FDA Grants Fast Track Designation to Posdinemab

FDA Grants Fast Track Designation to Posdinemab for Early Alzheimer Disease

The US Food and Drug Administration (FDA) has granted Fast Track designation to posdinemab (JNJ-63733657), 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.

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.

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.”