Arrowhead Pharmaceuticals reported interim Phase 1/2a results for ARO-MAPT, an RNA interference therapy aimed at Alzheimer’s disease and other tauopathies, showing deep reductions in cerebrospinal fluid total tau after a subcutaneous injection.
In healthy volunteers, mean CSF total tau fell by up to 73% at Day 105, with a maximum individual reduction of 85%. The company says the durability supports the potential for quarterly dosing.
First clinical proof for crossing the blood-brain barrier
The more consequential claim is delivery. Getting siRNA across the blood-brain barrier has long been the field’s central obstacle, and Arrowhead describes these results as the first clinical validation of its TRiM platform for doing exactly that after a simple subcutaneous shot.
Nobody has yet shown that lowering tau changes how patients fare. Tau is a reasonable target on the strength of genetics and pathology, but several tau-directed programs have faltered on clinical endpoints, so the biomarker win is a signal rather than an answer.
Arrowhead discussed additional interim data in a webinar featuring Adam Boxer of the University of California, San Francisco, a leading figure in tau research.
