Roche reveals early results for new amyloid-based Alzheimer's treatment

On Wednesday, Roche shared initial data from its new Alzheimer’s program, aiming to re-enter a challenging field haunted by numerous failures. This early-stage study involved 60 patients who were administered four different doses of trontinemab. According to Roche’s researchers, the antibody significantly reduced amyloid plaque at a “rapid and robust” pace, while inducing relatively low rates of brain swelling and bleeding, known as ARIA. However, there was a patient fatality due to a significant brain bleed resembling a stroke, which was not categorized as ARIA.

The future direction of the program remains uncertain, as Roche still needs to finalize the ongoing trial and its open-label extension, stated Luka Kulic, the head of the trontinemab program. Furthermore, the trial did not evaluate the drug’s impact on patient cognition, an aspect that regulators would likely focus on in a pivotal trial.

Nonetheless, these findings represent a crucial initial step for Roche in its renewed efforts to tackle Alzheimer’s, following several unsuccessful Phase 3 trials of gantenerumab, another anti-amyloid antibody licensed from MorphoSys, in 2015 and 2022. The negative results essentially caused Roche to lose ground to other amyloid-targeting Alzheimer’s drugs, such as Eisai and Biogen’s Leqembi and Eli Lilly’s Kisunla, both of which have received FDA approval.

In the latest trontinemab study, patients who received the highest dose exhibited a 67% reduction in amyloid levels after 28 weeks when compared to the placebo group, and a 75% reduction in the second-highest dose group. These patients were also classified as “amyloid negative” based on PET scan results. Only one patient in the second-highest dose group experienced an ARIA-related event.

Kulic explained that these results represent the latest development in the amyloid hypothesis — a long-standing theory that eliminating amyloid plaques in the brain can alleviate the cognitive impairments characteristic of Alzheimer’s disease. Historically, pharmaceutical companies have struggled to create therapies that improve cognition, despite the approval of Leqembi and Kisunla, which still carry significant risks.

Kulic is optimistic that these preliminary results will lead to more promising data in larger clinical trials. “We believe that we are really well on track, because trontinemab gets the [amyloid] levels below the [amyloid negativity] threshold faster than probably any other molecule that is currently out there,” he said.

Trontinemab is uniquely designed with what Roche calls a “Brainshuttle” module attached to the antibody, enhancing its ability to cross the blood-brain barrier. Last year, Roche reported that amyloid levels dropped below normal detection thresholds in 75% of patients after 28 weeks at the highest dose tested.