J&J Gets FDA Fast Track Designation for Alzheimer’s mAb, Posdinemab

Editor's note: this story was originally published on BioPharmInternational.com.

FDA has granted fast track designation to Johnson & Johnson (J&J) for posdinemab, an investigational phosphorylated tau-directed monoclonal antibody (mAb) for treating patients with early Alzheimer’s disease (AD), J&J announced on Jan. 8, 2025. Discovered by J&J, posdinemab is in a Phase IIb study (AuTonomy) and has shown potential in targeting disease-associated phosphorylated tau in cerebrospinal fluid (CSF) from AD patients who are being treated. The mAb has also shown an ability to block the development and spread of tau aggregates in non-clinical models of disease.

FDA’s decision on posdinemab marks the second fast track designation granted to J&J in 2024 for its AD portfolio. In July 2024, FDA granted fast track designation to J&J’s anti-tau active immunotherapy, JNJ-2056, which represents the first active immunotherapy that targets tau in a preclinical AD population (1). JNJ-2056 is in a Phase IIb trial (ReTain), which is currently actively enrolling patients. This Phase IIb trial will evaluate the potential of JNJ-2056 to activate the immune system so that it generates antibodies against pathological phosphorylated tau. The goal with this mode of action is to delay or prevent the onset of AD symptoms and, ultimately, 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. Alzheimer’s disease 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 Bill Martin, PhD, global therapeutic area head, Neuroscience, Johnson & Johnson Innovative Medicine, in a company press release (1).

Posdinemab targets the mid-domain of AD-specific phosphorylated tau. The mAb is designed to bind to pathological phosphorylated tau when released from neurons and to neutralize it before it can seed or spread to another neuron. Tau, which is abundant in neurons, has a notorious reputation, which is due to the fact that it is found deposited in cells as fibrillar lesions in many neurodegenerative diseases, especially AD (2). Posdinemab has shown promise in reducing tau seeding, which is the process by which toxic tau spreads through the brain, in both in-vitro and in-vivo non-clinical studies.

“Posdinemab has the potential to slow the spread of tau pathology in the brain—which may slow cognitive decline. [FDA’s] [f]ast [t]rack designation reflects the urgent unmet need for new treatment options for the millions living with AD,” said Martin in the press release.

Meanwhile, JNJ-2056 (formerly ACI-35.030, in collaboration with AC Immune) is an investigational anti-tau active immunotherapy that targets the c-terminal region of pathological phosphorylated tau. This therapy is designed to inhibit the seeding and spreading of pathological tau as well, also with the goal of delaying or preventing the onset of clinical symptoms in preclinical AD. The Phase IIb in which JNJ-2056 is being evaluated includes participants with preclinical AD who have tau pathology in their brains but have not yet developed cognitive impairment.

References

1. Johnson & Johnson. Johnson & Johnson’s Posdinemab and Tau Active Immunotherapy Receive US FDA Fast Track Designations for the Treatment of Alzheimer’s Disease. Press Release. Jan. 8, 2025.
2. Stoothoff, W. H.; Johnson, G. V. W. Tau Phosphorylation: Physiological and Pathological Consequences. Biochimica et Biophysica Acta (BBA)—Molecular Basis of Disease 2005, 1739 (2–3), 280-297. DOI: 10.1016/j.bbadis.2004.06.017