ABBV-8E12 (formerly C2N 8E12) is an anti-tau antibody being developed by AbbVie and C2N Diagnostics to treat Alzheimer’s disease and progressive supranuclear palsy (PSP). Both Alzheimer’s and PSP are tauopathies, or diseases marked by the abnormal deposition of tau proteins in the brain.

How ABBV-8E12 works

Beta-amyloid plaque deposit and tau protein aggregates known as neurofibrillary tangles that accumulate in the brain are characteristic of Alzheimer’s. Both these aggregates are thought to be toxic to neurons and cause the symptoms of the disease.

Abnormal tau proteins can ‘infect’ other tau proteins in neighboring neurons, causing otherwise normal tau protein to form tangles and promoting the disease’s spread within the brain. Targeting tau proteins, for this reason, is thought to be a feasible approach — and perhaps one better than targeting beta-amyloids — as tau proteins may be more closely associated with neuronal damage and clinical symptoms.

ABBV-8E12 is a recombinant, humanized anti-tau antibody that recognizes and binds to the abnormal tau aggregates, potentially blocking their spread from neuron to neuron and limiting the severity of the disease.

ABBV-8E12 in clinical trials

Studies done on mice models that express neurofibrillary tangles in their brains showed that ABBV-8E12 (as a mouse version, given as weekly injections in doses of either 10 or 50 mg/kg for three months) was able to significantly reduce the amount of abnormal tau protein, markedly reduce brain shrinking and neuronal loss, and protect mice against cognitive deterioration.

A Phase 1 study (NCT02494024) testing ABBV-8E12’s safety, tolerability and pharmacokinetics (how the body absorbs, metabolizes, and expells a drug) was done on 32 patients with PSP. ABBV-8E12 was found to be safe and tolerable when given as injections directly into the bloodstream at single doses of up to 50 mg/kg.

In the trial, only two severe adverse reactions were observed (one case of headache and another of agitation). There did not appear to be a relationship between the treatment dose and severity or number of adverse events. This study was conducted at 12 clinical sites in the U.S. from July 2015 to August 2016.

A Phase 2 clinical trial (NCT02880956) investigating the efficiency and safety of ABBV-8E12 in Alzheimer’s patients opened in October 2016. The trial, taking place at some 60 sites worldwide, is still recruiting up to 400 people with early stage disease as confirmed by various dementia rating scales and a positive amyloid positron emission tomography (PET) brain scan.

Enrolled Alzheimer’s patients will receive one of three different doses of ABBV-8E12 as an IV infusion, or a placebo, for about two years. The primary aim of this trial is to evaluate the ability of ABBV-8E12 to delay cognitive decline in patients and to record any adverse side effects.

This trial is taking place across the U.S. and Europe, and in Australia and New Zealand. It is scheduled to end in June 2021.

Further details

ABBV-8E12 was granted orphan drug designation by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of PSP in 2015. Orphan drug designation is reserved for therapies that show potential in treating rare diseases.

ABBV-8E12 is also being investigated in a separate Phase 2 clinical trial (NCT02985879) for PSP that began in December 2016 and is set to end in May 2019. Plans are in place to begin an extension Phase 1 study (NCT03413319) in 2018 for ABBV-8E12 in the treatment of PSP.

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