Posdinemab · program
Posdinemab for Alzheimer's disease
- Fast Track
Phase 2b AuTonomy study (NCT04619420) of intravenous posdinemab vs placebo in participants with early Alzheimer's disease. The U.S. FDA granted Fast Track designation on 2025-01-08. At a planned interim/data review, posdinemab did not achieve statistical significance versus placebo in slowing clinical decline on the primary integrated Alzheimer's Disease Rating Scale (iADRS) endpoint; Johnson & Johnson announced discontinuation of the AuTonomy study on 2025-11-21 (ClinicalTrials.gov overall status: TERMINATED). Full results were presented at the AD/PD 2026 conference on 2026-03-21, showing no significant difference for either dose at week 104 on the primary endpoint or key secondaries (CDR-SB, ADAS-Cog13, ADCS-ADL-MCI); tau-PET data suggested slowed neurofibrillary-tangle accumulation in high-burden regions. Development in early Alzheimer's disease is discontinued.
Development timeline
- missedAuTonomy Phase 2b full results (AD/PD 2026): posdinemab missed the primary iADRS endpoint - no significant difference for either dose vs placebo at week 104; key secondaries also negative; tau-PET suggested slowed neurofibrillary-tangle accumulation. Program discontinued.↗
- Johnson & Johnson announced discontinuation of the Phase 2b AuTonomy study after posdinemab did not achieve statistical significance versus placebo in slowing clinical decline (iADRS primary endpoint) at a planned review. ClinicalTrials.gov overall status: TERMINATED ('Posdinemab did not achieve statistical significance in slowing clinical decline'). Development in early Alzheimer's disease discontinued.↗
- U.S. FDA granted Fast Track designation to posdinemab for early Alzheimer's disease (announced by Johnson & Johnson).↗
- Phase 2b AuTonomy study (NCT04619420) of IV posdinemab vs placebo in early Alzheimer's disease started; biomarker-driven proof-of-concept with iADRS primary endpoint.
- First-in-human Phase 1, 2-part single/multiple ascending dose study (NCT03375697) in healthy subjects and subjects with prodromal/mild Alzheimer's disease started; completed 2019-12-16 (72 participants). Demonstrated linear PK and dose-dependent reductions in free and total p217+tau in CSF.
Readouts
- 2026-03-21ReportedFull resultsmissedNCT04619420
AuTonomy Phase 2b full results (AD/PD 2026): posdinemab missed the primary iADRS endpoint - no significant difference for either dose vs placebo at week 104; key secondaries also negative; tau-PET suggested slowed neurofibrillary-tangle accumulation. Program discontinued. ↗
Clinical trials in Alzheimer's disease
NCT04619420Phase 2Discontinuedn=523
A Study of JNJ-63733657 in Participants With Early Alzheimer's Disease (AuTonomy)
terminatedefficacyChange from baseline in the integrated Alzheimer's Disease Rating Scale (iADRS / iADRS-MCI) total score at week 104 (primary efficacy endpoint)
Study TERMINATED at a planned interim/data review: posdinemab did not achieve statistical significance versus placebo in slowing clinical decline. ClinicalTrials.gov why-stopped: 'Posdinemab did not achieve statistical significance in slowing clinical decline.' Full results presented at AD/PD 2026 (2026-03-21) showed no significant difference between either the low or high dose and placebo at week 104 on the primary iADRS-MCI endpoint, and key secondaries (CDR-SB, ADAS-Cog13, ADCS-ADL-MCI) were similarly negative; tau-PET suggested slowed neurofibrillary-tangle accumulation in high-burden regions. No exact point estimates or p-values published in accessible sources -> effect_size and p_value null. Outcome 'terminated' because the trial was stopped early (CT.gov status TERMINATED).
NCT03375697Phase 1Completedn=72
A 2-Part Randomized, Placebo-Controlled, Double-Blind, Single and Multiple Ascending Dose Study to Investigate Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-63733657 in Healthy Subjects and Subjects With Alzheimer's Disease
metpharmacodynamicCSF free and total p217+tau (pharmacodynamics / target engagement); safety, tolerability and pharmacokinetics
First-in-human single/multiple ascending dose study: no safety or tolerability concerns identified; linear pharmacokinetics; dose-dependent reductions in free and total p217+tau in cerebrospinal fluid consistent with target engagement. Published in J Prev Alzheimers Dis 2024 (doi 10.14283/jpad.2024.163). No numeric effect size / p-value carried here.
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| Posdinemab IV infusion Low- or high-dose IV infusion every 4 weeks (Phase 2 AuTonomy, NCT04619420). Phase 1: single IV doses 1-60 mg/kg; multiple IV doses on Days 1, 29, 57. | Intravenous | — | t½ 528 h · Tmax 3.6 h |
Mechanism of action
Passive tau immunotherapy. Posdinemab (JNJ-63733657) is a humanized IgG1/kappa monoclonal antibody that binds with high affinity to phosphorylated threonine-217 (pT217) in the proline-rich domain of tau (the MAPT gene product), a phospho-epitope enriched in pathological Alzheimer's tau and in CSF. By binding extracellular pathological phospho-tau, it is intended to neutralize and promote clearance of tau seeds and thereby reduce trans-cellular spread ('seeding') of tau pathology and downstream neurodegeneration. Phase 1 first-in-human studies (NCT03375697) showed linear pharmacokinetics and dose-dependent reductions in free and total p217+tau in cerebrospinal fluid, consistent with target engagement. Despite confirmed target engagement and tau-PET imaging suggesting slowed neurofibrillary-tangle accumulation in high-burden regions, the Phase 2b AuTonomy efficacy study did not show a statistically significant clinical benefit, and the program was discontinued in early Alzheimer's disease. No clean numeric binding affinity (Kd/Ki) for the antibody is published in accessible sources, so affinity is left null.
| Target | Action | Affinity |
|---|---|---|
| Tau (pT217)primaryMAPT | Inhibitor | —ⓘ |
← Full Posdinemab compound page (identity, identifiers, all indications)
Sources
- A Study of JNJ-63733657 in Participants With Early Alzheimer's Disease (AuTonomy) — ClinicalTrials.gov (NIH)
- A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-63733657 in Healthy Subjects and Subjects With Alzheimer's Disease — ClinicalTrials.gov (NIH)
- AD/PD 2026: J&J's anti-tau drug posdinemab fails in early Alzheimer's disease — Clinical Trials Arena
- Johnson & Johnson discontinues AuTonomy Tau-antibody study in AD — Alzheimer Europe
- Johnson & Johnson's Posdinemab and Tau Active Immunotherapy Receive U.S. FDA Fast Track Designations — Johnson & Johnson
- 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 (PMC)