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Investigational drug lecanemab shows “potential” as a treatment for Alzheimer’s disease, according to results from a new phase III trial, but its association with certain serious adverse events suggests that the findings are not safe. has raised concerns.
Lecanemab became one of the first experimental dementia drugs that appeared to slow the progression of cognitive decline.
The long-awaited trial data published in the New England Journal of Medicine on Tuesday show that pharmaceutical companies Biogen and Eisai found that lecanemab reduced cognitive and functional decline by 27% in a phase 3 trial. About two months after the announcement.
Although a phase 2 trial showed no significant difference between lecanemab and placebo at 12 months in patients with Alzheimer’s disease, data from a phase 3 trial showed that lecanemab was more effective than amyloid at 18 months. Many suggest that it was associated with clearance and a reduction in cognitive decline.
“In patients with early Alzheimer’s disease, lecanemab reduced brain amyloid levels and reduced clinical measures of cognition and function at 18 months less than placebo, but was associated with adverse events,” the researchers said. writes. “Longer trials are needed to determine the efficacy and safety of lecanemab in early Alzheimer’s disease.”
The Alzheimer’s Association said in a statement Tuesday that it welcomed and was further encouraged by the full Phase 3 data.
“These peer-reviewed and published results show that lecanemab provides patients with more time to participate in daily life and live independently. , which means it takes many more months to recognize grandchildren. Treatments that have specific benefits for people with mild cognitive impairment (MCI) due to Alzheimer’s disease or early Alzheimer’s dementia are not available in other end-stages. It is as valuable as a life-extending treatment for people with the disease.”
The Phase 3 trial was conducted from March 2019 to March 2021 at 235 sites across North America, Europe and Asia. 1,795 adults aged 50 to 90 with mild cognitive impairment due to early Alzheimer’s disease or mild Alzheimer’s disease-related dementia participated.
Approximately half of the participants were randomly assigned to receive intravenous lecanemab every two weeks, and the remainder received placebo.
The researchers found that participants in both groups had a “clinical dementia assessment” or CDR-SB score of approximately 3.2 at the start of the study. Such scores are consistent with early Alzheimer’s disease, with higher numbers associated with greater cognitive impairment. By 18 months, he had increased his CDR-SB score by 1.21 points in the lecanemab group compared to 1.66 points in the placebo group.
Dr. Christopher Van Dyke, author of the study and director of the Yale Center for Alzheimer’s Disease Research, said in a presentation Tuesday at the Alzheimer’s Disease Clinical Trials Conference in Sun. Francisco.
“Lecanemab treatment met the primary and secondary endpoints,” he said.
Lecanemab, a monoclonal antibody, works by binding to amyloid-beta, a hallmark of degenerative brain damage. Participants’ mean amyloid levels at study entry were 77.92 centroids in the lecanemab group and 75.03 centroids in the placebo group.
By 18 months, the researchers found that mean amyloid levels had fallen by 55.48 centroids in the lecanemab group and increased by 3.64 centroids in the placebo group.
Based on these results, “lecanemab may make a clinically meaningful difference for people with early-stage Alzheimer’s disease and their families by slowing cognitive and functional decline,” said Alzheimer’s. said Lynn Kramer, Ph.D., Chief Clinical Officer, Disease and Brain. Eisai Health, said in a news release.
Approximately 6.9% of study participants in the lecanemab group discontinued the study due to adverse events compared to 2.9% in the placebo group. Overall, serious adverse events occurred in 14% of patients in the lecanemab group and 11.3% in the placebo group.
The most common adverse events in the drug group were reactions to intravenous infusion and MRI abnormalities, such as brain swelling and cerebral hemorrhage, called amyloid-associated imaging abnormalities (ARIA).
“Lecanemab was generally well tolerated. The most adverse events were infusion-related reactions, ARIA-H, ARIA-E, and headache,” said the study’s author and professor at the Barrow Institute of Neurology. Dr. Marwan Sabbagh said at a conference on Tuesday. He added that such incidents were resolved within months.
ARIA cerebral hemorrhages were seen in 17.3% of the lecanemab group and 9% of the placebo group. According to trial data, ARIA brain swelling was recorded in 12.6% with lecanemab and 1.7% with placebo.
