Updated: Jun 27
Alzheimer's disease is a brain disorder that slowly robs individuals of their memories and identity, impairing the lives of both the patient and those around them. This devastating condition causes progressive cognitive and behavioral problems, leading to difficulties in daily functioning and eventually total dependence on caregivers. As the most common cause of dementia, it accounts for 60-80% of all cases, and currently affects approximately 50 million people worldwide. To date, no definitive treatment has yet been discovered, but exciting news emerged in the field of Alzheimer's disease research in early January.
A cutting-edge biotechnology called "Lenacenab'' has been discovered, offering a glimmer of hope for a better future in the fight against this ravaging disease. Developed by the Japanese pharmaceutical company Eisai in collaboration with the american biotechnology company Biogen, “Lecanemab” is a drug that is reported to have the ability to significantly slow the rate of cognitive decline in people suffering from Alzheimer's disease. This major discovery marks the first time that a drug has shown a proven ability to slow the progression of the disease.
According to Dr.Billy Dunn, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research,“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease.” The current drugs, such as Aricept [donepezil], were developed 20 years ago, and are only cognitive enhancers, meaning that they are intended to improve cognitive function by stimulating neurotransmitters in the brain. However, they are not designed to slow or stop the disease progression in the way that Lecanemab does.
How does Lecanemab work?
As a monoclonal antibody, Lecanemab is made in a laboratory out of a single cell that is cloned to produce identical copies of the antibody. It is administered by intravenous infusion that targets a protein called beta-amyloid, which is considered one of the leading causes of Alzheimer's disease. Amyloid, also known as beta-amyloid protein, is a toxic protein in the brain that accumulates and forms abnormal clusters inside neurons.
This protein is known to interrupt synaptic communication, a communication process between two neurons through the use of chemical messengers called neurotransmitters. In other words, this protein acts as a "disconnector" for communication between neurons by hindering the transmission of chemical signals across the synapse. Its primary effect is to impede the re-uptake of choline, a molecule that stimulates the action of acetylcholine, one of the most important neurotransmitters involved in memory. By blocking and preventing the formation of this neurotransmitter, messages cannot be communicated from one neuron to another, resulting in neurological dysfunction for the patient. Over time, amyloid also causes a series of other toxic processes that further damage the brain.
Lecanemab binds to the beta-amyloid protein and then triggers an immune response in the brain that targets and removes this abnormal protein. Clinical trials have proven that when amyloid is cleared by Lecanemab in the early stages of the disease, the disease progresses more slowly, allowing individuals to maintain their cognition and independence longer.
What are the clinical trial results?
The study indicates overwhelmingly positive results for Lecanemab. About 1,795 people aged 50 to 90 with early-onset Alzheimer's disease ─ mild cognitive impairment or mild dementia due to Alzheimer’s disease ─ participated in the Phase III clinical study conducted in several centers in North America, Europe, and Asia. Participants were randomly assigned in a 1:1 ratio to receive intravenous Lecanemab (10 mg per kilogram of body weight every 2 weeks) or a placebo. The 897 individuals who were administered the placebo experienced a significant decline in their cognitive function, indicated by an average increase of 4.6 points in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score. In contrast to the placebo group, the group that received Lecanemab showed an increase of only 1.8 points in their CDR-SB score, indicating a 27% reduction in cognitive decline. This group also exhibited a decrease in beta-amyloid burden, as determined by PET scans, and showed improved scores on other cognitive tests.
Although Lecanemab does not provide a complete cure for Alzheimer's disease, these results are encouraging for patients, their families, and care providers.
Possible side effects?
Lecanemab is not without potential risks. Another recent study has reported incidence rates of sometimes severe and more frequent side effects than in the placebo group. Antibodies that enter the brain and trigger an immune response to remove a substance can increase "Amyloid Related Imaging Abnormalities" (ARIA). ARIA can manifest in two forms: ARIA-E, which causes brain swelling or edema, and ARIA-H, which provokes microscopic bleeding. However, as Dr. Sharon Cohen notes, "It is important to note that the rate of ARIA with Lecanemab is low - 12,5 % for ARIA-E et 17 % for ARIA-H" with symptoms occurring in only a small percentage of cases and typically resolving spontaneously with appropriate management and monitoring.
Despite having potential side effects, Lecanemab was approved by the FDA on January 6th, 2023. The approval of Lecanemab may seem like a departure from the usual rules. Regulatory agencies typically require two conclusive studies before approving a drug. In the case of the new technology, both trials were not completed, and the second failed to meet the required clinical criteria. Yet the FDA permitted the use of this drug via the Accelerated Approval pathway, which is a quick method to approve medications for severe conditions involving an unmet medical need when no actual treatment has yet been discovered. At this point, a drug can be accepted even if it has not fulfilled all the requirements.
Nonetheless, Lecanemab represents a significant step forward in the development of Alzheimer's treatments and has the potential to improve the lives of millions of people suffering from this debilitating disease. While there are some potential side effects, the low rate of ARIA and the ability to manage and monitor these effects offer hope for a safe and effective treatment option.