To be clear, there’s no solid evidence yet that United’s UB-311 candidate has an impact on cognition and memory in Alzheimer’s patients yet. Nevertheless, the lack of serious side effects is a big step forward in a vaccine development effort that extends back almost 20 years.
Top-line data from the 42-patient study show that the synthetic peptide vaccine – which targets beta amyloid – was well-tolerated in subjects mild Alzheimer’s disease at the two doses studied, and also stimulated anti-amyloid antibodies in 96% of patients – meeting the two primary objectives.
There was also trends towards improvement on all secondary measures, including amyloid deposits in the brain measured using PET, as well as Alzheimer’s symptoms using scales such as the Alzheimer’s Disease Assessment Scale-Cog (ADAS-Cog) and Mini Mental State Examination (MMSE).
Those early signs are encouraging, although the company isn’t suggesting there is evidence of an efficacy signal yet, but the absence of toxicity means that UB-311 is on course to put that to the test in large-scale studies.
An early anti-amyloid vaccine called AN-1792 from Johnson & Johnson was put into clinical trials in the 2000s, but was abandoned after it emerged it caused dangerous T-cell mediated brain inflammation in a minority (6%) of recipients.
Since then, efforts have focused on trying to find vaccines that can stimulate amyloid-binding antibodies without triggering the immune response that causes inflammation, and UB-311 is one result of that drive.
United’s chief executive Mei Mei Hu said that the early results "suggest a clinical response and support the continued and rapid development of UB-311," although the company hasn’t yet revealed what its next steps are in terms of clinical development, and whether it will take the programme forward on its own or seek a partner.
In the meantime, subjects from the phase IIa study will roll over into a long-term extension study and will be offered continued treatment with UB-311.
Additional results, including future analysis of secondary endpoints and other data, will be presented at an upcoming medical meeting, and United is hoping that could be at the International Conference on Alzheimer’s and Parkinson’s Diseases in Lisbon, Portugal, in March.
Other active immunotherapy candidates in trials include Novartis’ CAD106 in phase II/III testing, Araclon Biotech’s ABvac40 in phase II, AC Immune’s ACI-24 in phase I/II, and Lundbeck/Otsuka’s Lu AF20513 in phase I.
All the vaccines are based on the promise that accumulation of beta amyloid is a core pathology in Alzheimer’s disease, forming fibrils and plaques that cause neurons to degenerate and disrupt neural networks.
Of course, there is a chance that this novel way of addressing amyloid build-up in Alzheimer’s will go the same way as dozens of other amyloid-busting drugs that have failed in later-stage testing, and led to speculation in some circles that targeting amyloid may simply not be an effective strategy.
Some amyloid-directed drugs such as Biogen and Eisai’s BAN2401 and Roche/Genentech’s crenezumab are still going through trials, mainly on the premise that giving them earlier in the course of the disease might unlock their potential. Vaccines could feasibly be given to healthy people long before the onset of the disease, and that’s one reason why the active immunotherapy strategy has continued to be pursued despite the early setbacks.
Meanwhile, attention is also turning to other targets, including tau protein, which forms the neurofibrially ‘tangles’ that along with amyloid plaques are hallmarks of Alzheimer’s disease.
There are two tau-targeting vaccines in trials, namely Axon Neurosciences’ AADvac-1 in phase II with results due in 2020, and J&J/AC Immune’s ACI-35 in phase I.
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