Lausanne-based neurodegenerative disease specialist AC Immune SA and its commercialization partner Janssen Pharmaceuticals Inc/J&J have received Fast Track designation from the US Food and Drug Administration (FDA) for their phosphorylated-tau-targeted Alzheimer’s disease vaccine ACI-35.030/JNJ-2056, providing the opportunity to expedite development and market approval in the US. The FDA designation has led to a potential pivotal trial, the ReTain Phase 2b proof-of-concept study, which has just started enrolling asymptomatic patients and is expected to produce results in 2029.
According to Andrea Pfeiffer, PhD, CEO of AC Immune, a previous Phase Ib/IIa study has demonstrated target specificity for ACI-35.030//JNJ-205, derived from AC Immune’s SupraAntigen platform and licensed by Janssen Pharmaceuticals parent company Johnson & Johnson (J&J) in 2015. ReTain is designed to test the hypothesis that JNJ-2056 has disease-modifying effects to delay or prevent the onset of cognitive impairment and other clinical symptoms in preclinical AD patients by inhibiting the seeding and spread of pathological tau. The study will enroll approximately 500 cognitively normal, tau-positive subjects randomized 1:1 to a single dose level of JNJ-2056 or placebo, administered intramuscularly for up to four years. The primary endpoint measures cognitive decline as assessed by the Preclinical AD Cognitive Composite Score 5 (PACC-5). The key secondary efficacy endpoint will evaluate the effect of JNJ-2056 compared to placebo on the propagation and/or accumulation of tau pathology, as measured by tau PET imaging.
Intact tau protein is a cytoplasmic microtubule-associated protein that binds to microtubules (a component of the cytoskeleton) and participates in their correct assembly. Excessive phosphorylation (hyperphosphorylation) of tau can lead to uncontrolled aggregation of the protein. This results in so-called neurofibrillary tangles (also called Alzheimer fibrils), which can be detected in Alzheimer’s disease and other tauopathies. As part of dementia diagnosis, levels of total tau, phosphorylated tau and beta-amyloid in cerebrospinal fluid are measured.
