Acumen Pharmaceuticals has presented updated data on a validated research-use plasma pTau217 assay to screen potential participants in the ongoing Phase 2 ALTITUDE-AD clinical trial of sabirnetug, at the 17th Annual Clinical Trials on Alzheimer’s Disease (CTAD) conference.

The study found that this enrichment screening approach is resulting in a higher proportion of participants who meet the amyloid PET or CSF-based inclusion criteria compared to Acumen’s Phase 1 INTERCEPT-AD trial, which did not use this approach.

Furthermore, the enrichment approach is resulting in a more efficient participant selection process that reduces unnecessary amyloid PET scans or lumbar puncture (LP) procedures among people who are not eligible to continue in screening.

“The pTau217 screening assay enrichment approach is an important part of the clinical trial process for Alzheimer’s treatments because it could spare patients from invasive lumbar punctures and unnecessary radiation exposure with an amyloid PET scan,” said Todd Feaster, Psy.D., Senior Clinical Research Scientist at Acumen Pharmaceuticals and the study presenter.

“We are encouraged to see that our screening strategy is performing as intended and streamlining the trial enrollment process overall. Screening assays like this can reduce burden for patients, clinical trial investigators and their staff and foster a more compassionate and sustainable clinical trial experience.” Feaster added.

ALTITUDE-AD is a Phase 2, multi-center, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of sabirnetug. The study drug will be evaluated in approximately 540 adults ages 50 to 90 years. Thus far, the study is enrolling at 75 sites across the US, Canada, EU and U.K. Acumen expects to complete enrollment in the first half of 2025.

One key eligibility criterion in ALTITUDE-AD and other clinical trials for amyloid-targeting therapies is the confirmation of cerebral amyloid accumulation by either PET scan or CSF, which can be more burdensome and time-intensive than a blood biomarker assay. However, plasma concentrations of the biomarker pTau217 are a strong indicator of AD pathology.

While not a diagnostic, the pTau217 assay is being used at US trial sites as an enrichment approach – a first step to help identify potential clinical trial participants with the highest likelihood of having amyloid in the brain as confirmed by a subsequent PET scan or CSF.

The pTau217 assay is an effective tool for classifying participants most likely to be eligible for the ALTITUDE-AD study. The study established a pTau217 threshold of ≥0.15 pg/mL, which was designed for enrichment purposes in this study of early AD and was not intended as a diagnostic cut-point. To date, more than half of potential ALTITUDE-AD study participants have been excluded from the study because of a plasma p-tau217 test result <0.15 pg/mL.

Overall, 74 percent of participants with p-tau217 ≥0.15 pg/mL met study amyloid burden eligibility requirements following confirmatory assessment with amyloid PET scan or CSF Aβ42/40. In contrast, 40 percent of participants met study amyloid burden eligibility requirements in the Phase 1 INTERCEPT-AD trial when amyloid PET was used as the initial screening tool.

“The study is not only a testament to our commitment to advancing a next-generation treatment for Alzheimer’s disease but also our commitment to pioneering clinical trial designs that provide an improved patient experience,” said Daniel O’Connell, President and Chief Executive Officer of Acumen.

“We are pleased with the pace of enrollment in ALTITUDE-AD thus far. This swift progress underscores the strong interest in our approach and desire to bring more innovative solutions to those affected by Alzheimer’s,” O’Connell added.