Biogen presented at the CTAD conference that aducanumab reduced plasma p-tau181, a biomarker of neuronal injury in Alzheimer’s disease
Neurimmune welcomes news from Biogen that data from approximately 7’000 plasma samples from more than 1’800 patients in the aducanumab Phase 3 clinical trials showed a statistically significant correlation between plasma p-tau reduction and less cognitive and functional decline in patients with Alzheimer’s disease.
Alzheimer’s disease - the leading cause of dementia in elderly people - is characterized by the co-occurrence of amyloid and tau neurofibrillary tangles in the brain. Age-related increases in brain amyloid can trigger a slowly progressing sequence of mildly neurotoxic events and cellular reactions. Aggregated forms of the amyloid beta protein can cause subtle effects on communications between neurons which can lead to damage of neuronal transport systems, abnormally phosphorylated tau such as p-tau181 and the formation of neurofibrillary tangles consisting of abnormally phosphorylated tau proteins. Besides the removal of amyloid, the removal of pathologic tau is a therapeutic objective in Alzheimer’s disease.
In a pre-specified analysis of plasma samples, patients treated with high dose aducanumab showed a decrease of plasma p-tau181 of 21% compared to placebo in the EMERGE Phase 3 study and of 25% compared to placebo in the ENGAGE Phase 3 study. Reductions in plasma p-tau181 were correlated with a lowering of amyloid beta plaques as well as with less decline across all four clinical measures in both studies, namely CDR-SB, MMSE and ADAS-Cog13 measuring cognitive functions and ADCS-ADL-MCI measuring activities of daily living. The new data were presented on Thursday by Oskar Hansson from Lund University at the Clinical Trials on Alzheimer’s Disease conference (CTAD).
“Tau pathology is a reaction of neurons to damage in CNS diseases. In Alzheimer’s disease, tau pathology is triggered by aggregated amyloid beta. The new biomarker data on plasma p-tau181 show that aducanumab mediated removal of amyloid is directly linked to a reduction of biomarkers of neuronal injury. The new data provide substantial evidence for an important link between reduction of brain amyloid, reduction of plasma p-tau181 and the slowing of disease progression”, said Roger Nitsch, CEO of Neurimmune. “The plasma p-tau181 data are also well in line with previous findings from sub-studies measuring pathologic tau by tomography or tau isoforms in brain fluids.”
In Alzheimer’s disease, amyloid deposition precedes the onset of dementia by at least 20 years. The measurement of biomarker trajectories show that amyloid pathology precedes tau pathology. This is evidenced by changes in CSF and plasma levels of amyloid beta 42 and subsequent increases of p-tau in brain fluid and plasma as well as the detection of tau neurofibrillary tangles in brain. At the time of diagnosis of dementia symptoms, amyloid deposition is typically close to its maximum in Alzheimer’s disease.1
Aducanumab is a human monoclonal antibody capable of removing amyloid beta in the brain. The antibody was discovered with Neurimmune’s Reverse Translational MedicineTM technology and licensed to Biogen who co-developed it with Eisai.
1O. Hansson, Nature Medicine, 27, 954-963 (2021)
About Neurimmune
Neurimmune is a biopharmaceutical company translating human immune memory into transformative antibody therapeutics. Neurimmune develops drug candidates for CNS and related protein aggregation diseases including Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, dementia with Lewy bodies and ATTR cardiomyopathy. Neurimmune discovered aducanumab, a human monoclonal antibody targeting aggregated amyloid beta, together with a team of researchers at the University of Zurich and licensed it to Biogen. With its Reverse Translational MedicineTM (RTMTM) technology, Neurimmune also discovered the anti-tau antibody BIIB076 for Alzheimer's disease, the anti-miSOD1 antibody AP-101 for ALS and the anti-ATTR antibody NI006 for ATTR cardiomyopathy, programs being currently evaluated in clinical trials. Neurimmune has three additional antibody programs in preclinical development and has recently expanded the spectrum of its treatment modalities by adding a small molecule program and programs involving vectorized expression of human antibody genes.
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