Phase 2 Alzheimer's Trial Reveals Significant Racial Disparities in Patient Screening for Tau-Targeting Therapy
核心洞察
Preliminary data from Johnson & Johnson's phase 2b Auτonomy trial of posdinemab shows Black/African American participants experienced 86.4% screen failure rates compared to 80.5% for White participants and 73.3% for Asian participants.
The most common exclusion criterion was lack of elevated plasma phosphorylated-tau217 concentrations, affecting 35.3% of Black participants versus 38.6% of White and 26.7% of Asian participants.
Black/African American participants were nearly twice as likely to fail clinical criteria for early Alzheimer's disease (搜索) compared to White participants (21.6% vs 12.1%).
Preliminary data from Johnson & Johnson's ongoing phase 2b Auτonomy study evaluating posdinemab (JNJ-63733657) has revealed significant racial disparities in screening outcomes for early Alzheimer's disease (搜索) clinical trials. The findings, presented at the 2025 Alzheimer's Association International Conference in Toronto, show that Black/African American participants experienced substantially higher screen failure rates than other racial groups.
Screening Disparities Across Racial Groups
Among 2,563 participants screened for the trial, 2,040 (79.6%) did not meet eligibility criteria. Screen failure rates were highest among Black/African American individuals at 86.4% (51/59), compared with White participants at 80.5% (1,690/2,100) 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.
Clinical Criteria Challenges
The second most frequent reason for exclusion was not meeting the clinical criteria for early Alzheimer's disease (搜索), which includes evidence of progressive cognitive decline, a Clinical Dementia (搜索) 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%).
Broader Context of Alzheimer's Disparities
These differences potentially reflect broader patterns in Alzheimer's disease (搜索) detection and diagnosis. According to a report from the U.S. Department of Health and Human Services, Black older adults have approximately twice the prevalence of Alzheimer's disease and other dementias compared with non-Hispanic White older adults, while Hispanic older adults have approximately 1.5 times the prevalence.
Despite this higher prevalence, dementia (搜索) 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 screen failure rates observed in minoritized groups.
Posdinemab Mechanism and Trial Design
Posdinemab is a tau-directed monoclonal antibody that binds to the mid-domain of phosphorylated tau (搜索) (p217+tau), a biomarker implicated in the progression of Alzheimer's disease (搜索). 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.
The Auτonomy trial is notably the first to implement a plasma p217tau (搜索) assay as a prescreening tool prior to confirmatory tau PET imaging. This two-step process was designed to improve efficiency and reduce participant burden, with findings from the 2024 CTAD conference showing that it reduced the need for PET imaging by nearly 49%.
Implications for Trial Design
However, the trial's reliance on biomarker thresholds, particularly plasma p217tau (搜索) levels, has implications for enrollment, as this criterion accounted for the most common cause of screen failure 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.
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.
The authors emphasized 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 screen failure data from existing Alzheimer's disease (搜索) trials may help inform on recruiting a diverse study population by furthering understanding of any racial differences in underlying Alzheimer's disease pathophysiology levels or co-morbidities contributing to cognitive impairment," they noted.