Johnson & Johnson (J&J) has discontinued the Phase 2b AuTonomy trial evaluating its tau-targeted monoclonal antibody posdinemab (JNJ-63733657) in early Alzheimer’s disease (AD), according to a press release. The decision followed an interim review indicating that the antibody did not achieve statistical significance in slowing clinical decline.
Posdinemab, developed internally by J&J, targets disease-associated phosphorylated tau (pTau) with the aim of neutralizing extracellular tau “seeds” and preventing the spread of pathological aggregates across the brain. The AuTonomy study began in 2021 at sites across North America, Europe, Australia, and Japan and enrolled more than 520 patients with mild AD. AllSci data indicates the antibody first entered human trials in 2017, while the U.S. FDA granted a fast-track designation earlier this year.
J&J stated that the results “underscore the deep complexity of the disease,” and said it plans to share full findings with the scientific community.
The company maintains a significant presence in AD through its second tau-directed program, JNJ-2056, an active pTau vaccine designed to elicit broad, durable antibody responses against pathological tau. That candidate is also in Phase 2b but is being tested in preclinical AD, targeting cognitively normal but tau-positive individuals in an effort to delay or prevent symptom onset. J&J is developing tau-based diagnostics alongside the program through its partnership with AC Immune, the co-developer and originator of JNJ-2056.
Phase 2 failures highlight complexity of tau targeting
Drug developers continue to pursue a wide range of direct and indirect strategies aimed at interrupting tau phosphorylation, aggregation, and propagation. Several tau-targeted agents remain in mid- or late-stage development, including Eisai’s etalanetug (Phase 2/3), Biogen’s antisense drug BIIB080 (Phase 2), and Bristol Myers Squibb’s BMS-986446 (Phase 2).
However, attrition in the field remains high. UCB/Roche’s bepranemab and Eli Lilly’s LY3372689 are among multiple programs that have recently failed to demonstrate clinical benefit in Phase 2. Analysis using AllSci’s AERIS engine highlights several leading hypotheses for repeated failures, including targeting the wrong tau species or epitopes , translational gaps between animal models and human disease , and the difficulty of demonstrating efficacy in heterogeneous patient populations with varied tau-pathology trajectories.