COMMENTARY

Aducanumab's Promise in Early Alzheimer's

Hans-Christoph Diener, MD, PhD

Disclosures

October 10, 2016

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Dear colleagues, welcome. I'm Christoph Diener, a retired neurologist at the University of Essen in Germany, but I still hold a job as senior professor of clinical neurosciences, which means that I screen the literature. Today I'm reporting on one of the most exciting papers I have seen in the past 5 years: a study on Alzheimer disease, published in the September issue of Nature.[1]

It is well known that we don't presently have a treatment for Alzheimer disease, though this might change. This study investigated the monoclonal antibody aducanumab against amyloid plaques in the brain. As amyloid experiments have shown, this antibody is able to cross the blood-brain barrier and get into the brain. In mice, it removed not only beta amyloid but also tangles.

Between 2012 and 2014, investigators performed a study in the United States in 163 initial patients with mild Alzheimer disease, with 125 patients available for the final analysis. Patients were recruited by amyloid PET and therefore had to have an amyloid lapse in the brain. They were then treated in the dose-finding study with one monthly infusion of 1, 3, 6, or 10 mg of the antibody aducanumab per kilogram of body weight. The outcomes were measured at 26 and 54 weeks, with the investigators looking at the amyloid plaque content using PET imaging. They also performed a cognitive scale and a mini mental state examination.

The study's outcome was a big surprise: In a time- and dose-dependent manner, the antibody resulted in a significant decrease in amyloid in the treated patients. In patients who received the highest aducanumab dose for up to 1 year, there was a dramatic decrease in the amount of amyloid plaques in the brain. In parallel, there was also a slowing of cognitive deterioration. Patients in the highest-dose group had almost no change in cognition across 1 year, whereas those in the placebo group showed a clear deterioration.

Only a small number of patients participated in this proof-of-concept study, with an ongoing phase 3 program currently enrolling a much larger population of patients with mild Alzheimer disease. I think the past has shown that if you have moderate to severe Alzheimer disease, it's too late to intervene with any type of pharmacologic treatment.

Ladies and gentlemen, this is dramatic news. If this drug really works, we would for the first time have a way to treat Alzheimer disease, but we have to wait until we see the outcome of the phase 3 trials.

Dear colleagues, I'm Christoph Diener, a neurologist from the University of Essen in Germany. Thank you very much for watching and listening.

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