FDA Grants Fast Track Designation to Posdinemab for Early Alzheimer Disease

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The US Food and Drug Administration (FDA) has granted Fast Track designation to posdinemab, a phosphorylated tau-directed monoclonal antibody (mAb) being investigated for the treatment of patients with early Alzheimer disease (AD) in the phase 2b AuTonomy study.

“It is hearting to learn that the FDA has granted Fast Track designation to posdinemab, a phosphorylated tau-directed monoclonal antibody for early stages of AD. Hopefully, this new medication will prove to be beneficial in modifying treatment outcomes among individuals with AD. We desperately need more disease modifying medications to treat this serious illness!" Rajesh R. Tampi, MD, MS, DFAPA, DFAAGP, told Psychiatric Times. Tampi is professor and chair of the Department of Psychiatry at Creighton University School of Medicine and Catholic Health Initiatives Health Behavioral Health Services, an adjunct professor of psychiatry at Yale School of Medicine, and a member of the Psychiatric Times editorial board.

Posdinemab, a mAb that targets the mid-domain of AD-specific phosphorylated tau, is designed to bind to pathological phosphorylated tau when it is released from neurons and neutralize it before it can seed to other neurons. The internally discovered compound shows promise in reducing the spread of tau through the brain in both in vitro and in vivo nonclinical studies.

"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," said Bill Martin, PhD, global therapeutic area head of neuroscience at Johnson & Johnson Innovative Medicine.

The Phase 2b "AuTonomy" study investigating posdinemab in participants with early AD is fully enrolled and ongoing (NCT04619420). Posdinemab is the second Fast Track designation granted in 2024 for the Company's AD portfolio.

JNJ-2056, an investigational anti-tau active immunotherapy and the first active immunotherapy targeting tau in a preclinical AD population, was granted Fast Track designation back in July 2024. The phase 2b ReTain trial is actively enrolling and will evaluate JNJ-2056’s potential to help generate antibodies against pathological phosphorylated tau in the hopes of delaying or preventing onset of symptoms and overall progression of the disease.

"As the average age of the global population increases, the number of people impacted by this debilitating progressive disease continues to rise. AD places a substantial emotional and financial burden on patients and their loved ones and has a significant economic and societal impact. At J&J, we envision a future where we can help stop the progression of AD the moment it’s detected," said Martin.

In previous phase 1 studies, investigators commented on posdinemab’s unique qualities and what sets it apart from other potential AD treatments: “There are several characteristics of [posdinemab] that are of interest. While other anti-tau mAbs have failed to show an effect on disease progression in AD, [posdinemab] differs from these other antibodies in that it binds to the proline rich domain in the mid-region of tau rather than the N-terminus. It is known that there is cleavage of tau at the N-terminus, and thus antibodies targeting this region may be less effective in neutralizing tau seeds due to truncation. Moreover, [posdinemab] targets the p217+ epitope. Phosphorylated tau, especially at amino acid 217, has emerged as a biomarker associated with brain amyloid and tau burden supporting its relevance to the disease.”

Stay tuned for more on posdinemab and other AD treatment updates.

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. January 8, 2025. https://www.investor.jnj.com/news/news-details/2025/Johnson--Johnsons-Posdinemab-and-Tau-Active-Immunotherapy-Receive-U.S.-FDA-Fast-Track-Designations-for-the-Treatment-of-Alzheimers-Disease/default.aspx

2. Galpern WR, Triana-Baltzer G, Li L, et al. Phase 1 studies of the anti-tau monoclonal antibody JNJ-63733657 in healthy participants and participants with Alzheimer’s disease. J Prev Alzheimers Dis. 2024;11(6):1592-1603.