Johnson & Johnson's Anti-Tau Monoclonal Antibody Posdinemab Receives FDA Fast Track Designation for Early Alzheimer’s Disease

On January 8 local time, Johnson & Johnson announced that its researchTau Monoclonal Antibody Posdinemab Granted Fast Track Designation by U.S. FDA, used for treatmentEarly Alzheimer'sDisease(AD) patients.

Previously, Johnson & Johnson's active immunotherapy JNJ-2056 targeting phosphorylated Tau protein was also granted Fast Track designation by the FDA.

Posdinemab is a monoclonal antibody targeting a specific hyperphosphorylated epitope in the middle region of the Tau protein, which can delay or prevent the progression of AD by inhibiting the pathological deposition and spread of Tau protein. Currently, PosdinemabPhase IIb AuTonomy Clinical Study is Underway（NCT04619420）。

In November 2021, Posdinemab was approved for clinical use in China for the first time to delay cognitive decline in patients diagnosed with prodromal AD and mild AD dementia. The official website of the Drug Clinical Trial Registration and Information Disclosure Platform shows that Johnson & Johnson has completed a Phase I, open-label, single-dose study in Chinese healthy subjects to evaluate the pharmacokinetics, safety, and tolerability of Posdinemab.

▍Current Situation

In the brain neurons of Alzheimer's disease (AD) patients, two major proteins misfold and accumulate into aggregates — Tau protein and β-amyloid (Aβ).In the past few decades, the main therapeutic strategy for AD has focused on the Aβ cascade hypothesis.。

Among the 7 Aβ monoclonal antibodies with relatively fast R&D progress, three have been approved for marketing, namelyEisai/Biogen's AducanumabAndLecanemab (Lunca Nai Monoclonal Antibody)，and Eli Lilly'sDonanemab (Duanemab)。

Among them, Aducanumab has been abandoned by both Eisai and Biogen due to ongoing controversies. Lecanemab is expected to achieve full-year sales of 2 billion yuan in the fiscal year 2024. Donanemab, which has been on the market for less than half a year, shows promising market performance.

▍Tau Protein

Tau Protein is a low molecular weight microtubule-associated protein, the physiological function of which is to enhance the stability of cellular microtubules. Pathological Tau deposition is one of the causes of neurofibrillary tangle (NFT) formation and neuronal loss. Due to reasons such as Aβ deposition, cyclin-dependent kinase-5 becomes overactivated, leading to hyperphosphorylation of Tau protein. This excessive phosphorylation disrupts the Tau-microtubule interaction, reducing the affinity of Tau protein for microtubules and resulting in NFT deposition in the cytoplasm, causing transport defects along microtubules and neuronal death.

With the progress in our understanding of Tau-dependent neurotoxicity and the promising results of Tau immunotherapy in several preclinical studies, Tau-based therapeutic strategies can provide new insights for AD drug development.

The current drug development strategy mainly adoptsInhibiting excessive phosphorylation of Tau protein, controlling the aggregation and spread of pathological Tau, and active and passive immunotherapy.

Compiled from:

Insight Database: "Treating Alzheimer's Disease! Johnson & Johnson's Tau Monoclonal Antibody Granted FDA Fast Track Designation"

Journal of China Pharmaceutical University "Latest Advances in Alzheimer's Disease Drug Development"

Biomarker Research "Nature Reviews Neurology: Current Status and Future of Tau-Targeted Therapy in Alzheimer's Disease"