A Tau-Targeting Drug Just Cleared Toxic Tangles From Alzheimer's Brains for the First Time

An experimental Alzheimer's drug has become the first to show that clearing toxic tau protein from the brain can be paired with a measurable slowing of mental decline, according to detailed mid-stage results presented at the Alzheimer's Association International Conference in London. The drug, Biogen's diranersen, targets tau — one of the two hallmark proteins that build up in the brains of people with the disease.

The results were genuinely mixed, and closely watched. In the Phase 2 CELIA study of 416 people with early Alzheimer's, diranersen did not meet its primary statistical goal, a setback that tempered enthusiasm and, in earlier topline disclosures, weighed on the company's stock. Yet across a battery of secondary measures, patients on the drug declined more slowly than those on placebo — by roughly 9 to 14 percent on one widely used dementia rating scale, and by larger margins on several other cognitive and functional tests.

Just as important to researchers, the drug delivered on the biology it was designed to change. Diranersen is an antisense oligonucleotide, a short strand of engineered genetic material that switches off production of tau before the protein is even made. Patients showed sustained reductions in tau in their cerebrospinal fluid and in tau pathology measured by brain scans across all doses tested — evidence that the therapy was hitting its target and reducing the tangles associated with the death of brain cells.

For decades, Alzheimer's drug development focused overwhelmingly on the other hallmark protein, amyloid, which forms sticky plaques between neurons. The first amyloid-clearing antibodies have reached the market but offer only modest benefits and carry risks of brain swelling and bleeding. Tau, which accumulates inside neurons and tracks more closely with the timing and severity of symptoms, has long been considered a promising but frustratingly elusive alternative target.

Safety data offered some reassurance. The most notable side effect, episodes of a confusional state, tended to appear within a few days of a dose and generally resolved within about a week. Biogen said the drug was otherwise consistent with the profile seen in its earlier trials.

Citing what it called a growing and consistent body of evidence from its Phase 1b and Phase 2 programs, Biogen said it plans to advance diranersen into a confirmatory Phase 3 trial — the final and most rigorous stage before any application for approval. Independent experts cautioned that a missed primary endpoint is a real warning sign, and that only a large Phase 3 study can establish whether the benefits are durable and meaningful to patients. Even so, many described the tau results as a milestone for a field badly in need of new directions.