Study Suggests Lecanemab is a Potential Treatment Option for Early Alzheimer’s Disease

The Director of Yale’s Alzheimer’s Disease Research Unit, Christopher H. van Dyck, MD, and colleagues conducted a pivotal phase III study to evaluate the use of lecanemab—a monoclonal antibody that targets the toxic protein amyloid-beta—in patients with early Alzheimer’s disease. Although the dementia drug has demonstrated “potential” as a treatment for Alzheimer’s, the results of this study still raise some safety concerns due to the drug’s correlation with specific serious adverse events. Their study was published in The New England Journal of Medicine. 

The accumulation of aggregated amyloid-beta is often responsible for the progression of pathological processes in Alzheimer’s Disease. Whereas the phase II trial did not show a significant difference between lecanemab and a placebo in Alzheimer’s disease patients at 12 months, phase III data found that lecanemab correlated with more amyloid clearance and less cognitive decline at 18 months. 

“These peer-reviewed, published results show lecanemab will provide patients more time to participate in daily life and live independently. It could mean many months more of recognizing their spouse, children and grandchildren,” said The Alzheimer’s Association in a statement. “Treatments that deliver tangible benefits to those living with mild cognitive impairment due to Alzheimer’s and early Alzheimer’s dementia are as valuable as treatments that extend the lives of those with other terminal disease.”

Funded by Eisai and Biogen, this double-blind trial enrolled 1,795 patients 50 to 90 years of age with early Alzheimer’s disease—defined as mild cognitive impairment or mild dementia due to Alzheimer’s disease—with evidence of amyloid accumulation. Participants were randomly assigned to receive intravenous lecanemab (n = 898) or placebo (n = 897). The primary endpoint was a change from baseline to 18 months in the score on the Clinical Dementia Rating–Sum of Boxes (CDR-SB). Secondary enpoints included the change in amyloid burden, as well as scores on the Alzheimer’s Disease Composite Score (ADCOMS), the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog14), and the Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL). 

Despite a mean CDR-SB score of 3.2 at baseline in both groups, there was a significant change from baseline to 18 months with lecanemab versus placebo (P < .001). Notably, lecanemab treatment was associated with improved ADAS-cog14 (P < .001), ADCOMS (P < .001), and ADCS-MCI-ADL (P < .001) scores. Moreover, the average amyloid level dropped 55.48 centiloids in the lecanemab group and went up 3.64 centiloids in the placebo group at 18 months. Despite these improvements, adverse events were prevalent in this patient population. 

Infusion-related reactions affected 26.4% of patients on treatment, with approximately 6.9% and 2.9% of patients discontinuing treatment of lecanemab and placebo, respectively. Furthermore, serious adverse events affected 14% of patients in the lecanemab group and 11.3% in the placebo group. For many patients, amyloid-related imaging abnormalities included brain bleed (17.3% vs. 9%) and brain swelling (12.6% vs. 1.8%) in both the lecanemab and placebo arms. 

Of note, the frequency of these events appeared to be increased in individuals who harbored the APOE4 gene, which is often related to an increase in risk of Alzheimer’s and other dementias. Additionally, the investigators stated that six of participants in the lecanemab group and seven of those in the placebo group died. Despite this, an NPR press release suggests that Alzheimer’s patients and their families are already anticipating the arrival of lecanemab since it has been a very long road to find proper treatments.

Alzheimer’s disease was first documented in 1906 by Dr. Alois Alzheimer, who observed changes in the brain tissue of a woman who had memory loss, language problems, and unpredictable behaviors. Today, this disease affects approximately 6 million people in the United States. With no cure,  there are several prescription drugs available to help manage symptoms. According to CNN, the FDA approved Aduhelm in 2021 for early phases of Alzheimer’s disease. Aduhelm was the first new treatment approved for Alzheimer’s since 2003, and was the first therapy that targets the fundamental pathophysiology of the disease.

“This trial proves that Alzheimer’s disease can be treated,” said Bart De Strooper, MD, PhD, director of the UK Dementia Research Institute. “I hope we will 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 medications adapted to the individual needs of our patients.”

References:

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