The investigational human monoclonal antibody drug aducanumab (BIIB037) has been shown to reduce amyloid plaque levels in the brain and slow cognitive decline in patients with early or mild Alzheimer’s disease (AD) in an early stage study.
Aducanumab was able to reduce amyloid plaque in all regions of the brain at week 26, with even greater reductions at week 54. The reduction was greater with the 10 mg/kg than the 3 mg/kg dose.
In addition, patients receiving the highest dose of the drug (10 mg/kg) had lower reductions in cognitive impairment scores (2.56 versus 3.14 points for patients on placebo) on the Mini Mental State Examination (MMSE) at 1 year, a statistically significant advantage. On the Clinical Dementia Rating (CDR) scale, another measure of cognition, patients on the highest dose of aducanumab declined by an average of 0.59 points –1.45 points lower than those on placebo.
Investigators said a difference of 1-2 points between scores is considered meaningful. The higher the aducanumab dose the patients took, the less their cognition declined, and the longer they took the drug, the bigger the difference between treated and control groups.
The study, presented at the 12th International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders in Nice, France, included 166 patients with prodromal or mild AD randomized to varying doses of aducanumab or placebo. [AD/PDTM 2015; Abstract 269]
The most common adverse event associated with aducanumab was the presence of amyloid-related imaging abnormalities (mild oedema, effusion) on MRI in patients with the Alzheimer’s-related gene ApoE4. Fifty-five percent of ApoE4 carriers receiving the highest dose of adunucumab developed amyloid-related imaging abnormalities compared with 17 percent for non-carriers.
“This is the first time an investigational drug for Alzheimer’s disease has demonstrated a statistically significant reduction in amyloid plaques as well as a statistically significant slowing of clinical impairment in prodromal or mild disease,” said Dr. Al Sandrock, chief medical officer of Biogen, which makes aducanumab.
“Based on these results, we are advancing aducanumab to phase III trial, with plans to initiate enrolment later this year.”
Aducanumab targets beta amyloid proteins, including soluble oligomers and insoluble fibrils in the amyloid plaques which may play an important role in the development of AD, a disease which currently has no cure.