The experimental drug lecanemab shows “potential” as a treatment for Alzheimer’s disease, according to results released on Wednesday (30) from the phase 3 clinical trial, but the results raise some safety concerns due to its association with certain events serious adverse events.
Lecanemab became one of the first experimental dementia drugs to appear to slow the progression of cognitive decline.
The long-awaited study data, published in the New England Journal of Medicine, comes about two months after drugmakers Biogen and Eisai announced that lecanemab reduced cognitive and functional decline in 27% of participants in their phase 3 study.
A phase 2 study did not show a significant difference between lecanemab and a placebo in patients with Alzheimer’s disease over 12 months – but data from the phase 3 study suggest that, at 18 months, lecanemab was associated with more amyloid clearance and less cognitive decline.
“In people with early Alzheimer’s disease, lecanemab reduced brain amyloid levels and was associated with less decline in clinical measures of cognition and function than placebo at 18 months, but was associated with adverse events,” the researchers wrote.
“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 on Tuesday that it welcomes and encourages the full Phase 3 data.
“These published and peer-reviewed results show that lecanemab will provide patients with more time to participate in daily life and live independently. That could mean many more months of acknowledgment from your spouse, children, and grandchildren. Treatments that provide tangible benefits for those living with mild cognitive impairment (MCI) due to Alzheimer’s disease and early Alzheimer’s dementia are just as valuable as treatments that extend the lives of people with other terminal illnesses.”
clearing the amyloid
The phase 3 study was conducted at 235 sites in North America, Europe and Asia from March 2019 to March 2021. It enrolled 1795 adults, ages 50 to 90, with mild cognitive impairment due to early Alzheimer’s disease or mild dementia related to Alzheimer’s disease.
About half of the participants were randomly assigned to receive lecanemab, given intravenously every two weeks, and the others received a placebo.
The researchers found that participants in both groups had a “clinical dementia rating” or CDR-SB score of about 3.2 at baseline.
This score is consistent with early Alzheimer’s disease, with a higher number associated with more cognitive impairment. At 18 months, the CDR-SB score was up 1.21 points in the lecanemab group, compared with 1.66 in the placebo group.
“Significant differences emerge as early as six months,” said Dr. Christopher van Dyck, study author and director of the Yale Alzheimer’s Disease Research Center, said Tuesday during a presentation at the Alzheimer’s Disease Clinical Trials Conference in San Francisco.
“Treatment with lecanemab achieved both primary and secondary endpoints,” he said.
Lecanemab, a monoclonal antibody, works by binding to beta-amyloid, a hallmark of the degenerative brain disorder. At baseline, the average amyloid level of participants was 77.92 centiloids in the lecanemab group and 75.03 centiloids in the placebo group.
At 18 months, the mean amyloid level had dropped by 55.48 centiloids in the lecanemab group and had risen by 3.64 centiloids in the placebo group, the researchers found.
Based on these results, “lecanemab has the potential to make a clinically significant difference for people living in the early stages of Alzheimer’s disease and their families by delaying cognitive and functional decline,” Dr. Lynn Kramer, clinical director of Alzheimer’s disease and brain health at Eisai, said in a press release.
About 6.9% of study participants in the lecanemab group discontinued the study due to adverse events, compared with 2.9% of those in the placebo group. Overall, there were serious adverse events in 14% of the lecanemab group and 11.3% of the placebo group.
The most common adverse events in the drug group were reactions to the intravenous infusions and abnormalities on their MRI scans, such as brain swelling and brain bleeding, called amyloid-related imaging abnormalities (ARIA).
“Lecanemab was generally well tolerated. The majority of adverse events were infusion-related reactions, ARIA-H and ARIA-E, and headache,” said Dr. Marwan Sabbagh, study author and professor at the Barrow Neurological Institute, during Tuesday’s conference.
He added that such events were resolved within months.
ARIA cerebral bleeding was observed among 17.3% of those receiving lecanemab and 9% of those in the placebo group; ARIA brain swelling was documented in 12.6% with lecanemab and 1.7% with placebo, according to study data.
Some people suffering from ARIA may not experience symptoms, but occasionally it can lead to hospitalization or lasting impairment.
And the frequency of ARIA appeared to be higher in people who had a gene called APOE4, which can increase the risk of Alzheimer’s disease and other dementias. ARIA “were numerically less common” among non-APOE4 carriers, the researchers wrote.
