AbbVie and partner C2N have started clinical trials of an antibody targeting tau proteins that has just been granted orphan drug status by the US FDA.
The first-in-class therapy – called C2N-8E12 or ABBV-8E12 – is being tested in patients with the rare neurodegenerative disorder progressive supranuclear palsy (PSP), which affects around 20,000 people in the US.
Aggregation of tau proteins into ‘tangles’ is a feature of a number of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, and seems to strongly correlate with clinical disease progression. The protein class is abundant in the central nervous system and seems to play a role in stabilizing structures in nerve cells.
AbbVie and C2N entered into a worldwide licensing agreement earlier this year for the development of a portfolio of anti-tau antibodies for the treatment of Alzheimer’s disease and other neurological disorders.
The phase I study is a single ascending dose trial that will evaluate the safety, tolerability and pharmacokinetics of C2N-8E12 in an estimated 32 individuals with PSP, which causes symptoms such as a loss of balance, visual disturbances, slowed movements, and – in advanced cases – behavioural and cognitive changes.
The trial is due to complete next June and will primarily test the safety and tolerability of the antibody, although it will also look at secondary outcomes including immunogenicity of the antibody.
“We are encouraged by the preclinical data of anti-tau antibodies and are committed to exploring the potential of this class of molecules,” said Jim Sullivan, vice president, pharmaceutical discovery, at AbbVie.
Working on PSP gives AbbVie and C2N an opportunity to test the potential of the approach in a disease for which it will be easier to show efficacy, whilst also working exploring its potential other more common neurodegenerative diseases – such as Alzheimer’s disease – that require years of study to gauge any impact.
Most therapeutic development in the area of Alzheimer’s has focused on the amyloid plaques that characterise the disease, but a series of disappointing trial results have caused researchers to look at different drug targets, and tau has emerged as an interesting option.
Later this week both Eli Lilly and Biogen are due to report clinical data on anti-amyloid candidates at the Alzheimer’s Association International Conference (AAIC), which starts on Saturday in Washington, DC.
Other companies working on tau as a target include TauRx Therapeutics, which has a phase III trial ongoing of its lead candidate LTX in Alzheimer’s and is due to report results early next year.
Axon Neuroscience has started trials of a vaccine directed against tau protein in Alzheimer’s, while Johnson & Johnson’s Janssen subsidiary has also partnered with AC Immune on another tau-targeting vaccine candidate called ACI-35. Last year, Bristol-Myers Squibb bought into the field via a $725m deal to acquire iPierian.
Meanwhile, Biogen licensed rights to a tau-targeting compound in development at Eisai for Alzheimer’s in March, while Astellas signed a $1.2bn agreement with Proteostasis Therapeutics last November that covers a range of protein folding diseases and also covers tau research.