Aducanumab (BIIB037) is being developed by Biogen as a possible Alzheimer’s disease therapy.

The treatment was originally developed by Neurimmune which, after entering a partnership with Biogen in 2007, granted Biogen the license for future development and commercialization of aducanumab. Since October 2017, Biogen is collaborating with Eisai to advance the clinical studies of aducanumab.

How aducanumab works

Alzheimer’s disease is a progressive neurodegenerative disorder characterized by deposits of protein structures called amyloid plaques and tau tangles in the brain, leading to brain cell death.

Amyloid beta (Aβ) is normally present in the brain as a single protein, or monomer. In Alzheimer’s disease, however, it aggregates into clumps that can disrupt communication between brain cells and cause their death.

Aducanumab is an antibody, a protein designed to interact with a specific target. Developed using Neurimmune’s proprietary Reverse Translational Medicine Platform, it works against Aβ. It preferentially binds to the aggregated Aβ as it targets an epitope (a small section of the protein that the antibody recognizes) that is not normally accessible in the Aβ monomer. Through this interaction, aducanumab reduces the number of amyloid plaques present in the brain.

It is thought that by reducing the amyloid plaques, aducanumab may slow neurodegeneration and reduce disease progression.

Aducanumab in clinical trials

Biogen has sponsored six clinical trials investigating aducanumab in humans.

Three Phase 1 trials, assessing aducanumab in healthy volunteers (NCT02782975) and in Alzheimer’s patients in the U.S. (NCT01397539) or Japan (NCT02434718), have already been completed.

A fourth Phase 1 trial (NCT01677572), called PRIME, is ongoing but no longer recruiting participants. The randomized, double-blind, and placebo controlled trial has enrolled 192 prodromal (pre-dementia) and mild Alzheimer’s patients at 32 sites in the U.S. It aims to assess the safety and effect of aducanumab compared to a placebo on amyloid plaques at different doses. This will be measured through positron emission tomography (PET) imaging.

Interim results from the first 165 patients have been published in the scientific journal Nature. During the first year, 40 patients discontinued treatment; however, those who stopped treatment were spread across the aducanumab and placebo groups. All doses of aducanumab (given as monthly intravenous infusions) were seen to significantly reduce amyloid plaques in the brain in a time- and dose-dependent manner compared to baseline, whereas little to no change was seen in the placebo group after one year. The greatest reduction was seen at the higher doses. Aducanumab also appeared to slow the rate of cognitive decline, measured by change in the clinical dementia rating sum of boxes (CDR-SB) and the mini-mental state examination (MMSE). But the trial was not initially set up to measure this.

Results from the long-term extension part of the PRIME trial were presented at the 2017 Clinical Trials on Alzheimer’s Disease (CTAD) meeting. In total, 143 patients from the initial trial opted to continue in the long-term extension part, where all patients receive aducanumab. This included data from patients who had been on aducanumab for up to three years. Patients given aducanumab have continued to experience a time- and dose-dependent reduction in amyloid plaque levels.

Biogen is also conducting two large-scale randomized, double-blind, and placebo-controlled Phase 3 clinical trials, called ENGAGE (NCT02477800) and EMERGE (NCT02484547), in people with early stage Alzheimer’s disease. ENGAGE aims to enroll 1,350 patients at 187 sites in North America, Australia, Europe, and Asia. EMERGE also aims to enroll the same number of patients at 194 sites in North America, Europe, and Asia. Each study is currently recruiting eligible patients; more information is available by clicking on its respective trial identification number.

Both trials aim to assess the efficacy of aducanumab, given once a month at low and high doses by IV infusion, in treating the symptoms of Alzheimer’s disease. Treatment’s efficacy will be measured by changes from baseline, or study start, in CDR-SB, MMSE, Alzheimer’s disease assessment scale-cognitive subscale 13 items (ADAS-Cog 13), and Alzheimer’s disease cooperative study-activities of daily living inventory mild cognitive impairment version (ADCS-ADL-MCI) score over a 78-week period. The trials are expected to conclude in 2022.

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