The researchers also wrote that approximately 0.7% of participants in the lecanemab group and 0.8% of participants in the placebo group died, corresponding to six documented deaths in the lecanemab group and seven in the placebo group.
“No deaths were considered by investigators to be lecanemab-related or occurred with ARIA,” they wrote.
The company intends to apply for the drug’s approval in the United States by the end of March, according to its press release. The US Food and Drug Administration has granted “priority review” to lecanemab.
In July, the FDA accepted Eisai’s Biological License Application for lecanemab under the accelerated approval process, according to the company.
The program allows for early approval of drugs that treat serious illnesses and “fill an unmet medical need” while the drugs are being studied in larger, longer trials.
If tests confirm that the drug offers a clinical benefit, the FDA grants traditional approval. But if confirmatory testing does not show benefit, the FDA has regulatory procedures that could lead to the drug being withdrawn from the market.
“The FDA is expected to decide whether to grant accelerated approval to lecanemab by January 6, 2023,” the Alzheimer’s Association statement reads.
“Should the FDA do so, current policy [do Centro de Serviços Medicare e Medicaid] will prevent thousands upon thousands of Medicare beneficiaries with a terminal and progressive illness from accessing this treatment within the limited amount of time they will have to access it. If a patient decides with their doctor that a treatment is right for them, Medicare should support them, as it does beneficiaries with all other illnesses,” he adds.
“This is just the first chapter”
“If and when this drug is approved by the FDA, it will take physicians some time to analyze how this drug may or may not be effective in their own patients,” especially as APOE4 gene carriers may be at greater risk for side effects, said the Dr. Richard Isaacson, an adjunct associate professor of neurology at Weill Cornell Medicine, who is not involved in the lecanemab study or its development.
“While this study is certainly encouraging, it remains to be seen how this translates into real-world clinical practice,” he said of the Phase 3 study data.
Overall, “doctors are hungry for any possible therapy that might help our patients. I have four family members with Alzheimer’s disease. If I have a family member who comes to me and says, ‘Should I take this drug?’ In the right patient, in the right dose, for the right duration, with proper and careful monitoring of side effects, yes, I would suggest that this drug is a viable option,” said Isaacson.
“I would even say an important option.”
He added that the experimental drug serves as an example of the important need for personalized medicine in the United States, especially when it comes to Alzheimer’s disease, such as the use of genetic testing in clinical practice to identify the APOE gene to better individualize one’s approach to care. of the patient.
“This is just the first chapter of what I hope will become a really long book on Alzheimer’s disease-modifying therapies,” he said.
More than 300 Alzheimer’s treatments are in clinical trials, according to the Alzheimer’s Association.
Alzheimer’s disease was first documented in 1906 when Dr. Alois Alzheimer discovered changes in the brain tissue of a woman suffering from memory loss, language problems and unpredictable behavior.
The debilitating disease now affects more than 6 million adults in the United States.
There is no cure for Alzheimer’s disease, but there are several prescription medications available to help manage the 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 therapy for the disease since 2003.
Although lecanemab is being tested as an Alzheimer’s drug, it is not a cure, said Tara Spires-Jones, deputy director of the Brain Sciences Discovery Center at the University of Edinburgh, who was not involved in the study.
“Both groups in the trial had worsening symptoms, but people taking the drug did not suffer as much decrease in their cognitive abilities,” Spiers-Jones said in a written statement distributed by the UK-based Science Media Centre.
“Longer trials will be needed to ensure that the benefits of this treatment outweigh the risks,” he added.
Overall, Alzheimer’s remains a “complex” disease, Bart De Strooper, director of the UK Dementia Research Institute, said in a statement distributed by the Science Media Centre.
“We still have a lot to learn about the underlying causes. It is therefore imperative that we continue to invest in discovery research and, in doing so, we can also identify new targets for which we can develop therapies that we can use in combination with anti-amyloid drugs such as lecanemab,” said De Strooper, who is a consultant to a number of pharmaceutical companies, including Eisai, but has not consulted on lecanemab.
“This trial proves that Alzheimer’s is treatable,” he said. “I hope we start to see a reversal in the chronic underfunding of dementia research. I look forward to a future where we treat this and other neurodegenerative diseases with a battery of drugs tailored to the individual needs of our patients.”,
Source: CNN Brasil
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