With phase 2 trials now underway, AbbVie says it intends to drive its anti-tau antibody for neurodegenerative disorders such as Alzheimer's "as quickly as possible."
The company announced the start of its midstage trial program for ABBV-8E12 last week, with one study in Alzheimer's patients and another in the rare neurodegenerative condition progressive supranuclear palsy (PSP).
The trial protocols give a timeline for primary results readout for Alzheimer's in 2020 and for PSP 2019, respectively, but AbbVie's chief scientific officer Michael Severino says they have been designed with "a number of opportunities" to get data in the interim.
Just when those opportunities may arise isn't yet clear, but it is apparent that AbbVie has high hopes for the tau-busting approach at a time when the majority of its peers in the biopharma sector are still focused on developing drugs that target amyloid beta, despite repeated failures in clinical trials. Most recently, Eli Lilly was forced to give up on amyloid-busting drug solanezumab after a failed trial in mild Alzheimer's patients.
Like amyloid, tau forms one of the trademark structural changes that can be seen in the Alzheimer's brain. While Amyloid forms plaques, tau forms neurofibrillary tangles in the brains of patients with Alzheimer's and PSP and—according to Severino— there are differences in the pattern of the pathology between the amyloid and tau which suggest the latter could be a better target.
Amyloid beta pathology peaks very early and is essentially stable at the time that disease progression occurs and it doesn't correlate particularly well with the area of the brain where neurons degenerate, he said on the firm's fourth-quarter conference call.
On the other hand, tau "tracks much more closely with both neuronal dysfunction and clinical symptoms"—both in terms of time and the area of the brain affected by the disease, he told investors. AbbVie's antibody is designed to block the spread of tangle formation through the brain.
"We think that the [phase 2] data will indicate a strong role of time for tau and a strong role for our mechanism," said Severino, who was instrumental in broadening AbbVie's R&D focus to include neuroscience after he took the CSO role in 2014. "Ultimately of course the phase 2 study and downstream studies will answer those questions definitively."
Fewer biopharma companies have opted to follow the tau route, and among those that have done so there have also been trial failures. The leading proponent of the tau hypothesis—TauRx—suffered a blow last year when its LMTX candidate failed to slow cognitive decline in Alzheimer's and another neurodegenerative condition called frontotemporal dementia (FTD).
The company was criticised for over-playing the importance of some secondary findings such as a reduction in brain atrophy that it said could suggest a positive benefit for the drug. Nevertheless, it is pressing on with the drug's development, while other drugmakers including Eisai/Biogen, Bristol-Myers Squibb and Astellas have also indicated they have tau programs in the pipeline.
AbbVie in-licensed ABBV-8E12 from C2N Diagnostics in March 2015.