Fast Track designation for the treatment of early Alzheimer disease, and ALTITUDE-AD followed what the company described as positive results in its phase 1 INTERCEPT-AD trial.

Acumen expects to receive and analyze additional data from ALTITUDE-AD in the coming weeks, including fluid biomarker and additional imaging data, but does not expect these data to change the efficacy conclusions of the trial.¹

References

1. Acumen Pharmaceuticals announces topline results from phase 2 ALTITUDE-AD clinical trial of sabirnetug (ACU193) for the treatment of early Alzheimer’s disease; trial did not meet primary endpoint. Press release. October 30, 2026. Accessed October 30, 2026. https://investors.acumenpharm.com/news-releases/news-release-details/acumen-pharmaceuticals-announces-topline-results-phase-2

2. Siemers E, Feaster T, Sethuraman G, et al. INTERCEPT-AD, a phase 1 study of intravenous sabirnetug in participants with mild cognitive impairment or mild dementia due to Alzheimer’s disease. J Prev Alzheimers Dis. 2025;12(1):100005.