Biologic · Posdinemab

Posdinemab

DiscontinuedJohnson & Johnson (JNJ)
  • Fast Track

Humanized IgG1/kappa anti-phospho-tau monoclonal antibody (development code JNJ-63733657) that binds with high affinity to phosphorylated threonine-217 (pT217) in the proline-rich domain of tau (MAPT). Designed as a passive tau immunotherapy to bind and clear/neutralize pathological extracellular phospho-tau and reduce trans-cellular tau seeding/propagation in Alzheimer's disease. Developed by Johnson & Johnson (Janssen). Development in early Alzheimer's disease was discontinued in November 2025 after the Phase 2b AuTonomy study failed to show a statistically significant effect on clinical decline.

Also known as: Posdinemab, JNJ-63733657, 2517973-04-3

Data current as of

Key facts

Modality
Biologic
Chemical class
monoclonal antibody, IgG1 antibody
Mechanism
Tau (pT217) inhibitor
Highest phase
Discontinued
Lead indication
Alzheimer's disease
Developer
Johnson & Johnson (JNJ)
Designations
Fast Track
Trials
2 tracked · 129 sites

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.

TargetActionAffinity
Tau (pT217)primaryMAPTInhibitor—ⓘ

Formulations#

FormulationRouteRegimenPharmacokinetics
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

Development timeline#

20182020202220242026TodayPhase 122 Dec 2017 — phase change — 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.Phase 28 Jan 2025 — phase change — U.S. FDA granted Fast Track designation to posdinemab for early Alzheimer's disease (announced by Johnson & Johnson).6 Jan 2021 — phase change — 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.Discontinued21 Mar 2026 — readout (missed) — 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.21 Nov 2025 — phase change — 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.
Phase change Readout Event UpcomingHover a marker for details.
DiscontinuedNov 2025 – Mar 2026
  1. 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.↗
  2. 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.↗
Phase 2Jan 2021 – Jan 2025
  1. U.S. FDA granted Fast Track designation to posdinemab for early Alzheimer's disease (announced by Johnson & Johnson).↗
  2. 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.
Phase 1Dec 2017
  1. 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.

Posdinemab for Alzheimer's disease#

DiscontinuedDiscontinuedAlzheimer's disease indication →

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.

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#

NCT04619420Phase 2Discontinuedn=523

A Study of JNJ-63733657 in Participants With Early Alzheimer's Disease (AuTonomy)

Started Jan 2021· Primary completion Oct 2025· 122 sites across 10 countries

United StatesJapanSpainFrance

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

Started Dec 2017· Primary completion Dec 2019· 7 sites across 4 countries

GermanySpainBelgiumNetherlands

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.

Sources#

  1. A Study of JNJ-63733657 in Participants With Early Alzheimer's Disease (AuTonomy) — ClinicalTrials.gov (NIH)
  2. 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)
  3. AD/PD 2026: J&J's anti-tau drug posdinemab fails in early Alzheimer's disease — Clinical Trials Arena
  4. Johnson & Johnson discontinues AuTonomy Tau-antibody study in AD — Alzheimer Europe
  5. Johnson & Johnson's Posdinemab and Tau Active Immunotherapy Receive U.S. FDA Fast Track Designations — Johnson & Johnson
  6. 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)