Switzerland-based AC Immune SA revealed in an SEC announcement that partner Johnson & Johnson (J&J) has temporarily halted enrollment in the Phase IIb ReTain study evaluating its active immunotherapy, ACI-35.030 (also known as JNJ-2056), for the treatment of preclinical Alzheimer’s disease. The company noted that the pause, initiated by J&J sub Janssen Pharmaceuticals, is voluntary and related to the evaluation of trial aspects such as recruitment rather than any new safety findings.

Developed by AC Immune and licensed to Janssen under a 2015 deal, ACI-35.030 is a first-in-class phosphorylated-tau (pTau) targeted active immunotherapy. Unlike monoclonal antibodies that target amyloid-beta, this vaccine is designed to stimulate a polyclonal immune response against pathological tau proteins, which form the neurofibrillary tangles associated with neuronal death in Alzheimer’s.

Trial specifics

The Phase IIb ReTain trial (NCT06544616) is a randomized, multicenter study assessing the safety and efficacy of ACI-35.030 in subjects with preclinical, pre-symptomatic Alzheimer’s disease. This patient population consists of individuals who show biological markers of the disease but have not yet developed clinical symptoms. While recruitment is currently on hold, AC Immune confirmed that the trial’s pre-specified interim immunogenicity threshold has been met, indicating the vaccine is successfully eliciting the intended immune response.

Research context

The competitive landscape for Alzheimer’s prevention is increasingly focused on both tau and amyloid-beta targets, with several large-scale clinical programs underway:

  • Eli Lilly’s LY3372689, an O-GlcNAcase (OGA) inhibitor in Phase II development, which aims to slow tau aggregation by modifying how the protein is processed in the brain.
  • Eisai and Biogen’s lecanemab (Leqembi), an FDA-approved monoclonal antibody targeting amyloid-beta; while approved for symptomatic early AD, it is being studied in the Phase III AHEAD 3-45 trial for preclinical populations.
  • Prothena’s PRX005, a microtubule-binding region (MTBR)-tau targeting antibody being developed in collaboration with Bristol Myers Squibb, currently in Phase I/II clinical trials.
  • Vaxxinity’s UB-311, a competitive active immunotherapy targeting amyloid-beta that has completed Phase IIa and is being positioned for Phase III.