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(CNN) --
The experimental drug lecanemab shows "potential" as a treatment for Alzheimer's disease, according to the results of the new Phase 3 trial, but the findings raise some safety concerns because of its association with certain serious adverse events.
Lecanemab has become one of the first experimental dementia drugs that appears to slow the progression of cognitive decline.
The long-awaited trial data, published Tuesday in the New England Journal of Medicine, comes about two months after drugmakers Biogen and Eisai announced that lecanemab had been found to reduce cognitive and functional decline by 27% in its phase 3 trial.
A Phase 2 trial did not show a significant difference between lecanemab and placebo in patients with Alzheimer's disease at 12 months, but data from the Phase 3 trial suggest that at 18 months, lecanameb was associated with increased amyloid clearance and less cognitive decline.
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"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. researchers.
"Longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer's disease."
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The Alzheimer's Association said in a statement Tuesday that it welcomes and is further encouraged by the complete data from Phase 3.
“These published and peer-reviewed results show that lecanemab will provide patients with more time to participate in daily life and live independently.
It could mean many more months of recognizing your spouse, children, and grandchildren.
Treatments that provide tangible benefits to people living with mild cognitive impairment (MCI) due to Alzheimer's disease and early Alzheimer's dementia are just as valuable as treatments that prolong life for people with other terminal illnesses ”, said the Association.
Elimination of amyloid, key in Alzheimer's
The Phase 3 trial was conducted at 235 sites in North America, Europe and Asia from March 2019 to March 2021. It involved 1,795 adults, ages 50 to 90, with mild cognitive impairment due to Alzheimer's disease. Early or Dementia related to Alzheimer's disease.
About half of the participants were randomly assigned to receive lecanemab, given intravenously every two weeks, and the rest received a placebo.
The researchers found that participants in both groups had a "clinical dementia score" or CDR-SB score of approximately 3.2 at the start of the trial.
Such a score is consistent with early Alzheimer's disease, with a higher number associated with more cognitive decline.
At 18 months, the CDR-SB score increased 1.21 points in the lecanemab group, compared to 1.66 in the placebo group.
"Significant differences emerge as early as the six-month time point," study author Dr. Christopher van Dyck, director of the Yale University Alzheimer's Disease Research Center, said Tuesday during a presentation at Alzheimer's Disease Clinical Trials Conference in San Francisco.
“The 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 disorder.
At baseline, the average amyloid level of the participants was 77.92 centyloids in the lecanemab group and 75.03 centyloids in the placebo group.
At 18 months, the average amyloid level decreased by 55.48 centyloids in the lecanemab group and increased by 3.64 centyloids in the placebo group, the researchers found.
Based on these results, "lecanemab has the potential to make a clinically meaningful difference for people living with the early stages of Alzheimer's disease and their families by slowing cognitive and functional decline," said Dr. Lynn Kramer, clinical director of Alzheimer's disease and brain health at Eisai, in a statement.
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About 6.9% of trial participants in the lecanemab group discontinued the trial due to adverse events, compared with 2.9% of those in the placebo group.
Overall, serious adverse events occurred 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 intravenous infusions and MRI abnormalities, such as swelling and bleeding in the brain called amyloid-related imaging abnormalities, or ARIA.
“Lecanemab was generally well tolerated.
Most of the adverse events were infusion-related reactions, ARIA-H and ARIA-E, and headache,” study author Dr. Marwan Sabbagh, a professor at the Barrow Neurological Institute, said during the conference on Tuesday.
He added that such events were resolved within months.
ARIA cerebral hemorrhage occurred in 17.3% of those receiving lecanemab and 9% of those in the placebo group.
ARIA brain inflammation was documented in 12.6% with lecanemab and 1.7% with placebo, according to trial data.
Some people who get ARIA may not have symptoms, but it can sometimes lead to hospitalization or lasting impairment.
And the frequency of ARIA events 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 events "were numerically less common" among non-APOE4 carriers, the researchers wrote.
The researchers also wrote that about 0.7% of participants in the lecanemab group and 0.8% of those in the placebo group died, corresponding to six documented deaths in the lecanemab group and seven in the group. of placebo.
“The investigators did not consider any deaths to be related to lecanemab or to occur with ARIA,” they wrote.
They approve an experimental medicine against Alzheimer's 1:32
The company intends to apply for US approval of the drug by the end of March, according to its press release.
The US Food and Drug Administration has given lecanemab "priority review."
In July, the FDA accepted Eisai's biologic license application for lecanemab under the accelerated approval track, according to the company.
The program allows for early approval of drugs that treat serious conditions and "fill an unmet medical need" while the drugs are studied in larger, longer trials.
If trials confirm that the drug provides clinical benefit, the FDA grants traditional approval.
But if the confirmatory trial shows no benefit, the FDA has regulatory proceedings that could lead to removing the drug from the market.
“The FDA is expected to decide whether to grant accelerated approval for lecanemab by January 6, 2023,” the Alzheimer's Association statement reads.
“If the FDA were to do this, current [Centers for Medicare & Medicaid Services] policy will prevent thousands upon thousands of terminally and progressively ill Medicare beneficiaries from accessing this treatment within the limited window of time they will have to access it.
If a patient decides with their health care provider that a treatment is right for them, Medicare should support that as it does beneficiaries with any other disease."
"This is only the first chapter"
“When and when the FDA approves this drug, it will take some time for physicians to be able to analyze how this drug may or may not be effective in their own patients,” especially since APOE4 gene carriers could be at higher risk of side effects, said Dr. Richard Isaacson, an adjunct associate professor of neurology at Weill Cornell Medicine, who is not involved in the study of lecanemab or its development.
"While this study is certainly encouraging, how it translates into clinical practice, real-world clinical practice, remains to be seen," he said of the data from the phase 3 trial.
In general, “doctors are hungry for any possible therapy that can 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 medication?'
In the right patient, at 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," Isaacson said.
"I would say even a major option."
He added that the experimental drug serves as an example of the significant 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 the approach to caring for a patient.
“This is just the first chapter of what I hope will become a really long book on disease-modifying therapies for Alzheimer's disease,” he said.
More than 300 Alzheimer's treatments are in clinical trials, according to the Alzheimer's Association.
Alzheimer's, a complex disease
Alzheimer's disease was first documented in 1906, when Dr. Alois Alzheimer discovered changes in the brain tissue of a woman who had memory loss, language problems, and unpredictable behavior.
The debilitating disease now affects more than six million adults in the United States alone.
There is no cure for Alzheimer's disease, but several prescription medications are available to help control 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 condition 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 Center for Discovery Brain Sciences 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 decline as much in their cognitive abilities," Spires-Jones said in a written statement distributed by the UK-based Science Media Center.
"Longer trials will be needed to make sure that the benefits of this treatment outweigh the risks."
Overall, Alzheimer's remains a "complex" disease, Bart De Strooper, director of the UK's Institute for Dementia Research, 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 by doing so we may also identify new targets for which we can develop therapies that we could use in combination with anti-amyloid drugs such as lecanemab," said De Strooper, who is a consultant for a a number of pharmaceutical companies, including Eisai, but has not inquired about lecanemab.
“This trial shows that Alzheimer's disease can be treated,” he said.
“I hope we start to see a reversal in the chronic underfunding of dementia research.
I look forward to a future in which we treat this and other neurodegenerative diseases with a battery of drugs tailored to the individual needs of our patients."
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