Posdinemab
| Clinical data | |
|---|---|
| Drug class | Anti-tau protein antibody |
| Identifiers | |
| CAS Number | |
| PubChem CID | |
| DrugBank | |
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| KEGG | |
| ChEMBL | |
| E number | {{#property:P628}} |
| ECHA InfoCard | {{#property:P2566}} |
| Chemical and physical data | |
| Formula | C6570H10188N1730O2085S44 |
| Molar mass | 148182.44 g·mol−1 |
Posdinemab (development code JNJ-63733657) is an investigational monoclonal antibody developed by Johnson & Johnson for the treatment of Alzheimer's disease. It is designed to target phosphorylated tau protein, specifically binding to phosphorylated amino acid 217 (pT217) in the proline-rich domain of tau.[1]
Mechanism of action
Posdinemab is a humanized IgG1/kappa monoclonal antibody that binds with high affinity to phosphorylated amino acid 217 (pT217) in the proline-rich domain of tau protein.[1] The parent molecule, designated PT3, was originally raised against Alzheimer's disease brain-purified paired helical filaments.[1] Preclinical studies with the humanized version have demonstrated reductions in tau seeding, the process by which toxic tau spreads through the brain.[2]
The antibody works by targeting abnormal tau proteins that accumulate in the brains of patients with Alzheimer's disease. Unlike therapies that target amyloid beta, posdinemab specifically addresses tau pathology, which is closely associated with neuronal dysfunction and cognitive decline in Alzheimer's disease.[1]
Clinical development
Phase I studies
The first-in-human clinical trials of posdinemab included both healthy participants and participants with Alzheimer's disease.[1] These Phase 1 studies evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of the antibody. A separate single ascending dose study was also conducted in Japanese participants.[1]
The Phase 1 trials demonstrated no safety or tolerability concerns and showed dose-dependent reductions in phosphorylated tau protein at position 217 (p217+tau) in cerebrospinal fluid following administration of posdinemab.[1] The safety and biomarker profiles from these studies supported the continued investigation of the compound.[1]
Phase II studies
AuTonomy study
Posdinemab is currently being evaluated in a Phase 2b clinical trial called "AuTonomy" (NCT04619420).[3] This study is investigating the efficacy and safety of posdinemab in patients with early Alzheimer's disease, including those with prodromal Alzheimer's disease and mild Alzheimer's dementia.[4]
The AuTonomy study evaluates the effect of two doses of posdinemab (low or high dose) compared to placebo, administered every 4 weeks over a 104-week treatment period.[5] The study includes patients with symptomatic Alzheimer's disease who meet clinical criteria and have elevated plasma phosphorylated tau-217 levels, followed by intermediate levels of tau burden on tau PET imaging.[5] As of August 2025, the Phase 2b AuTonomy study is fully enrolled and ongoing.[4]
This trial represents the first to employ a plasma biomarker approach for participant selection in anti-tau therapy studies.[6]
Regulatory status
Fast Track Designation
In January 2025, posdinemab received FDA Fast Track designation from the U.S. Food and Drug Administration for the treatment of Alzheimer's disease.[2] The Fast Track designation is granted to facilitate the development and expedite the review of drugs that address unmet medical needs in serious conditions.[2]
International development
According to some sources, posdinemab received its first clinical approval in China in November 2021 to delay cognitive decline in patients diagnosed with prodromal Alzheimer's disease and mild Alzheimer's dementia stages, though this information requires verification from regulatory authorities.[7][citation needed]
See also
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Galpern WR, Triana-Baltzer G, Li L, Van Kolen K, Timmers M, Haeverans K, Janssens L, Kolb H, Nandy P, Aida K, Shimizu H, Mercken M, Sun H (2024). "Phase 1 Studies of the Anti-Tau Monoclonal Antibody JNJ-63733657 in Healthy Participants and Participants with Alzheimer's Disease". The Journal of Prevention of Alzheimer's Disease. 11 (6): 1592–1603. doi:10.14283/jpad.2024.163. PMC 11573813 Check
|pmc=value (help). PMID 39559872 Check|pmid=value (help). - ↑ 2.0 2.1 2.2 "Johnson & Johnson's Posdinemab and Tau Active Immunotherapy Receive U.S. FDA Fast Track Designations for the Treatment of Alzheimer's Disease" (Press release). Johnson & Johnson. January 8, 2025.
- ↑ "Study of JNJ-63733657 in Participants with Alzheimer's Disease". ClinicalTrials.gov. NCT04619420. Retrieved 2025-09-22.
- ↑ 4.0 4.1 "Johnson & Johnson showcases latest advancements in Alzheimer's research at AAIC 2025" (Press release). Johnson & Johnson. August 8, 2025.
- ↑ 5.0 5.1 "FDA Grants Fast Track Designation to Anti-Tau Therapy Posdinemab". Neurology Live. January 9, 2025.
- ↑ "Screening Experience of Phase 2 Autonomy Study Provides Insights for Anti-Tau Trials in Alzheimer Disease". Neurology Live. November 6, 2024.
- ↑ "Delving into the Latest Updates on Posdinemab with Synapse". Synapse PatSnap. Retrieved 2025-09-22.
External links
- AuTonomy Phase 2b Clinical Trial at ClinicalTrials.gov
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