Phase 2 Trial of Posdinemab Reveals Racial Differences in Screen Failure for Early Alzheimer Disease

Janice Wong, lead author and senior medical leader in neuroscience at Johnson & Johnson

Preliminary data from the ongoing phase 2b Auτonomy study (NCT04619420) evaluating posdinemab (JNJ-63733657; Johnson & Johnson), an investigational anti–phosphorylated tau monoclonal antibody in development for Alzheimer disease (AD), suggest that Black/African American participants experienced higher screen failure (SF) rates than other racial groups.¹

Among 2563 participants screened for the trial, which enrolls individuals with early symptomatic AD, 2040 (79.6%) did not meet eligibility criteria. Presented at the 2025 Alzheimer’s Association International Conference (AAIC), held July 27–31 in Toronto, Canada, SF rates were highest among Black/African American individuals at 86.4% (51/59), compared with White participants at 80.5% (1690/2100) and Asian participants at 73.3% (206/281).

The most common cause of screen failure across all racial groups was the lack of elevated plasma phosphorylated-tau217 concentrations, a key biomarker required for inclusion. Black/African American participants failed this criterion at a rate of 35.3%, compared with 38.6% for White and 26.7% for Asian participants.¹

The second most frequent reason for exclusion was not meeting the clinical criteria for early AD, which includes evidence of progressive cognitive decline, a Clinical Dementia Rating (CDR) global score of 0.5, and a memory box score of at least 0.5. Notably, Black/African American participants were nearly twice as likely to fail this criterion (21.6%) compared with White participants (12.1%) and had higher rates than Asian participants (18.0%).

These differences potentially reflect broader patterns in AD detection and diagnosis, as racial and ethnic disparities in AD have been consistently documented in epidemiologic studies. According to a report from the U.S. Department of Health and Human Services, Black older adults have approximately twice the prevalence of AD and other dementias compared with non-Hispanic White older adults, while Hispanic older adults have approximately 1.5 times the prevalence.²

Despite this, dementia is less likely to be diagnosed in these populations. One study cited in the report found that only 19.3% of Black participants with probable dementia had received a diagnosis, compared with 31.4% of White participants. These disparities may be shaped by multiple factors, including health care access, symptom interpretation, and referral pathways, and may contribute to elevated SF rates observed in minoritized groups.²

Investigators noted that the small sample size of Black/African American participants (n=59) limits generalizability. However, the findings align with prior concerns about underrepresentation and barriers to trial participation in minority communities.

Posdinemab is a tau-directed monoclonal antibody that binds to the mid-domain of phosphorylated tau (p217+tau), a biomarker implicated in the progression of AD. By targeting this specific form of tau, the drug is thought to disrupt tau aggregation and its spread between neurons, which may contribute to slowing neurodegeneration and cognitive decline. Auτonomy was designed to evaluate the safety and efficacy of posdinemab in individuals with early AD.³

Notably, Auτonomy is the first trial to implement a plasma p217tau assay as a prescreening tool prior to confirmatory tau PET imaging. This two-step process was designed to improve efficiency and reduce participant burden, and findings from the 2024 CTAD conference showed that it reduced the need for PET imaging by nearly 49%.³ However, the trial’s reliance on biomarker thresholds, particularly plasma p217tau levels, has implications for enrollment, as this criterion accounted for the most common cause of SF across all racial groups. These screening strategies, although based in science, may inadvertently contribute to disparities in trial access if underlying biomarker levels differ across populations.

The authors noted that analyzing data by population may help inform more inclusive study designs and highlight potential biological, clinical, or systemic differences that impact trial participation, “Analysis of SF data from existing AD trials may help inform on recruiting a diverse study population by furthering understanding of any racial differences in underlying AD pathophysiology levels or co-morbidities contributing to cognitive impairment.”¹

REFERENCES:
1. Meyer M, Henley D, Bogert J, et al. Analysis of reasons for screen failure by participant race in the Phase 2 Auτonomy study in early Alzheimer's disease. Presented at: Alzheimer’s Association International Conference (AAIC) 2025; July 27–31, 2025; Toronto, Canada. Abstract 100107.
2. U.S. Department of Health and Human Services Assistant Secretary for Planning and Evaluation Office of Disability, Aging and Long-Term Care Policy RACIAL and ETHNIC DISPARITIES in ALZHEIMER’S DISEASE: A LITERATURE REVIEW.; 2014. https://aspe.hhs.gov/sites/default/files/migrated_legacy_files/138596/RacEthDis.pdf
3. Meglio M. FDA Grants Fast Track Designation to Anti-Tau Therapy Posdinemab. Neurology live. Published January 9, 2025. Accessed July 29, 2025. https://www.neurologylive.com/view/fda-grants-fast-track-designation-anti-tau-therapy-posdinemab