Roche Discloses Patient Death in Alzheimer’s Trial

(Bloomberg) — An elderly patient died in a clinical study of Roche Holding AG’s experimental treatment for Alzheimer’s disease, prompting changes to the trial design, although the company said overall results support further testing.

The disclosure was part of a data presentation on Wednesday at a conference focused on Alzheimer’s clinical trials, where Roche said its drug showed the ability to quickly wipe out a toxic protein while avoiding side effects commonly associated with existing therapies.

“Overall I think the data are reassuring,” said Luka Kulic, program lead for the drug, in an interview ahead of the presentation. At the latest data cut, Roche has collected information on 160 patients receiving four different doses of the drug or placebo. Those receiving the highest dose saw “rapid and robust” clearance of amyloid, the protein aggregates often viewed as the hallmark of Alzheimer’s disease, according to Kulic. 

Roche shares fell slight in early trading Wednesday. The stock is up more than 12% since the start of the year.

Roche is looking to make headway in what analysts predict could be a multibillion-dollar market. While it’s too early to tell whether the drug, trontinemab, could slow cognitive decline, Roche said it also had an effect on “downstream biomarkers” that could be predictive of brain function.

Safety Profile

Perhaps more exciting, Kulic added, is the low rate of amyloid-related imaging abnormalities, or ARIA — brain swelling or bleeding observed on magnetic resonance imaging. Across all dose groups, ARIA rates were between 3% and 7%. 

Similar treatments, including Eli Lilly & Co’s Kisunla and Biogen Inc. and Eisai Co’s Leqembi, have reported much higher ARIA rates between 21% and 36%, according to their FDA labels, with the caveat that those figures were observed in much larger clinical trials with different designs. A modified dosing schedule could lower ARIA rates, Lilly reported at the same conference on Tuesday. 

What Bloomberg Intelligence Says:

Roche’s brain shuttle trontinemab could raise the bar in Alzheimer’s with its rapid and deep amyloid clearance of 67-75% at 28 weeks vs. 37.9% with Lilly’s Kisunla. The brain inflammation rate (ARIA-H) at 28 weeks was 5.7%, substantially lower than the 31% seen with Kisunla. If replicated in a larger, and longer study, Trontinemab may outcompete Leqembi and Kisunla, each expected to reach sales of $3.5 billion in 2030.

— Sam Fazeli, BI pharma analyst

Roche Alzheimer Drug Beats Biogen Leqembi, Lilly Kisunla: React

The patient who died in the trial was a 78-year-old woman, Roche said. She did not develop ARIA but experienced bleeding in the right frontal lobe after receiving the second dose. Roche voluntarily paused enrollment for weeks to investigate the case and implement amendments to the trial protocol, a spokesperson confirmed.

The investigation found several risk factors that could have contributed to the death, Roche said, including lesions that suggested a previous bleed in the brain. As a result, the company changed the enrollment criteria to exclude anyone with the same condition, known as superficial siderosis.

“We have, of course, only one case, and it’s always difficult to make definitive conclusions on this based on one single case,” Kulic said. “But this is simply our assessment that we wanted to share with the community.”

Both Kisunla and Leqembi’s labels carry warnings about potential serious intracerebral hemorrhages. The exclusion of patients with superficial siderosis is in line with recently published recommendations for the use of anti-amyloid therapies, according to Bloomberg Intelligence analyst Jean Rivera Irizarry.

Trial Design 

Having completed the first part of the Phase 1 study, Roche is now moving ahead with the second stage, testing the two highest doses in more patients. It also plans to examine different dosing regimens, including higher doses than currently tested, and long-term effects of trontinemab as part of the trial. 

Trontinemab is a newer version of gantenerumab, Roche’s previous big bet on Alzheimer’s that ultimately failed to slow cognitive decline in late-stage trials. Both drugs are designed to clear amyloid, just like recently approved Kisunla and Leqembi treatments. 

Roche Chief Executive Officer Thomas Schinecker recently expressed optimism for trontinemab, which deploys a brain shuttle technology to slip past the protective blood-brain barrier.

(Updates with Lilly study in seventh paragraph. A previous version corrected dosing information in third paragraph.)

©2024 Bloomberg L.P.