New Phase 3 trial results show that lecanemab, an experimental drug, has “potential” to be used as an Alzheimer’s treatment. However, the findings raise safety concerns due to their association with serious adverse events.
Lecanemab is one of the most experimental drugs for dementia that has been shown to slow cognitive decline.
Two months ago, drugmakers Biogen, and Eisai, announced that lecanemab was able to reduce cognitive decline and functional decline by 27% in Phase 3.
The Phase 2 trial in Alzheimer’s patients did not show any significant differences between lecanemab or a placebo over 12 months. However, the Phase 3 trial data shows that lecanameb is associated with greater cognitive decline and better amyloid clearance at 18 months.
Researchers wrote that lecanemab was effective in reducing brain amyloid levels in people with early Alzheimer’s. It was also associated with fewer clinical measures of cognition, function, and decline than placebo over 18 months. However, it was associated with adverse effects. To determine the safety and efficacy of lecanemab for early Alzheimer’s disease, longer trials are needed.
Tuesday’s statement by the Alzheimer’s Association stated that it is encouraged and welcomes all Phase 3 data.
These peer-reviewed and published results prove that lecanemab can give patients more time to live independently and participate in everyday life. This could allow patients to recognize their spouses, children, and grandchildren for many more months. It states that treatments that provide tangible benefits for people with mild cognitive impairment (MCI) or early Alzheimer’s disease are just as effective as those that prolong the lives of patients with other terminal diseases.
Clearing out the amyloid
From March 2019 to March 2021, the Phase 3 trial took place at 235 locations in North America and Europe. The trial involved 1,795 people between 50 and 90 with mild cognitive impairment from early Alzheimer’s or mild Alzheimer’s disease-related dementia.
The placebo was given to the rest.
Researchers found that both groups had an average clinical dementia rating (or CDR-SB score) of about 3.2 at the trial’s beginning. This score is consistent in early Alzheimer’s disease. A higher number can be associated with cognitive impairment. The CDR-SB score increased by 1.21 points over 18 months in the lecanemab treatment group, as opposed to 1.66 in the placebo.
“Significant differences emerge as soon as the six-month timepoint,” Dr. Christopher van Dyck (author of the study, and director of Yale Alzheimer’s Disease Research Center), said Tuesday at a conference in San Francisco.
He stated that the lecanemab treatment had met both primary and secondary endpoints.
Monoclonal antibodies such as lecanemab can be used to bind to amyloid beta. This is a hallmark of degenerative brain disorders. The average amyloid level of participants in the lecanemab and placebo groups was 77.92 centroids, respectively.
The researchers discovered that the average amyloid level fell by 55.48 centroids over 18 months in the lecanemab-treated group and rose by 3.64 centroids for the placebo group.
These results show that “lecanemab could make a clinically significant difference for people with Alzheimer’s disease in the early stages” according to Dr. Lynn Kramer (chief clinical officer of Alzheimer’s disease and brain health at Eisai).
The trial ended with 6.9% of trial participants who were in the lecanemab treatment group discontinuing the trial because of adverse events, as compared to 2.9% in the placebo group. Overall, serious adverse events occurred in 14% of lecanemab participants and 11.3% in the placebo group.
The most frequent adverse events in this drug group were reactions to intravenous injections and abnormalities in their MRIs. These include brain swelling and bleeding, also known as Amyloid-related imaging abnormalities or ARIA.
“Lecanemab was generally tolerated well. During Tuesday’s conference, Dr. Marwan Sabbagh (author of the study, and professor at the Barrow Neurological Institute) stated that the most common adverse events were infusion-related reactions. He said that these events were resolved in a matter of months.
ARIA brain bleeding was observed in 17.3% of patients who received lecanemab, and 9% in those who received a placebo. According to trial data, ARIA brain swelling was found in 12.6% of those who received lecanemab, and 1.7% with a placebo.
ARIA can lead to permanent impairment or hospitalization for some people. ARIA was more common in those who were carriers of APOE4, a gene that can increase your risk of Alzheimer’s and other dementias. Researchers wrote that ARIA was numerically less common among APOE4 carriers.
