Alzheimer Vaccine ABvac40 Shows Potential to Slow Cognitive Decline in Phase 2 Study

María Pascual-Lucas, PhD

Results from the AB1601 phase 2 study (NCT03461276) of ABvac40 (Grifols), an investigational vaccine targeting amyloid-ß (Aß), revealed a significant reduction in clinically meaningful cognitive decline, with the strongest effects seen in patients with Alzheimer disease (AD) with the highest antibody levels.¹

The per-protocol cohort (PPc) of the double-blind, placebo-controlled trial comprised 97 patients with mild cognitive impairment or very mild AD, 69 (71.1%) of which were amyloid-PET positive. In the trial, patients treated with the investigational product were stratified by cerebrospinal fluid (CSF) antibody levels in 2 groups: high levels (quartile 4) and low levels (Q1-Q3). After 24 months of treatment, those on ABvac40 had reduced risk of meaningful within-patient changes (MWPC) relative to placebo (HR, 0.47; 95% CI, 0.27-0.85; P = .012).

These data were presented at the 2025 Alzheimer’s Association International Conference (AAIC), held July 27-31, in Toronto, Canada, by María Pascual-Lucas, PhD, senior scientist at Araclon Biotech. In the double-blind study, MWPC was defined as a decline of at least 3 points in Mini-Mental State Exam (MMSE) at two consecutive visits over 24 months. Cox proportional hazards models were used to assess the risk of MWPC, adjusting for MMSE baseline score, baseline age, apolipoprotein E4 carrier status, clinical stage, and baseline use of AD medication.

In the amyloid-PET positive subgroup, ABvac40 showed a more pronounced treatment effect (HR, 0.38; 95% CI, 0.20-0.75; P = .005) in comparison with non-amyloid PET positive patients. Within this subgroup, those with lower antibody levels had a 63% lower risk of MWPC (HR, 0.37; 95% CI, 0.16-0.83; P = .016), while those with higher antibody levels showed an 81% reduction (HR, 0.19; 95% CI, 0.04-0.84; P = .029). Pascual-Lucas et al concluded these data support ABvac40’s potential to influence disease progression and warrant further studies to explore its impact on brain vessels as potential driver of the observed cognitive benefits.

READ MORE: Biogen Showcases Promising 4-Year Data for Alzheimer Therapy Lecanemab at AAIC 2025

Data from the phase 2 study was previously announced in 2023, at the Clinical Trials on Alzheimer’s Disease annual meeting. All told, the trial met its primary end points and showed differences between the vaccine- and placebo-treated groups in some secondary exploratory end points. In the active treatment group, there were no reports of amyloid-related imaging abnormalities-edema or aseptic meningo-encephalo-myelitis, as well as few instances of micro-hemorrhages compared with placebo and none that led to discontinuation.

Other neuropsychological tests, such as the Repeatable Battery for the Assessment of Neuropsychological Status, or the Trial Making Test, showed favorable results on ABvac40 vs the placebo group. Global or functional scales showed no differences between the ABvac40 and placebo groups, although volumetric MRI revealed a lesser increase in whole brain atrophy with ABvac40.

During the meeting, Jose Terencio, PhD, vice president of Innovation and New Technologies at Grifols, sat down with NeurologyLive^® to discuss the study in detail, how it was conducted, and some of the topline results clinicians should key in on. In the video below, he spoke about the neuropsychiatric benefits observed with the vaccine, the its positive safety profile, and why it differs from traditional antiamyloid therapies that have amyloid-related imaging abnormalities associated with them.

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REFERENCES
1. Pascual-Lucas M, Lacosta AM, Montanes M, et al. Meaningful Clinical Impact of ABvac40 in Early-Stage Alzheimer’s Disease: Results from the AB1601 Phase 2 Study. Presented at: AAIC 2025; July 27-31; Toronto, Canada. Abstract 102589.

2. Terencio J, Pascual-Lucas M, Lacosta AM, et al. Safety, immunogenicity, clinical efficacy and biomarkers of ABvac40, an active vaccine anti-Aß40 in patients with amnestic mild cognitive impairment or very mild Alzheimer’s disease: final results of a phase 2 randomized study. Presented at: Clinical Trials on Alzheimer’s Disease (CTAD) conference; October 24-27, 2023; POSTER LB04