Acumen Pharma Showcases pTau217 Screening in Phase 2 Sabirnetug Trial for Early Alzheimer's at CTAD Conference

Acumen Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company focused on developing treatments for Alzheimer’s disease (AD), has presented new data regarding the pTau217 assay. This assay is being used to screen potential participants for the ongoing Phase 2 ALTITUDE-AD clinical trial of sabirnetug. The updated results were shared at the 17th Annual Clinical Trials on Alzheimer's Disease (CTAD) conference.

The study highlights the effectiveness of the pTau217 assay in identifying suitable participants for the trial, which aims to reduce the need for more invasive and burdensome procedures like amyloid PET scans and lumbar punctures. Compared to the Phase 1 INTERCEPT-AD trial, which did not utilize the pTau217 assay, the Phase 2 ALTITUDE-AD trial has seen a higher proportion of participants meeting the amyloid PET or CSF-based inclusion criteria. This improvement in participant selection efficiency has minimized the number of unnecessary procedures for individuals not qualifying for the study.

“The pTau217 screening assay is a crucial part of clinical trials for Alzheimer's treatments. It helps avoid invasive lumbar punctures and unnecessary radiation exposure from amyloid PET scans,” stated Todd Feaster, Senior Clinical Research Scientist at Acumen Pharmaceuticals. “We are pleased that our screening strategy is effective and simplifying the trial enrollment process. These assays can lessen the burden on patients, clinical trial investigators, and their teams, fostering a more compassionate trial experience.”

ALTITUDE-AD is a Phase 2, multi-center, randomized, double-blind, placebo-controlled study designed to assess the efficacy and safety of sabirnetug. The trial will include approximately 540 adults aged 50 to 90 years and is currently enrolling participants at 75 sites in the U.S., Canada, EU, and U.K. Acumen anticipates completing enrollment by the first half of 2025.

A key eligibility requirement for ALTITUDE-AD and other amyloid-targeting therapy trials is confirming cerebral amyloid build-up via PET scan or CSF, which can be time-consuming and challenging. However, the pTau217 assay, which measures plasma concentrations of the biomarker pTau217, offers a strong indicator of AD pathology. Used at U.S. trial sites as an initial enrichment approach, the assay helps identify potential participants with a high likelihood of amyloid presence in the brain, confirmed later by PET scan or CSF.

The pTau217 assay has proven to be an effective tool for identifying participants likely to qualify for the ALTITUDE-AD study. Establishing a pTau217 threshold of ≥0.15 pg/mL for enrichment purposes, the study has excluded over half of potential participants with plasma p-tau217 levels below 0.15 pg/mL. Among those with p-tau217 levels at or above 0.15 pg/mL, 74% met the amyloid burden eligibility criteria following confirmatory assessments, compared to 40% in the Phase 1 INTERCEPT-AD trial.

“The study demonstrates our dedication to advancing next-generation Alzheimer's treatments and pioneering clinical trial designs for an improved patient experience,” commented Daniel O’Connell, President and CEO of Acumen. “We are delighted with the enrollment pace in ALTITUDE-AD, reflecting the strong interest in our approach and the desire to bring innovative solutions to those affected by Alzheimer’s.”

Sabirnetug (ACU193) is a humanized monoclonal antibody developed to selectively target soluble amyloid beta oligomers (AβOs), which are highly toxic and pathogenic compared to Aβ monomers and amyloid plaques. These AβOs are believed to be potent neurotoxins that impair synaptic function and cause neurodegeneration. Sabirnetug aims to address the hypothesis that soluble AβOs are an early and persistent cause of the neurodegenerative process in AD. The drug has received Fast Track designation for early AD treatment from the U.S. Food and Drug Administration and is currently being evaluated in the Phase 2 ALTITUDE-AD study.

Initiated in 2024, the ALTITUDE-AD trial will assess the efficacy and safety of sabirnetug infusions administered every four weeks in slowing cognitive and functional decline compared to placebo in participants with early AD. The global study is currently ongoing at various sites in the United States, Canada, the United Kingdom, and the European Union.