A monoclonal antibody treatment for Alzheimer’s disease that showed promise in a Phase 3 trial may have contributed to a study participant’s death, according to an adverse events report obtained by the digital health publication Stat.
Eisai, the company that makes the experimental drug lecanemab, said in a statement to CNN on Friday that because of patient privacy issues, it could not provide specific information about patients or comment on information from other sources.
Stat reported that an investigator on the study told Eisai about the death and that it was a result of bleeding in the brain. The investigator had concluded that the bleed was related to the drug, but the company pointed to other possible factors.
The company told Stat that there was “at least a reasonable possibility lecanemab may have contributed to the” hemorrhage. Other factors may have been the participant’s “multiple falls, a heart attack, a respiratory infection, and mini-stroke-like events,” according to Stat. The participant in question was also on blood thinners for a heart condition, according to the adverse events report Stat says it reviewed. Stat says the death is still being investigated.
“STAT News was accurate overall in how difficult it can be to determine the specific cause of death in any given patient, in particular when they are elderly and have multiple medical problem,” Eisai’s statement said.
The company said it has created a rigorous safety monitoring process to make sure participants are safe, including an independent data safety monitoring committee of outside experts, and said it promptly communicated safety information to investigators, regulators and participants.
The company added that in Phase 2 of the trial, the rate of deaths in participants who received the drug “was no more frequent” than in those who got a placebo.
“The well-being of the patients enrolled in our clinical studies is always Eisai’s top priority,” the statement says.
Dixie Ecklund, president-elect of the Society for Clinical Trials, acknowledged that deaths can certainly happen in the course of testing a new drug but thinks trials remain crucial “because with scientific rigor, you can design trials well and get answers and then make a difference in our society.” Ecklund is not affiliated with Eisai and was not involved in the trials.
She points to the importance of an outside data safety monitoring board with this trial, as these boards are “very particular about scientific rigor.”
“There are lots of checks and balances built into clinical trial industry in the United States between the FDA and NIH, peer review, and all those things can lead to the ability for an individual to make a responsible assessment.”
In September, Eisai reported preliminary results from the trial that found the treatment slowed the progression of cognitive decline by 27% compared with a placebo.
It also met all secondary endpoints, showing “target engagement” with reduced amyloid levels – a protein that is one of the hallmarks of Alzheimer’s – and positive effects on cognition and the ability to perform everyday tasks when compared with a placebo.
The company said at the time that it believed that the study results “prove the amyloid hypothesis, in which the abnormal accumulation of [amyloid beta] in the brain is one of the main causes of Alzheimer’s disease.”
Dr. Richard Isaacson told CNN in September that this is not proof per se but that the trial was signficant. Isaacson is the director of the Alzheimer’s Prevention Clinic in the Center for Brain Health at Florida Atlantic University’s Schmidt College of Medicine.
“In the past, reducing amyloid in the brain has not always been tied to cognitive improvements or any meaningful clinical improvements. In this study, every endpoint was positive. That’s never happened before.”
The early results showed that nearly 3% of the trial participants who took the drug had a side effect called ARIA-E, swelling in the brain, but no one who took the placebo did.
The rate of symptomatic ARIA-H, brain bleeding and iron buildup in tissue, was 0.7% in the drug group and 0.2% in the placebo group.
Eisai will present the results from the drug trials at the Clinical Trials on Alzheimer’s Disease conference in late November.
Eisai, which is working with the company Biogen, said they plan to publish the results in a peer-reviewed journal and seek approval from US regulatory authorities by the end of March.