Vaccine Candidate Shows Promise for Slowing Cognitive Decline in Mild Alzheimer Disease

UB-311 is an anti-amyloid-β (Aβ) active immunotherapeutic synthetic peptide vaccine that is being investigated for use in individuals with mild Alzheimer disease (AD).^1,2 The vaccine candidate has shown to be well-tolerated with a durable antibody response in a previous phase 1 trial, with new results from a phase 2a study (NCT02551809) that support the continued development of the vaccine, according to results published in eBioMedicine.¹

In the phase 2a study, investigators aimed to determine the safety, immunogenicity, and preliminary efficacy of UB-311 for the targeted population.¹

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The 78-week study was a randomized, double-blinded, placebo-controlled study conducted in Taiwan. Participants were randomized to receive 7 intramuscular injections of UB-311 (Q3M arm), 5 doses of U311 with 2 doses of the placebo (Q6M arm) or 7 doses of the placebo (placebo arm). Between December 7, 2015, and August 28, 2018, there were 43 patients randomized 1:1:1 across the 3 groups.¹

The primary endpoints of the study included safety, tolerability, and immunogenicity of the vaccine, with safety being assessed in all individuals who received at least 1 dose of the vaccine.¹

The study authors reported that UB-311 was safe, well-tolerated, and had a robust immune response. According to the results, there was a 97% antibody response rate and a maintained 93% response by the end of the study in both UB-311 arms.¹

Additionally, there were 3 treatment-emergent adverse events (TEAEs) with the highest incidence: injection-site pain (16%), amyloid-related imaging abnormality with microhemorrhages and hemosiderin deposits (14%), and diarrhea (12%).¹

In the previous phase 1 study, investigators reported that the vaccine candidate was constructed with 2 synthetic Aβ1-14-targeting peptides that were linked to helper T-cell peptide epitopes.²

Before human trials, investigators used hAPP751 transgenic mouse models to determine the proof-of-concept study, and baboons and macaques were used for data on preclinical safety, tolerability, and immunogenicity. In the phase 1 study, investigators administered 3 doses of UB-311 intramuscularly at weeks 0, 4, and 12 to individuals with mild-to-moderate AD. They monitored the individuals until week 48.²

The results indicated that UB-311 has a strong immune response with a high responder rate. Investigators reported that the levels of Aβ1-14 oligomers, protofibrils, and plaque load in the mouse models were reduced. Investigators added that the vaccine candidate was generally safe and well-tolerated in all animal species included in the study.²

Among patients, investigators reported that the vaccine induced a 100% responder rate. The most common TEAEs were injection site swelling and agitation, according to the results of the study.²

Due to the slower rate of increase in Alzheimer's Disease Assessment Scale-Cognitive Subscale from baseline to week 48, investigators concluded that the vaccine candidate had the potential for cognitive improvement among those in the early stages of AD. The results supported and prompted the phase 2a trial.²

According to additional information listed for the study, there are 4 other vaccine candidates for immunotherapy targeting Aβ in clinical development. These include: ABvac40, currently in a phase 2 trial; ACI-24, in phase 1b/2; AZL-101 in phase 1; and ALZN002 in phase 1/2a.¹

There were 4 other candidates discontinued in phase 2 trials due to safety concerns (AN1792), lack of clinical effects (Affitope AD02, ACC-001), or poor immunogenicity (ACI-24), and 1 discontinued due to lack of clinical effect in a phase 3 trial (CAD-106).¹

References

1. Yu HJ, Dickson SP, Wang PN, Chiu MJ, et al. Safety, tolerability, immunogenicity, and efficacy of UB-311 in participants with mild Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase 2a study. EBioMedicine. 2023;94:104665. doi:10.1016/j.ebiom.2023.104665

2. Wang CY, Wang PN, Chiu MJ, et al. UB-311, a novel UBITh amyloid β peptide vaccine for mild Alzheimer's disease. Alzheimers Dement (N Y). 2017;3(2):262-272. doi:10.1016/j.trci.2017.03.005