First Patient Dosed in Phase 2 Extension Study of Sabirnetug in Early Alzheimer Disease

Acumen Pharmaceuticals, announced that the first participant has been dosed in an open-label extension (OLE) phase 2 clinical trial titled ALTITUDE-AD (NCT06335173) aimed at evaluating sabirnetug (ACU193) in people with early Alzheimer disease (AD).¹ 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 month for an additional 52 weeks.

“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,” Eric Siemers, MD, chief medical officer of Acumen Pharmaceuticals, said in a statement. "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."¹

Sabirnetug is a humanized monoclonal antibody (mAb) discovered and developed based on its selectivity for soluble amyloid beta oligomers (AβOs). By selectively targeting toxic soluble AβOs, sabirnetug aims to address the hypothesis that soluble AβOs are an early and persistent underlying cause of the neurodegenerative process in AD. Sabirnetug has been granted a fast-track designation by the FDA and could become the first approved treatment to selectively target toxic AβOs.²

The initial ALTITUDE-AD study began in 2024 as a multi-center, randomized, double-blind, placebo-controlled phase 2 study designed to evaluate the efficacy and safety of sabirnetug infusions administered once every 4 weeks. In total, 542 individuals with early AD (mild cognitive impairment or mild dementia due to AD) were enrolled at multiple investigative sites located in the United States, Canada, the European Union, and the United Kingdom.³ 

READ MORE: Acumen Pharmaceuticals’ Phase 2 Advancements in Alzheimer Disease Screening: Todd Feaster, PsyD 

Patients eligible for ALTITUDE-AD weighed between 66 and 323 lb who consented to APOE4 genotyping. Additionally, participants met NIA-AA criteria for MCI because of AD or probable AD, with MMSE scores of 22–30, a CDR-GS of 0.5–1.0, a CDR Memory Box score at least 0.5, and biomarker-confirmed cerebral amyloid by PET or CSF. Furthermore, participants remained on stable cholinesterase inhibitors or memantine, had reliable study partner, and followed appropriate reproductive precautions. 

Key exclusions included MRI contraindications or imaging findings incompatible with MCI/AD—such as ARIA-E, >4 ARIA-H, or superficial siderosis. Significant or unstable neurological disorders (e.g., stroke, other dementias, uncontrolled seizures), major medical illnesses that may impair cognition or safety, recent malignancy, and psychiatric conditions likely to confound cognitive outcomes, including a GDS-SF score of more than 10 or current major depressive disorder were also basis for exclusion.

Earlier this year, Acumen presented an additional poster at the 2025 Alzheimer’s Association International Conference (AAIC), held July 27 to 30 in Toronto, Canada, that demonstrated implementing a blood-based pTau217 screening assay reduced clinical trial screening costs by approximately 40%. The phase 2 ALTITUDE-AD study was used as the input example and Acumen noted that this 2-part screening process using plasma pTau217 not only cut costs but also improved trial efficiency by reducing unnecessary amyloid PET scans and lumbar punctures.² 

Among participants screened to date, 48% had pTau217 plasma concentrations of at least 0.15 pg/mL, of which 78% met study amyloid burden eligibility requirements after confirmatory testing of amyloid pathology. Of participants who underwent amyloid PET imaging or CSF testing, 79% and 62% met the amyloid burden inclusion criterion, respectively.

The previously completed phase 1 study, titled INTERCEPT-AD (NCT06335173), aimed to assess the safety, pharmacokinetics, and exploratory measures including target engagement, biomarker effects, and clinical efficacy of sabirnetug in participants with early symptomatic AD. Findings from the study indicated favorable safety, tolerability, dosing, and target engagement data that supported the design of the ongoing phase 2 ALTITUDE-AD study.⁴

Additional results from INTERCEPT-AD show that a larger percentage of participants receiving sabirnetug (56.3%) versus placebo (42.9%) had at least one treatment-emergent adverse event. Furthermore, approximately 29% in each group considered related to study drug. Most events were mild-to-moderate in severity.

REFERENCES
1. Acumen Pharmaceuticals Announces First Participant Dosed in Phase 2 Open-Label Extension Study of Sabirnetug in People with Early Alzheimer’s Disease. Acumen Pharmaceuticals. News Release. November 17, 2025. Accessed November 18, 2025. 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
2. Acumen Pharmaceuticals presents studies showing the utility of a pTau217 assay in screening for a phase 2 Alzheimer’s disease trial and validates sabirnetug oligomer-selectivity, at the Alzheimer’s Association International Conference (AAIC) 2025. News release. Acumen Pharmaceuticals. July 28, 2025. Accessed August 12, 2025. https://investors.acumenpharm.com/news-releases/news-release-details/acumen-pharmaceuticals-presents-studies-showing-utility-ptau217
3. A Study to Evaluate Efficacy and Safety of Intravenous Sabirnetug in Participants With Early Alzheimer's Disease (ALTITUDE-AD) (ALTITUDE-AD). Clinicaltrials.gov. Accessed November 19, 2025. Updated 
4. 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