Major trial of Roche Alzheimer's drug kicks off in Europe

An NHS trust in the UK has become the first site in Europe to offer Roche's experimental drug trontinemab to patients enrolled in a large-scale trial to see if it can delay or prevent Alzheimer's disease.

The phase 3 PrevenTRON study – which gets underway in World Alzheimer’s Month – will recruit around 1,600 people aged 55 to 80 around the world who have no symptoms of Alzheimer’s or memory problems, but who are at high risk of developing the disease.

Participants will be screened for memory loss and given a blood test to check for the p-tau217 biomarker before receiving trontinemab, an intravenously administered anti-amyloid antibody that is designed to transfer into the central nervous system more effectively than current amyloid-directed therapies.

The drug is thought to clear the amyloid plaques in the brain that characterise Alzheimer's more quickly than Eisai/Biogen's Leqembi (lecanemab) and Eli Lilly's Kisunla (donanemab) – the only two anti-amyloid currently approved for marketing – eradicating them in weeks or months, instead of taking a year or more.

PrevenTRON also differs from most earlier Alzheimer's prevention studies because it is recruiting at-risk subjects who are cognitively healthy, rather than those displaying the first signs of mild cognitive impairment or mild dementia.

"For decades, research has focused on treating Alzheimer’s disease after symptoms appear," commented PrevenTRON's chief investigator, Prof Ramin Nilforooshan, a psychiatry consultant at the University of Surrey.

"PrevenTRON addresses a different question: whether we can act earlier, before symptoms begin," he added. "Through research and trials like PrevenTRON, we are very excited for the potential to help millions of people affected by Alzheimer’s disease."

The trial is now underway in the UK at Surrey and Borders Partnership NHS Foundation Trust, which is the lead recruitment site in the UK and can recruit subjects from anywhere in the country.

PrevenTRON is one of a trio of phase 3 trials Roche is running of trontinemab, alongside two studies in early symptomatic Alzheimer's (TRONTIER 1 and 2).

The drug has emerged from the Swiss group's Brainshuttle antibody engineering platform, which adds a "side chain" to antibodies that binds to receptors on the blood-brain barrier – designed to protect the brain from toxins and pathogens – and makes it easier to penetrate the CNS.

It is estimated that less than 1% of some anti-amyloid antibodies reach the CNS, where they can exert their activity, but Roche estimates that trontinemab can improve that by 50 times or more.

In the phase 1b/2a Brainshuttle AD trial, the antibody cleared amyloid plaques in around 90% of subjects within 28 weeks at higher dose levels, with a very low incidence of brain swelling or bleeding side effects that have been linked to current drugs.