Key Highlights

  • Roche's Preventron trial is testing trontinemab in 1,600 symptom-free people aged 55 to 80 at higher risk.
  • Lecanemab slowed decline by 27% over 18 months, and donanemab by 22% to 35% depending on the group studied.
  • An early trial cleared amyloid plaque in about 90% of patients within 28 weeks at higher doses.
  • A 2026 report counts 158 drugs in 192 trials, with amyloid targets falling from 33% to 20% of the pipeline.

A Push From Treatment to Prevention

Dementia affects tens of millions of people worldwide, and Alzheimer's disease is its most common cause. Despite decades of research there is no cure. New drugs have modestly slowed progression but have not halted or reversed it.

Swiss drugmaker Roche has now joined companies including Eli Lilly in pushing toward a new frontier, testing whether treatment can do more than slow cognitive decline and prevent symptoms from emerging in the first place.

How Trontinemab Tries to Reach the Brain

Trontinemab is an intravenous antibody designed to clear the amyloid plaques that accumulate in the brains of people with Alzheimer's. It aims to overcome a basic problem with the current generation of amyloid drugs, which is getting enough of the molecule into the brain.

Roche built the drug on its Brainshuttle platform, in which a side chain binds receptors on the blood-brain barrier, the protective layer of cells that keeps harmful substances out of the central nervous system, and helps the antibody cross. Roche estimates that this improves penetration into the central nervous system by 50 times or more. In an early-stage trial, the antibody cleared amyloid plaque in about 90% of participants within 28 weeks at higher doses, with low rates of brain swelling or bleeding. Roche is also running two Phase 3 trials, TRONTIER 1 and TRONTIER 2, in people with early symptomatic Alzheimer's.

What Existing Drugs Have Shown

Two amyloid antibodies are on the market. Lecanemab, from Eisai and Biogen, was approved in the United States in 2023 and in the UK in 2024, and it slowed decline by 27% over 18 months against a placebo. Eli Lilly's donanemab slowed decline over 18 months by 35% on one cognitive and functional measure in people with low or medium levels of tau protein, and by 22% across all participants. On a second measure the figures were 36% and 29%. Both drugs remove substantial plaque but slow cognitive decline only modestly.

They also carry risks, including brain swelling and bleeding, and are costly and complex to administer. Donanemab had a US list price of about USD 32,000 for a year of treatment at launch, before scans and aftercare. In the UK, the cost-effectiveness regulator NICE rejected both drugs in June 2025 after concluding that the clinical benefits were too modest to justify the cost to the health service. Appeal panels upheld several of the manufacturers' objections, and in March both appraisals were sent back to the NICE committee for reconsideration.

A Crowded and Widening Field

The modest effect underlines how little is understood about Alzheimer's. Scientists have identified the build-up of two proteins, amyloid and tau, as important, but genetics and other factors also play a part. Some patients still suffer after plaques are cleared, and some people with plaques never develop the condition.

Researchers are therefore pursuing more targets. A report published in May counts 158 drugs in 192 clinical trials, up from 138 drugs in 182 trials a year earlier. Amyloid-targeting drugs make up about 20% of the pipeline, down from about 33% a decade ago, while drugs aimed at tau and at inflammation or immune dysfunction have each risen from about 6% to about 20%. Roche is one of a growing group working on ways to carry drugs into the brain, and this year Denali won the first US approval for a biologic designed to cross the blood-brain barrier, for Hunter syndrome.

Prevention and the Blood Test

In September, a UK site run by Surrey and Borders Partnership NHS Foundation Trust, the first in Europe, began offering trontinemab in Preventron, a Phase 3 trial of about 1,600 people worldwide aged 55 to 80 who have no symptoms but a high risk of developing the disease. Participants are screened with a blood test for the p-tau217 biomarker and a memory test. In a description of the design, participants receive either a placebo or trontinemab at 3.6 milligrams per kilogram, with monthly infusions for six months and quarterly infusions after that. The main measure is time to progression to a score above zero on a standard dementia rating scale.

The trial relies on a blood test for pTau217, a biomarker of amyloid pathology, which Roche developed in collaboration with Lilly and which received European CE certification, announced on May 12. The test is intended to help rule amyloid pathology in or out in people with memory complaints, and could reduce reliance on costly PET scans and invasive lumbar punctures.

What Has to Be Proven Before Prevention Counts

Prevention rests on two links that have not yet been shown to hold. The first is whether clearing amyloid changes symptoms enough to matter. The antibodies on the market remove plaque yet slow decline only modestly, and some people with plaques never develop the disease. The second is whether a blood test can reliably find the people who benefit before symptoms appear, at a cost health systems accept.

Other prevention trials set comparisons. Lilly is testing donanemab in people without symptoms in TRAILBLAZER-ALZ 3, and lecanemab is being tested in AHEAD 3-45, whose readout one research report places in 2028. NICE's reconsideration of lecanemab and donanemab shows how health systems weigh modest benefits against cost and complexity.