Reacción a "Reactions: data from Alzheimer's clinical trial with lecanemab antibody published"

The Clarity study is a phase III, multicentre, randomised, double-blind, phase III clinical trial testing the anti-amyloid monoclonal antibody lecanemab compared to placebo in patients with early-stage Alzheimer's disease. 

The clinical trial demonstrates its main objective: there is less cognitive and functional impairment in the treatment arm compared to the placebo arm. Using the CDR-SB scale (ranging from 0 to 18; a higher value means greater cognitive and functional impairment), patients in the placebo arm have an average increase of 1.66 points over the 18-month follow-up, while those treated with lecanemab only have an increase of 1.21 points. The study also shows that lecanemab treatment significantly reduces amyloid accumulation in the brain. Finally, lecanemab treatment is also better than placebo on all secondary endpoints studied, including other cognitive scales and biological biomarkers. In conclusion, this is a well-designed, rigorous study that points to a beneficial effect of lecanemab in the early stages of Alzheimer's disease. 

Lecanemab, unlike other anti-amyloid antibodies, has a special affinity for soluble amyloid protofibrils, which probably have a toxic effect in the brain. This feature is possibly one of the reasons for its good results.  

While it is true that the study shows less cognitive decline in patients treated with lecanemab, the clinical relevance will have to be determined. A difference of 0.45 on the CDR-SB scale, which ranges from 0 to 18, may seem minor. However, small changes in cognition can have a big impact not only on patients' autonomy, but also on their caregivers. On the other hand, we should bear in mind that the trial investigates the effect of the drug after 18 months of administration. Longer studies will have to be carried out to determine the long-term effect. 

The aim of this study is not only to determine the efficacy of the drug, but also its safety. There is no difference in the number of deaths or total number of adverse events between the lecanemab arm and the placebo arm. However, there is a higher proportion of amyloid-related imaging abnormalities (ARIA). Although these abnormalities are not serious in most cases, they need to be studied in detail. Also, it has recently been reported that two people included in the trial died. Whether these deaths are attributable to the drug or to other reasons needs to be studied. As Alzheimer's is a heterogeneous disease, it will be important to determine which patients can potentially benefit most from this treatment and which of them have a higher risk of side effects. The same study shows that it is patients with allele 4 of the APOE gene who are most at risk of adverse effects in the form of ARIA. Treatment and doses administered to these patients will probably need to be individualised.