The new FDA-approved Alzheimer's treatment Leqembi is being prepared at Abington Neurological Associates in Abington, PA, on Tuesday, November 7, 2023.
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New data released by Japanese drugmaker Eisai on Tuesday showed that its leading Alzheimer's drug Leqembi slowed the progression of the disease in patients over three years, highlighting the need for them to continue taking the treatment long-term.
Results of the study on Leqembi, which Eisai shares with BiogenThe study also found that the patient’s Alzheimer’s disease worsened after stopping treatment. Rates of adverse side effects associated with Leqembi, including brain bleeding and swelling, decreased after six months of treatment, Dr. Lynn Kramer, Eisai’s chief clinical learning officer for human biology, told CNBC.
This is a significant decline: These side effects in the brain have raised concerns among some doctors, and are the main reason why the European Medicines Agency recommended against approval of Lekmebi last week.
The study is the longest available to date on the efficacy and safety of Leqembi, which has faced a rocky rollout in the United States since it won regulatory approval last summer due to bottlenecks related to diagnostic testing requirements and regular brain scans, among other issues. Eisai released 24-month data on Leqembi in November.
Eisai presented the results Tuesday at the Alzheimer’s Association International Conference in Philadelphia, the world’s largest meeting for dementia research. The findings offer a first glimpse into the future for Alzheimer’s patients with treatments like Lekempi, which is currently given by injection twice a month.
The drug is a monoclonal antibody that targets toxic plaques in the brain called amyloid, a hallmark of Alzheimer’s disease, to slow the progression of the disease during its early stages. Lekme also works by removing protofibrils, the building blocks of amyloid plaques.
The data show the importance of early and sustained treatment for people with the notoriously difficult-to-treat brain disorder — even after medication has successfully cleared a patient's amyloid plaque.
“Continuing treatment is important if you want to maintain cognition and function for a longer period of time,” Kramer said.
Although Lekumbi is not a cure, he said, “if you start early enough, it can give you years of benefit.”
Kramer added that Eisai believes patients could eventually switch to a maintenance dose of Lekmebi after about 18 to 24 months of treatment, which could be a less frequent or more convenient way to take the drug for a long time.
Eisai and Biogen are seeking regulatory approval for a once-monthly injection of Lekme, with a decision expected in January. The companies also aim to bring to market an injectable form of Lekme that patients could take at home once a week.
“These two things will change the paradigm, they will make it easier for the patient, they will make it easier for the entire medical system,” Kramer said in an interview.
Nearly 7 million Americans have the condition, and it's the fifth leading cause of death among adults over age 65, according to the Alzheimer's Association. By 2050, the number of people with Alzheimer's is expected to rise to nearly 13 million in the United States.
Long-term study details
The findings are based on extensive research conducted on some participants in mid-stage and late-stage clinical trials of Leqembi.
A phase 3 trial, called Clarity AD, was conducted in three different groups of patients for 36 months.
One group of participants took Lekme for three full years, while another group received a placebo for 18 months before switching to Eisai for the same period. Eisai monitored a final group of patients outside the trial who did not receive any treatment for three years.
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Patients who started taking Lekmebe early continued to benefit from the drug for three years, and showed a slower rate of cognitive decline than the other two groups, according to a presentation by Eisai.
The gap in cognitive decline between the “early onset” Lekumbi group and patients who received nothing throughout the study period widened between 18 and 36 months, according to Kramer.
“Likmbi interrupts the natural progression of the disease, and its impact becomes greater and greater,” he added, adding that “the earlier it is detected, the better.”
Patients who started on the placebo saw a slower rate of cognitive decline after switching to Lekmebi after 18 months. But their Alzheimer's disease was worse than in the group who started taking Lekmebi earlier at 36 months.
A substudy of the trial looked at patients who had no or very low levels of another protein that builds up in the brain called tau, which is a marker of the severity of Alzheimer's disease. People with low levels of this protein are in the early stages of the disease.
After three years of taking Lekme, 59 percent of people with very low levels of tau saw no improvement in their Alzheimer’s disease at all, according to the presentation. In fact, more than half of those patients saw improvement in their condition.
Meanwhile, a phase II clinical trial, called Study 201, examined patients who temporarily stopped treatment with Lekme.
Over 18 months, one group of participants took Lekempe, while another group received a placebo. Both groups then took nothing for an average of two years before all patients began treatment with Lekempe for another 18 months.
According to the presentation, the positive effect of licimbo on the patient's disease persisted even after he stopped treatment.
But the rate of cognitive decline in patients who stopped taking Lekmebi returned to that of people taking a placebo during the cessation period. This suggests that even when the amyloid plaques are removed, the disease continues to progress when a patient stops taking Lekmebi, Eisai said in a statement.
“The concept is that if you stop, it will get worse,” Kramer said.
