FDA Grants Fast Track Designation to Anti-Tau Therapy Posdinemab

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Key Takeaways

Posdinemab, a tau-directed monoclonal antibody, received FDA fast track designation for early-stage Alzheimer's disease treatment, highlighting its potential to slow cognitive decline.
The AuTonomy study uses a plasma biomarker screening tool to evaluate posdinemab's efficacy, focusing on cognitive decline and tau pathology progression over a 104-week period.
Initial findings from the study show a correlation between tau PET levels and cognitive outcomes, particularly in memory-related brain regions.
The fast track designation underscores the urgent need for new Alzheimer's treatments, with JNJ-2056 also receiving fast track status in 2024.

Posdinemab, a monoclonal antibody that targets the mid-domain of Alzheimer disease-specific phosphorylated tau, is currently being investigated in a placebo-controlled phase 2b trial that employs a plasma biomarker as a screening tool.

Bill Martin, PhD

According to a new announcement, the FDA has assigned fast track designation to Johnson & Johnson’s investigational tau-directed monoclonal antibody posdinemab as a potential treatment for patients with early-stage Alzheimer disease (AD). Anti-tau therapies have shown promise in slowing disease progression by addressing tau pathology, a key driver of cognitive decline in later stages of the disease.¹

Posdinemab is currently being investigated in the phase 2b AuTonomy study (NCT04619420), a double-blind, placebo-controlled, randomized, parallel-group, common-close study that it is the first to employ a plasma biomarker as a screening tool. The study, which assesses the effect of 2 doses of posdinemab (low or high dose) or placebo, every 4 weeks over a 104-week treatment period, includes patients with symptomatic AD who meet clinical and plasma phosphorylated (p-tau)217 criteria followed by intermediate levels of tau burden on tau PET.

"As the average age of the global population increases, the number of people impacted by this debilitating progressive disease continues to rise. Alzheimer disease places a substantial emotional and financial burden on patients and their loved ones and has a significant economic and societal impact," Bill Martin, PhD, Global Therapeutic Area Head, Neuroscience, Johnson & Johnson Innovative Medicine, said in a statement.¹ "Posdinemab has the potential to slow the spread of tau pathology in the brain - which may slow cognitive decline. The FDA’s Fast Track designation reflects the urgent unmet need for new treatment options for the millions living with AD."

AuTonomy, an ongoing study, uses change from baseline in Integrated Alzheimer’s Disease Rating Scale (iADRS) Total Score at week 104 as the primary end point. Other secondary measures include change in Alzheimer’s Disease Assessment Scale Cognitive subscale 13-item version total score, Alzheimer's Disease Cooperative Study Activities of Daily Living for Mild Cognitive Impairment (ADCS-ADL MCI), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Index, Clinical Dementia Rating-Sum of Boxes, Neuropsychiatric Inventory, and change in brain tau burden, among others. Notably, the study will also assess change in cerebrospinal fluid (CSF) concentrations of total, free, and bound p217+tau fragments at week 104.

At the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) conference, investigators presented an analysis of AuTonomy, reporting several lessons learned from the screening experience of the study. Among the greatest takeaways, investigators noted that baseline tau PET standardized uptake value ratio (SUVr) was linked to clinical outcomes across multiple brain areas, especially immediate and delayed memory which moderately correlated with brain regions that included the hippocampus.²

The study involved screening 2670 participants across 115 sites, with 523 ultimately selected for inclusion. A plasma p217 tau assay was used before conducting tau PET scans, reducing the need for PET imaging by 48.9%. Among the 809 tau PET scans conducted, 15.2% were excluded due to insufficient tau levels, 16.2% were excluded due to excessively widespread tau, and 68.6% fell within the intermediate tau criteria. The study reported an overall screening failure rate of 80.4%, consistent with initial projections.

Within the intermediate tau PET category, 44.7% of participants were classified as low tau, while 55.3% were classified as high tau. Additionally, baseline tau PET SUVr values showed a correlation with baseline ADAS-Cog13 scores across various regions of interest (rs = 0.35–0.38, P < .01). The strongest correlation between tau PET levels and RBANS immediate memory domain scores was observed in the total cortex region of interest (rs = 0.42, P < .01). At the start of the study, all 522 participants who received at least one dose of the blinded treatment had a screening CDR global score of 0.5.

The fast track designation for posdinemab was the second such designation granted in 2024 for the company’s AD portfolio. The company’s other anti-tau active immunotherapy, JNJ-2056, the first active immunotherapy targeting tau in a preclinical AD population, was also granted fast track designation in July 2024. JNJ-2056 is currently being investigated in the phase 2b ReTain study (NCT06544616), which remains actively enrolling.

REFERENCES
1. Johnson & Johnson’s Posdinemab and Tau Active Immunotherapy Receive U.S. FDA Fast Track Designations for the Treatment of Alzheimer’s Disease. News release. Johnson & Johnson. January 8, 2025. Accessed January 9, 2025. https://www.jnj.com/media-center/press-releases/johnson-johnsons-posdinemab-and-tau-active-immunotherapy-receive-u-s-fda-fast-track-designations-for-the-treatment-of-alzheimers-disease
2. Henley D, Bogert J, Saad ZS, et al. Study design and screening experience from the phase 2 Autonomy trial of anti-p-tau monoclonal antibody posdinemab for early Alzheimer’s disease. Presented at: Clinical Trials on Alzheimer’s Disease conference; October 29-November 1, 2024; Madrid, Spain. ABSTRACT OC12.