AbbVie has started phase II trials of a drug that binds to tau protein, which for years has played second fiddle to amyloid as a target for new Alzheimer’s disease drugs.
The antibody – called ABBV-8E12 – is being tested in two phase II trials, one in patients with early Alzheimer’s and a second in progressive supranuclear palsy (PSP), a rare neurodegenerative condition that can cause problems with balance, movement, vision, speech and swallowing.
Tau protein occurs naturally in the brain and is usually broken down before it reaches high levels but behaves differently in Alzheimer’s and PSP. Modified forms of tau protein form characteristic ‘tangles’ that are seen in both PSP and Alzheimer’s patients, leading to suggestions that drugs which block that clumping may have a therapeutic benefit.
Of course, a similar hypothesis has been put forward for drugs that interrupt the formation of amyloid plaques – the other characteristic feature of Alzheimer’s – and the development pathway is littered with failed amyloid-busting drugs.
Most recently, Eli Lilly revealed in November that its solanezumab candidate was unable to significantly slow cognitive decline in people with mild disease, although some glimmers of hope were seen in secondary outcome measures and candidates from the likes of Biogen and Roche remain in development.
Whether tau-targeting drugs can do better remains to be seen. Last year, TauRx’s tau aggregation inhibitor LMTX failed to slow cognitive decline in three phase III trials – two in Alzheimer’s and another in frontotemporal dementia (FTD). It was able to show other clinical effects, including a reduction in brain shrinkage.
TauRx also said it had cognitive benefit in a subset of patients not treated with existing treatments such as cholinesterase inhibitors, although this interpretation has been challenged and the company accused of overstating the results. Other tau-targeting failures in Alzheimer’s include Zeltia’s tideglusib, BMS’ epothilome D and Allon/Paladin Labs’ davunetide.
“We see potential in ABBV-8E12 and tau-focused approaches to progressive neurodegenerative diseases,” said Eric Karran, who heads AbbVie’s neuroscience R&D operations. The US FDA has awarded ABBV-8E12 fast-track designation for PSP, he said.
Other companies working on tau include Eisai/Biogen who are looking at combining a tau blocker with an anti-amyloid drug, as well as Bristol-Myers Squibb, AC Immune, Axon Neuroscience and Astellas.