Alzheimer Vaccine ABvac40 Results in Lowered Cortical Perfusion Decline

A PET analysis from a phase 2 trial (NCT03461276) showed that use of Araclon’s ABvac40, an anti-amyloid-ß (Aß)40 active immunotherapy, led to reduced cortical perfusion decline in patients with Alzheimer disease (AD). The study authors concluded these findings may be in part because of its vascular effect on amyloid deposition, although more studies are needed to confirm these results.¹

The analysis, presented at the 2025 Clinical Trials on Alzheimer’s Disease (CTAD) Conference, held December 1-4 in San Diego, California, assessed perfusion PET images of patients from baseline, 12 months, and 24 months into the study. All told, patients treated with the AD vaccine demonstrated favorable trends in cortical perfusion, with significant differences at 12 months in the right parietal (P = .0447), right occipital (P = .0476), and left posterior cingulate cortices (P = .0346), indicating less deterioration compared with placebo.

Led by Maria Pascual Lucas, PhD, senior scientist at Araclon Biotech, reduced cortical perfusion decline suggests that a therapy may be helping maintain neuronal activity, vascular integrity, and cognitive function. In addition, treatments that preserve perfusion could potential reduce small vessel disease-related injury, white matter damage, and microinfarcts. Overall, there are several aspects to cortical perfusion decline that are strongly tied with cognition and disease progression.

The analysis presented at CTAD 2025 quantified and defined 20 individual cortical regions using the Automated Anatomical Labeling atlas. Other somewhat favorable trends for ABvac40-treated patients included right temporal (P = .0834) and right visual cortex (P = .0716). Almost all regions showed improved perfusion vs placebo except for left precuneus, the only worsened region, and left occipital, which remained relatively unchanged.

In the study, a voxel-wise analysis with statistical parametric mapping (SPM) was performed to explore regional perfusion differences between baseline and 12-month scans. Here, results confirmed ABvac40’s effect on cortical perfusion, as treated patients (n = 41) exhibited less extensive and less pronounced pattern of perfusion decrease relative to those on placebo (n = 34).

Prior Phase 2 Data

Topline data from the phase 2 study, also known as AB1601, was originally presented at the 2023 CTAD conference. Overall, ABvac40 met its primary end points of safety, tolerability, and immunogenicity, showing a robust immune response against Aß40 and an acceptable safety profile. Although the trial was not powered for efficacy, those on the investigational vaccine demonstrated an almost 38% reduction in disease progression, reflected through Mini-Mental State Exam scores, against placebo.²

Another analysis of the phase 2 study, presented earlier this year at the Alzheimer’s Association International Conference, further highlighted the impact of ABvac40 on cognitive decline. The per-protocol cohort included 97 patients with mild cognitive impairment or very mild AD, 71% of whom were amyloid-PET positive. Treated patients were further stratified by CSF antibody levels into high responders (Q4) and low responders (Q1–Q3).³

All told, treatment with the vaccine led to reduced risk of meaningful within-patient changes (MWPC), defined as a decline of at least 3 points in MMSE across 2 consecutive visits, relative to placebo (HR, 0.47; 95% CI, 0.27-0.85; P = .012). 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).

Phase 1

The clinical path of ABvac40 first started in 2018 with a phase 1, double-blind, placebo-controlled trial of patients aged 50-85 years with mild to moderate AD. In the study, patients were randomly assigned 2:1 to either ABvac40 or placebo, with treatments administered subcutaneously at 4-week intervals.⁴

Overall, ABvac40 demonstrated a favorable safety and tolerability profile while eliciting a consistent and specific immune response. Published in Alzheimer’s Research & Therapy, 71 total adverse events (AEs) were recorded, with higher rates in the placebo group (88%; n = 7) than the ABvac40 group (69%; n = 11; P = .06214). Notably, there were no incidents of vasogenic oedema, sulcal effusion, or microhemorrhages throughout the study period. In total, 11 of the 12 (92%) individuals receiving 3 injections of ABvac40 developed specific anti-Aß40 antibodies.

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REFERENCES
1. Pascual-Lucas M, Lacosta AM, Montañes M, et al. ABvac40 Vaccine Is Associated with Reduced Cortical Perfusion Decline in Early-Stage Alzheimer’s Disease: Results from the AB1601 Phase 2 Study. Presented at: 2025 CTAD Conference; December 1-4; San Diego, CA. ABSTRACT P081.
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
3. 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.
4. Lacosta AM, Pascual-Lucas M, Pesini P, et al. Safety, tolerability and immunogenicity of an active anti-Aβ40 vaccine (ABvac40) in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase I trial. Alzheimers Res Ther. 2018;10(1):12. doi:10.1186/s13195-018-0340-8.