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Caroline Hroncich was associate editor for Pharmaceutical Technology, Pharmaceutical Technology Europe, and BioPharm International from 2015 to 2017.
In Phase Ib trials, Biogen’s aducanumab reduced amyloid-beta in the brains of patients with Alzheimer’s disease.
Results from a small Phase Ib trial with Biogen’s aducanumab showed the drug's potential as an investigational treatment for patients with Alzheimer’s disease (AD). Researchers from the University of Zurich evaluated the efficacy of aducanumab in 165 patients with early-stage AD. At the conclusion of 54 weeks, the researchers reported seeing a dose-dependent reduction of amyloid-beta in patient’s brains compared to a placebo. Exploratory results indicate the drug may also slow clinical decline.
Amyloid-beta is associated with the development of AD, and its removal, Biogen said in a Aug. 31, 2016 press announcement, is thought to slow clinical decline in patients. Scientists are still unsure whether or not these plaques cause AD, or if they are a side effect of the disease. According to the National Institutes of Health, genetic mutations can increase the production of amyloid-beta in some rare forms of the disease.
Biogen’s monoclonal antibody (mAb) was reported to clear all amyloid deposits in the brains of 21 patients that remained on the highest dose of the drug throughout the entire study, according to Scientific American. The mAb also may slow clinical decline, which was measured using the Clinical Dementia Rating-Sum of Boxes (CDR-SB) and the Mini-Mental State Examination (MMSE), both of which are tests used to assess the stages of dementia in AD patients. The results published in Nature, indicate the mAb penetrated the brain and reduced amyloid-beta in a “time- and dose-dependent manner.” The researchers comment, “considering that it may have taken up to 20 years for [amyloid-beta] to have accumulated to the levels in these patients at study entry, the observed kinetics of [amyloid-beta] removal within a 12-month time period appears encouraging for a disease-modifying treatment for patients with AD.”
But aducanumab does have some measurable side effects. Study participants reported suffering from Amyloid-related imaging abnormalities (ARIA), headache, urinary tract infection, and upper respiratory infection. Side effects of ARIA included oedema and micro-haemorrhage. Stephen Salloway, professor of clinical neurosciences and psychiatry at Brown University, and study author, told Scientific American, scientists caught evidence of ARIA early, and no patients suffered irreversible damage. In future studies, Salloway noted, patients who carry the gene APOEε4, which can increase the risk of ARIA, will most likely be kept at a lower dose of aducanumab.
It is too early to tell if aducanumab will have a significant effect on the lives of patients with AD, and further research is needed to confirm the results of the Phase Ib trial. Biogen says it will begin two global Phase III trials, ENGAGE and EMERGE, which will further assess the mAbs ability to slow cognitive impairment.