Antibody discovered by Zurich University spin-out shows positive effect in Alzheimer’s disease

An antibody therapy discovered by Zurich University spin-out Neurimmune Therapeutics has been shown to reduce amyloid beta deposits in the brains of patients with mild Alzheimer’s disease.

A paper published today in the science journal Nature (1 September), presents preclinical data and the results of an initial Phase Ib clinical trial, which the authors say support the further development of the antibody as an amyloid beta-removing, disease-modifying therapy for Alzheimer’s disease.

Amyloid deposits in the brain are the hallmark of the disease and amyloid beta-related toxicity is thought to be a primary cause of the neurodegeneration that underlies the characteristic progression of Alzheimer’s. However, previous attempts to target amyloid beta therapeutically have been unsuccessful.

Roger Nitsch, co-founder and president of Neurimmune, and researchers from the US biotech company Biogen Idec, which licensed the rights to the product, aducanumab, in 2007, report that it selectively targets and neutralises amyloid beta protein in the brain.

In a transgenic mouse model, the authors show that aducanumab can enter the brain and dose-dependently reduce soluble and insoluble amyloid beta.

The authors also conducted a double-blind, placebo-controlled Phase Ib randomised clinical trial to evaluate the safety and tolerability of monthly aducanumab injections in patients with mild cognitive impairment or mild dementia due to AD and with brain amyloid beta deposits.

In total, 165 patients received monthly infusions of either placebo or aducanumab for one year. After 54 weeks of treatment, amyloid beta was significantly reduced in the brains of patients who received aducanumab and higher doses were associated with greater amyloid reduction. There was little change in the brains of those who received the placebo.

Higher antibody doses and greater amyloid beta plaque reductions were also associated with slower cognitive decline.

However, the study was not designed to definitively address aducanumab’s impact on cognitive decline and Biogen is now trying to confirm the clinical effects of the antibody in two large phase III studies, which will recruit 2,700 patients. The studies began in September 2015, triggering a milestone payment of $60 million from Biogen to Neurimmune.

Previously, other anti-amyloid antibodies have been shown to reduce levels of amyloid deposits in phase I and phase II, but did not show a significant impact on cognitive decline in phase III.