Advancing Alzheimer’s care: a novel therapy with lecanemab

Abstract

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects the patient’s quality of life. The current regime of drugs only halts the symptoms of the disease, and the underlying pathology remains untouched; thus, there is progressive deterioration due to the intact pathology. Various drugs are being researched to address the complex neuropathology of AD. The FDA has approved lecanemab, which has shown considerable efficacy in reducing Aβ plaque, thereby addressing the pathology. Of the monoclonal antibodies being explored for AD, lecanemab has shown higher selectivity towards Aβ and better efficacy in clinical improvement. The phase III trials have demonstrated clinical improvement of mild AD upon biweekly intravenous administration of 10 mg/kg. This improvement was assessed using the primary and secondary endpoints such as Clinical Dementia Rating-Sum of Boxes (CDR-SOB), Mini-Mental State Examination (MMSE), and Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Apart from the infusion-related reactions with lecanemab, it is also associated with amyloid-related imaging abnormalities (ARIA), which are uniquely seen in monoclonal antibodies for AD as it is also seen in solanezumab and aducanumab. ARIA may be dose-dependent as with lower doses, the incidence was lower, and it is associated with microhemorrhages, hemosiderosis, or edema. Monoclonal antibodies such as aducanumab, agantenerumab have shown questionable efficacy; thus, their clinical use is debatable even though aducanumab has received FDA approval. Although solanezumab met some secondary endpoints, its benefit is similar to the placebo. Currently, efficacy is only proven for monotherapy with lecanemab; therefore, neurologists may need to discontinue adjuvant treatment. Clinical improvement in women and ApoE4 carriers is also questionable; further studies are required to prove its efficacy in these groups. Various studies are being conducted to find the efficacy of drugs targeting the complex pathology of AD, such as the tau targeting E2814, E2025 and E2511 protecting the cholinergic neurons, TREM2 agonists P522R prevent the microglial dysfunction. These drugs are noteworthy as they can be the possible combination of lecanemab. Further studies are required to prove lecanemab’s efficacy in moderate-to-severe AD and its combination with other drugs.

Keywords

• Monoclonal antibodies
• Lecanemab
• Alzheimer’s
• Dementia
• Neurodegeneration and beta-amyloid