Alzheimer’s patients who take Leqembi retain the benefits of the treatment even when they stop taking it, new research by Eisai shows.
The Japanese drugmaker and its partner Biogen last week released an additional analysis of clinical trials of the monoclonal antibody drug, which is also known as lecanemab. Alzheimer’s disease continued to progress at a slower rate in patients who took Leqembi even when they were off the treatment for an average of two years, the analysis found.
The findings come as the drugmakers await a decision on full approval of Leqembi. The Food and Drug Administration approved the treatment on an expedited basis in January, and is slated to make its final decision on July 6. The findings also come as Eisai and Biogen try to regain their footing after the polarizing approval and disastrous rollout last year of its other Alzheimer’s disease therapy, aduhelm.
Roughly 6.7 million Americans age 65 and older are living with Alzheimer’s, according to the Alzheimer’s Association. That group is projected to rise to almost 13 million by 2050.
One in three seniors die with 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 impairs a person’s ability to think and carry out daily activities.
There is a wealth of research on Alzheimer’s, but it has been notoriously difficult to treat. Multiple drugs designed to target the disease have failed in trials. The sheer cost and length of that research further impede drug development. And in recent years, scientists have ignited a debate over the true cause of the disease and what the drugs should target.
In the analysis, Alzheimer’s patients stopped taking Leqembi after 18 months in a phase two clinical trial and later resumed the treatment in an extension trial. Patients stopped Leqembi for a “gap period” that ranged from nine to 59 months before restarting it.
The analysis compared those patients to a group that received a placebo.
Leqembi reduced amyloid plaque in patients after 12 and 18 months during the clinical trial, the analysis said. Amyloid is a protein that builds up on the brain in Alzheimer’s patients and disrupts cell function.
The analysis said amyloid plaque reduction was accompanied by a “consistent reduction of clinical decline” compared to patients who received the placebo. That means Alzheimer’s disease progressed at a slower rate in patients who received Leqembi compared to those who took the placebo during the clinical trial.
The difference in disease progression rates between the Leqembi and placebo groups stayed the same during the gap period between treatments, according to the analysis. In other words, the disease continued to progress more slowly in patients who took Leqembi compared to the placebo group even during the period they were not taking the drug.
“The benefit that had been derived from being on treatment persisted,” Dr. David Russell, director of clinical research for the Institute for Neurodegenerative Disorders, told CNBC.
“The disease was set back for a certain amount of time,” he added. “People get another year before they progress to a more moderate stage of disease compared to the people who didn’t get any treatment.”
The research institute is involved with clinical trials for Leqembi and other experimental Alzheimer’s drugs, including Eli Lilly‘s donanemab and Genentech and AC Immune’s semorinemab.
Patients who took Leqembi also retained low levels of amyloid plaque during the gap period, the analysis noted. The protein only reaccumulated slightly after patients stopped taking the drug, with an average increase of about six centiloids. A centiloid is a unit to measure amyloid in the brain.
That’s consistent with prior National Institutes of Health research that shows amyloid gradually builds up in the brain.
“It takes many decades to build up enough plaque to start getting damage to the brain,” Russell said.
Other biomarkers of Alzheimer’s disease still worsen
But Russell emphasized that lower levels of amyloid plaque seen in people taking Leqembi don’t mean the disease stops progressing. Leqembi and other Alzheimer’s drugs have demonstrated the ability to slow cognitive decline, not stop the disease entirely.
“You don’t have to get the plaque back up to the level that it was before taking the treatment to start getting disease progression,” Russell said.
Dr. Lynn Kramer, Eisai’s chief clinical officer of Alzheimer’s disease and brain health, added that “plaque is only a component of the whole story and the disease process.”
Blood tests in the analysis showed that other biomarkers of Alzheimer’s disease worsened when treatment stopped, Kramer noted. For example, another protein called p-tau181 accumulated in the brain, a trend associated with cognitive decline.
“These biomarkers are signs of continuing brain injury and dysfunction,” Kramer said.
“Our data illustrates that when you stop therapy after removing plaque, cognitive decline and biomarker disruptions are going to happen with any [monoclonal antibody] unless therapy is continued,” he added.
Notably, the analysis said those disease biomarkers improved once patients restarted Leqembi during the extension trial. Amyloid plaque also began to decrease after as little as three months after patients resumed the drug.
Those improvements were associated with a “greater slowing” of cognitive decline after treatment restarted, according to the analysis.