Alzheimer’s sufferers see the advantages of Leqembi even when it’s stopped
Research at Biogen
New research from Eisai shows that Alzheimer’s patients taking Leqembi retain the benefits of the treatment even after they stop taking it.
The Japanese drugmaker and its partner Biogen last week released an additional analysis of clinical trials of the monoclonal antibody drug, also known as lecanemab. Alzheimer’s disease progressed more slowly in patients taking Leqembi, even after they had stopped treatment for an average of two years, the analysis found.
The results come as drugmakers await a decision on full approval of Leqembi. The Food and Drug Administration accelerated approval of the treatment in January and is scheduled to make its final decision on July 6. The findings also come as Eisai and Biogen try to regain a foothold after last year’s polarizing approval and disastrous launch of its other therapy for Alzheimer’s disease, Aduhelm.
About 6.7 million Americans age 65 and older are living with Alzheimer’s, according to the Alzheimer’s Association. This group is projected to grow to nearly 13 million by 2050.
One in three seniors will die of Alzheimer’s or another form of dementia, which kills more people than breast cancer and prostate cancer combined, the association said. The neurodegenerative disease begins with mild memory loss but eventually affects a person’s ability to think and perform day-to-day activities.
There is a wealth of research on Alzheimer’s, but treating it is notoriously difficult. Several drugs targeting the disease have failed in trials. The sheer cost and length of this research further hampers drug development. And in recent years, scientists have sparked a debate about the true cause of the disease and the goal of the drugs.
In the analysis, Alzheimer’s patients stopped taking Leqembi after 18 months in a phase II clinical trial and later resumed treatment in an extension study. Patients stopped Leqembi for a gap period of nine to 59 months before restarting it.
The analysis compared these patients to a group receiving a placebo.
Leqembi reduced amyloid plaques in patients at 12 and 18 months during the clinical trial, the analysis said. Amyloid is a protein that accumulates in the brains of Alzheimer’s patients and disrupts cell function.
The analysis said the reduction in amyloid plaques was accompanied by a “consequent reduction in clinical regression” compared to patients receiving the placebo. This means that Alzheimer’s disease progressed more slowly in patients who received Leqembi than in those who took placebo during the clinical trial.
According to the analysis, the difference in disease progression rate between the Leqembi and placebo groups remained the same throughout the gap between treatments. In other words, the disease progressed more slowly in patients taking Leqembi than in the placebo group, even during the time they were not taking the drug.
“The benefit that was obtained from the treatment continued,” said Dr. David Russell, director of clinical research at the Institute for Neurodegenerative Diseases, told CNBC.
“The disease has been put on hold for a period of time,” he added. “People have another year before they reach a more moderate stage of the disease compared to people who have not received treatment.”
The research institute is involved in clinical trials for Leqembi and other investigational Alzheimer’s drugs, including Eli Lilly’s donanemab and Genentech and AC Immune’s semorinemab.
Patients taking Leqembi also maintained low amyloid plaque levels during the gap period, the analysis found. The protein replenished only slightly after patients stopped taking the drug, with an average increase of about six centiloids. A centiloid is a unit used to measure amyloid in the brain.
This aligns with previous research from the National Institutes of Health showing that amyloid gradually builds up in the brain.
“It takes many decades for enough plaque to build up to damage the brain,” Russell said.
Other biomarkers of Alzheimer’s disease are still deteriorating
Alzheimer’s drug Leqembi can be seen in this undated handout picture obtained by Reuters on January 20, 2023.
Eisai | via Reuters
However, Russell emphasized that lower amyloid plaque levels in people taking Leqembi does not mean that the disease has stopped progressing. Leqembi and other Alzheimer’s drugs have shown an ability to slow cognitive decline, not stop the disease entirely.
“You don’t have to bring the plaque back to the level you had before treatment to start disease progression,” Russell said.
dr Lynn Kramer, Eisai’s chief clinical officer for Alzheimer’s and brain health, added that “plaque is just one component of the whole story and disease process.”
Blood tests in the analysis showed that other biomarkers of Alzheimer’s disease worsened when treatment was stopped, Kramer noted. For example, another protein called p-tau181 accumulated in the brain, a trend linked to cognitive decline.
“These biomarkers are indicative of ongoing brain injury and dysfunction,” Kramer said.
“Our data show that if you stop therapy after plaque removal, everyone will experience cognitive decline and biomarker disruption [monoclonal antibody] unless therapy continues,” he added.
Specifically, the analysis found that these disease biomarkers improved after patients resumed Leqembi during the extension study. Amyloid plaque also began to decrease just three months after restarting the drug.
These improvements were associated with a “greater slowdown” in cognitive decline after restarting treatment, the analysis said.