In late November 2022, Eisai presented the full findings of its Phase 3 Clarity AD clinical trial for lecanemab at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
During the clinical trial, about 1,800 adults ages 50 to 90 with early Alzheimer’s disease received either lecanemab or a placebo. Participants also received assessments of certain cognitive and functional skills both before the trial began, and 18 months later.
Finally, the participants undertook PET scans to check for the presence of amyloid in the brain.
At the 18-month follow-up, researchers reported people who took lecanemab slowed their cognitive decline by 27% compared to those who took the placebo.
“Results of the Clarity clinical trial also demonstrated lecanemab had beneficial effects on biomarkers for amyloid, tauTrusted Source, and other pathophysiology measures,” Dr. MacSweeney said. “So lecanemab not only directly removed amyloid plaques but also had downstream effects on tau pathology.”
‘Clinically meaningful’ results
Upon hearing the presented data at the CTAD conference, Dr. Ronald Petersen, a neurologist and director of the Mayo Clinic Alzheimer’s Disease Research Center and the Mayo Clinic Study of Aging, told MNT the data were “pretty impressive.”
“The drug did what it was supposed to do — it engaged the appropriate target in the brain, namely amyloid, and removed a bunch of it such that most of the people got down to the actual threshold level for amyloid, meaning they removed it down to the negative threshold for having amyloid in the brain,” he explained.
“And then there was a corresponding clinical response to that as well,” Dr. Petersen added. “It was a modest clinical response — it didn’t stop the disease, it didn’t make anybody better, not that it was supposed to. And it did what it was supposed to. And I think the level of stabilization in the people who were treated with the drug is clinically meaningful.”
Lecanemab potential side effects
Upon the conclusion of the trial, researchers also reported some potential side effects from the use of lecanemab.
According to Dr. MacSweeney, lecanemab was generally well tolerated and the most common side effects were:
an infusion-related reaction, as the medication is delivered by intravenous infusionTrusted Source every 2 weeks
headaches.
ARIA, she explained, is a side effect that involves a bleed or build-up of fluid in the brain.
“The ARIA incidence profile was within expectations in the Clarity study and symptomatic ARIA was low,” Dr. MacSweeney said.
“So for those who did develop evidence of ARIA, this was mostly asymptomatic, meaning the patient was unaware they had developed the condition; it was detected only by MRI, and in most cases treatment continued and did not result in the study not reaching its conclusion and will not influence application to [the] FDA and regulatory bodies in other countries for a license for lecanemab to be available in the market,” she noted.
MNT also spoke with Dr. Verna Porter, a neurologist and director of the Dementia, Alzheimer’s Disease and Neurocognitive Disorders at Providence Saint John’s Health Center in Santa Monica, CA, who stated that although ARIA can sometimes be lethal, it is treatable if the medication that causes it is stopped or the dose reduced.
“In the approval process, the FDA will need to consider data from the trial showing that people taking anticoagulant drugs may have a slightly higher risk of bleeding events, before determining whether lecanemab requires an additional warning label about potential hemorrhage risk,” she said. “The FDA will also need to review and compare the risk of ARIA-E among people taking lecanemab with the risk associated with other amyloid-lowering drugs.”
Second death linked to lecanemab
On November 27, 2022, Science published an article reporting of a second death linked to lecanemab. A 65-year-old woman who reportedly received infusions of lecanemab during the clinical trial experienced a stroke and ultimately died from a brain hemorrhage.
When asked about this development, Dr. Petersen explained that while lecanemab removes amyloid from the brain, it also removes it from blood vessels in the brain.
“People with Alzheimer’s disease also have this amyloid protein in the blood vessels, so when they remove some of the amyloid from the blood vessels, it can make them leaky,” he detailed. “And that means that there can be swelling in the brain and there can be bleeding in the brain.”
“That needs to be told to the patients and the patients, families, and doctors will have to make a collective decision about the risks versus the benefits,” Dr. Petersen continued.
“The risks are real,” he stressed, “but I think they’re relatively low and they generally can be monitored by serial imaging with MRI scans to make sure this doesn’t take off. But there’s always the unexpected risk of somebody having a major bleed in the brain.”
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