Following up on its October surprise, Biogen showed more data at the Clinical Trials in Alzheimer’s Disease conference, arguing that disparities in drug exposure explained the puzzlingly different outcomes in its one positive and one negative aborted Phase 3 trials. Audience members were put off by the messiness of the data set and not fully convinced by the analysis, but the majority said they believed the general signal that the antibody may slow disease progression. The prevailing mood was one of hopefulness, with most agreeing the results validate the amyloid hypothesis and suggest that effective treatments for AD are within reach.
Biogen researchers claim the antibody worked in people who got enough of it. To other researchers, the signal validates the amyloid hypothesis and injects fresh energy into the field. But is this interrupted dataset enough to approve?
An expanded set of CSF biomarkers exposed tight connections between p-tau, synaptic dysfunction, and neuroinflammation in people with brain amyloid.
Using mass spectrometry to detect teensy amounts of phospho-tau species in plasma, researchers reported that p-tau-217 and p-tau-181 picked out people with Aβ pathology. Differences between groups appear to be huge. An MS-based test for plasma Aβ42 corresponded to brain amyloid, and is going in for regulatory approval.
Plaque-busting antibodies reset the time course of amyloid accumulation, but so far provide only hints of a clinical benefit in mild AD. Good news: once gone, plaque stays gone for a while.
At CTAD, researchers discussed possible paths forward. One option: exploring whether low doses prevent plaque accumulation while avoiding the cognitive side effects.
Apabetalone, an epigenetic drug that tamps down vascular inflammation, slowed cognitive decline in people with MCI. A new statistical analysis of results from AMBAR claimed the plasma-exchange therapy might boost cognition by removing pathogenic proteins from blood.
A half-dozen lesser-known compounds in trials for Alzheimer’s disease posted results at the CTAD conference.
Data from different next-generation tracers look similar. It shows spreading plaques kick off tangles by Braak region; memory starts slipping later.
Besides further broadening the Alzheimer’s therapeutic pipeline, researchers urge a return to Phase 2, using artificial intelligence tools to streamline aspects of trials.