Arrowhead Pharmaceuticals said its experimental RNA interference drug, ARO-MAPT, crossed the blood-brain barrier and reduced tau protein in healthy volunteers. The highest dose, given as two subcutaneous injections two weeks apart, cut tau by an average of 73% after 105 days, with individual reductions as high as 85%. Arrowhead described the results as clinical validation of its platform for delivering RNAi drugs to tissues outside the liver.
The early-stage trial enrolled about 64 healthy volunteers across three dosing schedules. Low-dose subjects saw a 40% tau reduction at day 105; mid-dose subjects saw 69%. Reported side effects were mild and included injection-site reactions, bruising, respiratory infections and headaches. Stifel analyst James Condulis called the results compelling, but cautioned the drug remains at a very early stage and tau has yet to be clearly validated as an Alzheimer's target.
Alzheimer's drugs approved in recent years target amyloid beta and have shown modest benefits; tau accumulation is also believed to contribute to disease progression. Arrowhead plans to continue the trial with healthy volunteers and people with mild Alzheimer's disease, and to study ARO-MAPT in other tau-related conditions such as frontotemporal dementia and progressive supranuclear palsy.