Researchers also reported that 0.7% of participants in lecanemab groups died and 0.8% in placebo groups. This corresponds to six deaths in lecanemab and seven in placebo groups. They wrote that no deaths were attributed to lecanemab and/or ARIA.
According to a news release, the company plans to file for the approval of the drug in the United States at the end of March. Lecanemab has been granted priority review by the US Food and Drug Administration.
According to the FDA, Eisai’s Biologics license application for lecanemab was accepted by the FDA in July. This approval is part of the accelerated pathway. This program allows drugs to be approved earlier for serious conditions or “fill an unmet need”, while drugs are being tested in larger, more extensive trials.
The FDA will grant traditional approval if the clinical trials prove that the drug has a clinical benefit. If the FDA does not find benefit in the confirmatory trials, they have regulatory procedures that could allow the FDA to take the drug off the marketplace.
According to the Alzheimer’s Association states, “The FDA will decide whether to grant accelerated approval for lecanemab before January 6, 2023.” The FDA could make this decision, but the current Center for Medicare and Medicaid Services policy will stop thousands or even thousands of Medicare beneficiaries living with terminal, progressive diseases from having access to the treatment in the timeframe they have. Medicare must support patients who decide that the treatment is right for them.
“This is only the first chapter”
“If and when the FDA approves this drug, it will take clinicians some times to be able to understand how this drug may be effective in their patients,” Dr. Richard Isaacson, an adjunct professor of neurology at Weill Cornell Medicine who is not involved with studying lecanemab’s development or study, stated.
He said that while the data from Phase 3 was encouraging, it is still unclear how it will translate into clinical practice.
According to the majority of doctors, they are desperate for any therapy that could help their patients. Four of my family members have Alzheimer’s disease. Isaacson stated that if a relative asks me if I should be taking this drug, and if the dose is right for them, and there are no side effects, then yes. Isaacson said, “I think even an important option.”
He said that the experimental drug is an example of personalized medicine in America, especially for Alzheimer’s disease. Genetic testing can be used in clinical practice to determine the APOE gene, which will allow for better patient care.
He said, “This is only the first chapter of what I hope will become a long-running book in disease-modifying treatments for Alzheimer’s disease.”
According to the Alzheimer’s Association, more than 300 Alzheimer’s treatments have been approved for clinical trials.
The first known case of Alzheimer’s disease was discovered in 1906 by Dr. Alois Alzheimer. He found changes in brain tissue in a woman with memory loss, language difficulties, and unpredictable behavior. This debilitating condition now affects over 6 million Americans.
Although there is no cure for Alzheimer’s disease, there are many prescription drugs that can be used to manage the symptoms. The FDA approved Aduhelm last year for the early stages of Alzheimer’s. The FDA had not approved any novel treatment for this condition since 2003.
Lecanemab is being evaluated as an Alzheimer’s treatment, but it is not a cure for the condition, according to Tara Spires-Jones, deputy director of the Centre for Discovery Brain Sciences at the University of Edinburgh.
Spires-Jones, a UK-based Science Media Centre spokesperson, stated that both groups had worsening symptoms. However, people who took the drug didn’t experience a decline in cognitive abilities. To be certain that this treatment is safe and effective, we will need to conduct more trials.
Bart De Strooper (director of the UK Dementia Research Institute), stated that Alzheimer’s is still a “complex” condition in general. This statement was distributed by Science Media Centre.
We still have much to learn about the causes. De Strooper said that it is important to continue investing in discovery research. “We may also be able to identify new targets for which therapies we could use in conjunction with an anti-amyloid drug like lecanemab.” He is a consultant for several pharmaceutical companies including Eisai but has not been consulted on lecanemab.
He said, “This trial shows that Alzheimer’s can be treated.” I hope that we will see a change in the underfunding of dementia research. I am looking forward to a future in which we can treat this and other neurodegenerative disorders with a variety of medications that are tailored to each patient’s needs.