Roche reveals patient death in Alzheimer’s study

An elderly patient died in a clinical trial for Roche’s experimental Alzheimer’s disease treatment, prompting changes to the study design, although the company said the overall results supported further research.

The data release was part of a data presentation Wednesday at an Alzheimer’s disease clinical trials conference in which Roche said its drug showed the ability to rapidly remove toxic proteins while avoiding side effects commonly associated with existing treatments.

“Overall, I think the data is reassuring,” Luka Kulic, program manager for the drug, said in an interview before the presentation. According to the latest data, Roche collected information on 160 patients receiving four different doses of the drug or a placebo. According to Kulic, those receiving the highest dose saw “rapid and robust” removal of amyloid, protein aggregates often seen as a hallmark of Alzheimer’s disease.

Roche shares fell slightly on Wednesday. Since the beginning of the year, the company’s shares have increased by over 12 percent.

Roche wants to make progress in a market that analysts say could be multibillion. While it is too early to tell whether the drug trontinemab can slow cognitive decline, Roche said it also has an impact on “downstream biomarkers” that can predict brain function.

Perhaps more exciting, Kulic added, is the low rate of amyloid-related imaging abnormalities, or ARIA – swelling or bleeding in the brain seen on magnetic resonance imaging. Across all dose groups, ARIA rates ranged from 3 to 7 percent.

Similar treatments, including Eli Lilly & Co’s Kisunla and Biogen and Eisai’s Leqembi, have shown much higher ARIA rates, ranging from 21 to 36 percent, according to FDA labeling, with the caveat that these numbers have been seen in much larger clinical trials about different schemes. The modified dosing regimen may lower the incidence of ARIA, Lilly reported at the same conference on Tuesday.

Roche said the patient who died in the trial was a 78-year-old woman. She did not develop ARIA, but did experience bleeding in the right frontal lobe after receiving the second dose. A spokesman confirmed that Roche voluntarily paused registration for several weeks to investigate the matter and make adjustments to the study protocol.

Roche added that the investigation found several risk factors that may have contributed to the death, including lesions suggesting previous bleeding in the brain. As a result, the company changed its registration criteria to exclude people suffering from the same disease, called superficial siderosis.

“We obviously only have one case and it is always difficult to draw final conclusions based on one case,” Kulic said. “But that’s just our assessment that we wanted to share with the community.”

Having completed the first part of the Phase 1 study, Roche is now moving on to the second phase, testing the two highest doses in a larger number of patients. The study also plans to examine different dosing regimens, including higher doses than currently studied, and the long-term effects of trontinemab.

Trontinemab is a newer version of gantenerumab, Roche’s previous big Alzheimer’s drug, which ultimately failed to slow cognitive decline in late-stage trials. Both drugs aim to remove amyloid, as do the recently approved drugs Kisunla and Leqembi.

Roche CEO Thomas Schinecker recently expressed optimism about trontinemab, which uses brain shuttle technology to cross the protective blood-brain barrier.