Pharma says new Phase 3 trial of trontinemab will have the goal of ‘delaying or preventing progression of the disease to symptomatic stages.’
At this week’s ongoing Alzheimer’s Association International Conference (AAIC), pharma giant Roche made a flurry of announcements spanning its diagnostics and drug development portfolios, with one in particular catching the eye. The company revealed it is planning a Phase 3 clinical trial of its investigational drug trontinemab in individuals “at risk” of developing Alzheimer’s, meaning those who are not yet experiencing cognitive decline but are categorized as being in the preclinical phase of the disease.
In Alzheimer’s, irreversible neuronal damage often precedes noticeable memory loss by many years. It is hoped that earlier intervention could help delay or even prevent the cascade of brain pathology that leads to clinical dementia.
Roche was already planning Phase 3 studies of trontinemab in patients with early symptomatic Alzheimer’s disease later this year, but the primary aim of the new trial is to determine whether trontinemab can delay or even prevent the progression from preclinical signs to symptomatic stages of Alzheimer’s. This is significant because it represents a shift from focusing on treating symptomatic patients to implementing potentially preventive strategies at earlier stages.
“Alzheimer’s disease represents one of the greatest challenges in healthcare today and tackling it requires early detection and effective therapeutics,” said Roche’s Chief Medical Officer Dr Levi Garraway. “Trontinemab is designed to target a key driver of Alzheimer’s disease biology more effectively in the brain. Combining new treatment avenues with advanced diagnostics may enable earlier and potentially more effective intervention. With plans for Phase III trials in both early symptomatic and preclinical Alzheimer’s disease, we are advancing science with the goal of delaying – and ultimately preventing – progression of this devastating condition.”
Trontinemab is an investigational monoclonal antibody developed using Roche’s “Brainshuttle” technology. It has a bispecific format, which means it can both bind to aggregated amyloid-beta plaques (a key hallmark of Alzheimer’s disease) and efficiently cross the blood-brain barrier by targeting transferrin receptors (TfR1) on brain endothelial cells. According to Roche, the drug’s design allows for much higher antibody concentrations in the brain than conventional monoclonal antibodies, potentially enabling rapid removal of amyloid plaques at lower doses and with fewer side effects.
The company also reported promising results from its ongoing Phase 1b/2a Brainshuttle AD study, which demonstrated that trontinemab can achieve fast and significant reduction of amyloid plaques. In high-dose cohorts, 91% of participants became amyloid PET-negative after 28 weeks of treatment. The drug’s safety profile also appears to be favorable, with serious brain swelling seen in fewer than 5% of treated patients and all such cases described as mild.
If trontinemab’s promise is borne out in the new trial, it could catalyze a paradigm shift in Alzheimer’s care – moving from reactive to proactive intervention, and potentially offering the prospect of delaying or preventing the onset of cognitive impairment.
