Alzheimer’s disease is a common neurodegenerative condition with an increasing social and healthcare burden worldwide, yet treatment options remain limited. Because the disease is chronic and progressive, there is a clear need for safe, sustainable therapies that can be administered over the long term. In this context, active immunisation is a particularly promising approach: it may generate a durable immune response while offering a profile that is potentially more accessible and scalable for broad patient populations. At Araclon Biotech, we are developing active immunisation for Alzheimer’s disease, combining scientific innovation with a strong focus on safety and clinical efficacy.
ABvac40 is an active immunisation therapy targeting the Aβ40 peptide for the treatment of Alzheimer’s disease.
What is ABvac40?
ABvac40 is a therapeutic vaccine designed to induce an immune response against the Aβ40 peptide. It comprises three components, each with a specific role and set of advantages:
Why Aβ40?
The accumulation of amyloid beta (Aβ) peptides, particularly Aβ40 and Aβ42, in the brain is one of the main pathological hallmarks of Alzheimer’s disease. Against this backdrop, ABvac40 offers a different approach from other anti-amyloid therapies.
Unlike strategies aimed at aggregated Aβ42 in the cerebral parenchyma, ABvac40 targets Aβ40 and therefore focuses on amyloid deposits in the walls of cerebral blood vessels. This allows it to act directly on cerebral amyloid angiopathy (CAA), a vascular pathology present in more than 80% of people with Alzheimer’s disease (1) and considered an important contributor to clinical progression (2–6).
CAA has also been identified as a risk factor for amyloid-related imaging abnormalities (ARIA) associated with approved monoclonal antibodies for Alzheimer’s disease (7), further supporting the rationale for therapies that target this vascular component.
In vitro studies have shown that antibodies induced by ABvac40 are highly specific for Aβ40 and can recognise the peptide in different aggregation states (8), supporting its proposed mechanism of action.
1 Jakel et al., Alzheimers Dement 2021. 2 CFAS NGoM, Lancet 2001. 3 Pfeifer et al., Neurology 2002. 4 Arvanitakis et al., Ann Neurol 2011. 5 Boyle et al., Neurology 2015. 6 Vidoni et al., Neurodegener Dis 2016. 7 Greenberg et al., Nat Rev Neurol 2025. 8 Lacosta et al., Alzheimers Res Ther 2018.
Active immunotherapy
As an active immunotherapy, ABvac40 may address several limitations of passive immunotherapies, including the need for frequent infusions, regular magnetic resonance imaging (MRI) monitoring, and high administration costs. It therefore offers a potentially more accessible and sustainable long-term alternative.
Phase I
In the randomised, double-blind, placebo-controlled phase 1 study AB1203, 24 patients with mild to moderate Alzheimer’s disease received subcutaneous doses of ABvac40 or placebo at 4-week intervals (16 ABvac40, 8 placebo). Dosing schedules comprised two half doses, two full doses, or three full doses. The primary objective was to assess safety and tolerability, with immunogenicity, measured by specific anti-Aβ40 antibodies, assessed as a secondary endpoint. ABvac40 showed a favourable safety profile, with no neuroimaging-related adverse events, including vasogenic oedema, sulcal effusion, or microhaemorrhages. In addition, 92% of patients who received three doses developed specific antibodies, demonstrating a consistent and targeted immune response. These findings supported the progression of ABvac40 into later-stage clinical development.
Phase II
In the multicentre, randomised, double-blind, placebo-controlled phase 2 study AB1601, 124 patients with amnestic mild cognitive impairment or very mild Alzheimer’s disease received five monthly injections plus a booster at 10 months, with follow-up continuing for 18 to 24 months. The trial primarily evaluated safety, tolerability, and immunogenicity, while secondary assessments included further markers of immune response, neuropsychological changes, and disease biomarkers. ABvac40 showed a favourable safety profile: the incidence of adverse events was comparable with placebo (90.6% vs 93.3%), as was the incidence of serious adverse events (26.6% vs 26.7%). For amyloid-related imaging abnormalities (ARIA), the main adverse effect associated with recently approved immunotherapies, rates of ARIA-H were similar between groups (12.5% ABvac40; 15% placebo), with no ARIA oedema or meningoencephalomyelitis reported. The vaccine also induced a specific and sustained immune response in plasma, with antibodies detectable in cerebrospinal fluid. In ex vivo studies, these antibodies bound to amyloid deposits in the walls of cerebral vessels, a hallmark of CAA, confirming their ability to recognise the therapeutic target. Exploratory efficacy outcomes also showed favourable trends for ABvac40 on cognitive scales, while magnetic resonance imaging indicated less progression of global brain atrophy. Overall, these findings support the continued development of ABvac40 in later clinical phases.
The phase 2 study was followed by an 18-month extension, allowing long-term safety and immunological memory to be assessed over a total follow-up period of up to 42 months. ABvac40 maintained a favourable safety and tolerability profile and a specific, durable immune response. This response was boosted after a delayed booster dose, reaching antibody levels up to four times higher than those observed during the initial phase.
Early Diagnosis
We are pioneers in the development of assays based on the determination of amyloid peptides in plasma.
How can we help you?
Contact the Araclon Biotech team.