The Use of Lacanemab in the Treatment of Alzheimer’s Disease

 by Annika Bright

There are now over 55 million people diagnosed with Alzheimer’s Disease (AD). Due to the cause of the formation of the amyloid plaques being largely unknown, researchers have discovered it to be a challenging process to find an effective treatment for the disease. However, the newly-trailled drug, Lecanemab has been proven to slow down the rate of neurodegeneration through the clearance of β-amyloid protofibrils (accumulation of amyloid beta) in the early stages of the disease, as they begin to form. The drug is comprised of an antibody (BAN2401) which binds specifically to the β-amyloid protofibrils which are subsequently destroyed. Therefore, the reduced load of amyloid beta would reduce the characteristic symptoms of AD. As a result of the clinical trials during Phase One which involved volunteers with mild AD, the researchers observed no significant difference in the amyloid load before and after treatment with Lacanemab. This conclusion was achieved through analysis of the Cerebrospinal Fluid (CBF) which acts as a marker to determine the  β-amyloid load due to the fact that it comes into contact with the extracellular brain fluid. 

Conversely, Phase Three resulted in an alternative conclusion. A vast 1,900 patients enrolled in the trial who similarly, had developed mild to moderate AD. There was an average β-amyloid protein level of 77.92 centiloids in the actively treated group and an average of 75.03 centiloids in the placebo group. After 18 months of a 10’mg/kg weekly dose, the average amyloid level of the active treatment group fell significantly to 55.84 centiloids whereas the placebo group’s average amyloid level increased to 78.67 centiloids (which followed the normal AD trajectory). From this, we can observe that although there is not a complete eradication of the β-amyloid protein in the brain, there was a reasonable decline in the deposited protein load, which ultimately slowed the progression of neuronal death and cognitive decline. Thus, BAN2401 acts as a method to prolong life rather than a cure to Alzheimer’s Disease. 

However, during the trial, 14% of the participants experienced abnormal side-effects commonly known as Amyloid related imaging abnormalities (ARIA). Examples include brain haemorrhaging, as well as swelling of the brain. These were stated not to be caused by Lecanemab directly but rather, due to the adverse effects of the MRI imaging as well as inserting the drug intravenously. On the contrary, if a larger sample size was used it is unknown as to whether ARIA complications would result in more extreme effects on the overall population with AD. 

To conclude, it is shown that Lecanemab would be more effective is in earlier stages of the disease as less β-amyloid would be apparent in the brain and thus, could act as a treatment for these patients. However, in more severe stages of the disease is could be argued that the complications of ARIA outweigh the prolonging of life as bleeds in the brain could lead to hospitalisation. Furthermore, in Phase One of the trial, where patients were observed over 12 months, there was no large difference between the use of a placebo and the use of Lecanemab - only when used for 18 months in Phase Three was there an apparent improvement in β-amyloid levels. It is certain that the development of Lacanemab will continue to improve research into future AD treatments.