Drug Development.

Area of Science:

• Neurology and Clinical Trials
• Biomarker Discovery and Validation

Background:

• Alzheimer's disease (AD) clinical trials often exclude individuals lacking amyloid pathology, leading to high screen failure rates.
• Previous studies, like INTERCEPT-AD, showed significant screen failures due to negative amyloid positron emission tomography (PET) scans.
• Plasma pTau217 concentrations are highly predictive of AD pathology, offering a potential screening tool.

Purpose of the Study:

• To evaluate the utility of plasma pTau217 measurement in the ALTITUDE-AD study for enriching participants with sufficient amyloid burden for early AD trials.
• To assess the impact of pTau217 screening on reducing costs and participant burden associated with confirmatory amyloid PET or cerebrospinal fluid (CSF) testing.

Main Methods:

• ALTITUDE-AD (NCT06335173) is a Phase 2 study involving individuals with early AD and amyloid pathology.
• Screening at North American sites included a two-part process: plasma pTau217 testing (Fujirebio Lumipulse assay) followed by confirmatory amyloid PET or CSF Aβ42/40 testing for those with pTau217 ≥0.15 pg/mL.
• Cost analysis compared the two-part screening strategy with projected costs without pTau217 use.

Main Results:

• 48% of screened participants had plasma pTau217 ≥0.15 pg/mL, qualifying for confirmatory testing.
• 81% of participants with elevated pTau217 met amyloid eligibility criteria via PET or CSF.
• The pTau217 screening strategy reduced total screening costs by approximately US $10 million (40%) at US and Canadian sites.

Conclusions:

• Plasma pTau217 screening effectively enriches early AD clinical trials for participants meeting amyloid-based inclusion criteria.
• This approach significantly reduces screening costs and minimizes invasive procedures like lumbar punctures and radiation exposure from PET scans for potential participants.