Alzheimer Agent Sabirnetug Misses Primary Endpoint, Acumen Halts Development

Acumen Pharmaceuticals announced that sabirnetug (ACU193), an investigational antibody targeting toxic amyloid beta oligomers, did not meet the primary endpoint of the phase 2 ALTITUDE-AD trial in early Alzheimer disease. The company said it will cease clinical development of sabirnetug and evaluate its strategic options.¹

Daniel O'Connell, chief executive officer of Acumen, said the company was “disappointed the trial did not meet its primary endpoint” and expressed “compassion and hope for future therapeutic options for patients with Alzheimer's disease and their families.” Acumen plans to also halt the trial's open-label extension, and said it will take steps to conserve cash while exploring strategic options, including its Enhanced Brain Delivery (EBD) platform.

ALTITUDE-AD (NCT06335173) was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled 542 participants with early Alzheimer disease, defined as mild cognitive impairment or mild dementia due to Alzheimer disease, at sites in the US, Canada, the European Union, and the UK. Participants received sabirnetug infusions at 35 mg/kg or 50 mg/kg, or placebo, once every 4 weeks. The primary endpoint was change from baseline in cognitive and functional decline, measured by the Integrated Alzheimer's Disease Rating Scale (iADRS), at 18 months.

READ MORE: Examining Trontinemab in Early Alzheimer Disease: The Phase 3 TRONTIER 1 and 2 Trials

Acumen reported no meaningful difference between either sabirnetug dose and placebo on the primary endpoint, and said key secondary endpoints, including the Clinical Dementia Rating Sum of Boxes (CDR-SB), did not reach statistical significance. An analysis of amyloid PET imaging did show a statistically significant, dose-dependent reduction in amyloid plaque load at weeks 36 and 76, though the company said it does not expect additional fluid biomarker and imaging data, expected in the coming weeks, to change the trial's efficacy conclusions.¹

Sabirnetug was generally well tolerated, with amyloid-related imaging abnormalities with edema (ARIA-E) observed in approximately 10% of sabirnetug-treated participants; the release did not report ARIA-E rates by dose, ARIA with hemosiderin deposition (ARIA-H) rates, or other adverse event data.

From Fast Track designation to a failed phase 2 trial

The FDA granted sabirnetug Fast Track designation for early Alzheimer disease in October 2022, when Acumen described it as the first clinical-stage therapy to selectively target toxic soluble amyloid beta oligomers rather than amyloid plaques directly, an approach the company said could carry a lower risk of ARIA than plaque-targeting antibodies.²

In the phase 1 INTERCEPT-AD trial, a single- and multiple-ascending-dose study, exploratory analyses found dose-dependent reductions in amyloid plaque load on PET imaging and identified amyloid-related imaging abnormalities, including a higher rate of ARIA-E among APOE ε4 carriers, findings the company said supported the dose selection and design of the subsequent ALTITUDE-AD trial.³

Acumen dosed the first participant in a planned open-label extension of ALTITUDE-AD in November 2025, intended to generate longer-term safety and efficacy data; the company said that extension will now be discontinued along with the rest of the sabirnetug program.⁴

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. News release. Acumen Pharmaceuticals. Published October 30, 2026. Accessed November 2, 2026. https://investors.acumenpharm.com/news-releases/news-release-details/acumen-pharmaceuticals-announces-topline-results-phase-2
2. Acumen's ACU193, an anti-amyloid beta oligomer antibody, granted FDA Fast Track designation for Alzheimer's disease. News release. Acumen Pharmaceuticals. Published October 24, 2022. Accessed November 2, 2026. https://www.globenewswire.com/news-release/2022/10/24/2539885/0/en/Acumen-s-ACU193-an-Anti-Amyloid-Beta-Oligomer-Antibody-Granted-FDA-Fast-Track-Designation-for-Alzheimer-s-Disease.html
3. 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. doi:10.1016/j.tjpad.2024.100005
4. Acumen Pharmaceuticals announces first participant dosed in phase 2 open-label extension study of sabirnetug in people with early Alzheimer's disease. News release. Acumen Pharmaceuticals. Published November 17, 2025. Accessed November 2, 2026. https://www.globenewswire.com/news-release/2025/11/17/3189097/0/en/Acumen-Pharmaceuticals-Announces-First-Participant-Dosed-in-Phase-2-Open-Label-Extension-Study-of-Sabirnetug-in-People-with-Early-Alzheimer-s-Disease.html