Some people who become infected with ARIA have no symptoms, but it can lead to hospitalization and permanent disability. The frequency of ARIA appeared to be higher in people with a gene called APOE4, which increases the risk of Alzheimer’s disease and other dementias. ARIA was “numerically less common” among APOE4 non-carriers, the researchers wrote.
The researchers also wrote that about 0.7% of participants in the lecanemab group and 0.8% of participants in the placebo group died. “Investigators found no deaths to be considered lecanemab-related or caused by ARIA,” they wrote.
The company aims to apply for approval of the drug in the United States by the end of March, according to a news release. The U.S. Food and Drug Administration has granted “priority review” to lecanemab.
In July, the FDA accepted Eisai’s biologics application for lecanemab under the accelerated route, the company said. The program will allow early approval of drugs that treat serious conditions and “fill an unmet medical need,” but the drugs are being studied in larger, longer-term trials.
The FDA grants conventional approval if clinical trials confirm that the drug provides clinical benefit. However, if confirmatory trials fail, the FDA is taking regulatory action that could lead to the drug’s withdrawal from the market.
“The FDA plans to decide whether to grant accelerated approval to lecanemab by January 6, 2023,” said a statement from the Alzheimer’s Association. “If the FDA does, the current [Center for Medicare and Medicaid Services] This policy prevents the thousands of Medicare beneficiaries with terminal progressive disease from accessing this treatment during the limited time they have to access it. Medicare, like all other beneficiaries of the disease, must stand by them. ”
“If this drug is approved by the FDA, it will be some time before clinicians will be able to analyze how this drug works or does not work in individual patients.” Carriers of the APOE4 gene were not involved in the study of lecanemab or its development, said Dr. Richard Isaacson, adjunct associate professor of neurology at Weill Cornell Medicine.
“While this study is certainly encouraging, it remains to be seen how this translates into clinical practice, actual clinical practice,” he said of the Phase 3 trial data.
Overall, “Doctors are hungry for a cure that might help their patients. I have four family members with Alzheimer’s. I would recommend that, in the right patient, at the right dose, for the right duration, with proper and careful monitoring of side effects, yes, this drug is a viable option. “It’s even an important choice.”
He added that the experimental drug serves as an example of the critical need for personalized medicine in the United States, especially when it comes to Alzheimer’s disease. Individualize the appropriate approach. Patient care.
“This is just the first chapter of what I hope to be a very long book on disease-modifying therapies for Alzheimer’s disease,” he said.
According to the Alzheimer’s Association, more than 300 treatments for Alzheimer’s disease are in clinical trials.
Alzheimer’s disease was first documented in 1906 when Dr. Alois Alzheimer discovered changes in brain tissue in a woman with memory loss, speech problems and unpredictable behavior. This debilitating disease now affects her more than 6 million adults in the United States.
There is no cure for Alzheimer’s disease, but there are some prescription drugs that help manage symptoms. Last year, the FDA approved Aduhelm for the early stages of Alzheimer’s disease. Prior to that, the FDA had not approved a new treatment for this condition since 2003.
Lecanemab is being tested as a treatment for Alzheimer’s disease, but not as a cure, said Tara Spiers-Jones, deputy director of the Center for Discovery and Brain Sciences at the University of Edinburgh.
In a written statement circulated by the UK-based Science Media Centre, Spiers-Jones said: “Symptoms worsened in both groups in the trial, but the cognitive decline in those who took the drug was not as great. “Longer trials are needed to confirm that the benefits of this treatment outweigh the risks.”
In general, Alzheimer’s continues to be a ‘complex’ disease, said Bart De Strooper, director of the UK Dementia Research Institute, in a statement distributed by the Science Media Centre.
“There is still much to learn about the underlying causes. Therefore, it is imperative that we continue to invest in discovery research, and in doing so, we will be able to explore the potential for use in combination with anti-amyloid drugs like lecanemab. It is also possible to identify new targets from which therapeutics can be developed.I have consulted for a series of pharmaceutical companies, including Eisai, but have not consulted on lecanemab.
“This trial proves that Alzheimer’s disease can be treated.” We look forward to the future of treating this and other neurodegenerative diseases.”