What is the new drug?
▪  Lecanemab is a monoclonal antibody that binds to the abnormal proteins seen in early Alzheimer’s disease and helps to remove it from the brain. It has been in clinical trials since 2010.

What was the study?
▪  This was an 18-month phase 3 trial called Clarity AD that enrolled 1,795 people who had Mild Cognitive Impairment or mild Alzheimer’s disease.

What were the results?
▪  Those in the treatment group had a significantly slower rate of cognitive decline compared to the placebo group. The primary outcome measure was the CDR-SB, a commonly used scale that measures the severity of Alzheimer’s symptoms in six areas, ranging from memory to daily activities to problem solving. Results indicated that the lecanemab treatment reduced cognitive decline by 27% compared to the placebo group.
▪  There were also significant results for other outcome measures, including the drug’s ability to remove amyloid from the brain and several other measures of cognition and daily functioning.
▪  A remaining question is how clinically meaningful the effect is. The change is small, and the study was only 18 months long. More information is needed to know how much this will mean to patients and their families.

Things to know:
▪  The study included a large number of people (1,795) and the researchers were able to recruit a diverse sample of participants (25% were non-white).
▪  Side effects: Removing amyloid from the brain may cause edema (brain swelling or ARIA-E) or new microhemorrhages (bleeding in the brain or ARIA-H). These same amyloid related imaging abnormalities (ARIA) were seen in the previous study of aducanumab. However, the frequency of ARIA observed on neuroimaging in the lecanemab trial seems to be lower. The frequency of adverse events (e.g. nausea, confusion, headache) was low: 2.8% for ARIA-E in the treatment group and 0.7% for ARIA-H in the treatment group.
▪  The full data has not been released, so we cannot yet see the details of the outcome measures or the side effects. For example, we do not know how many people may have dropped out of the study due to serious ARIA side effects.
▪  This study only included people who already had cognitive symptoms, so it is unclear whether this treatment will prevent or delay the onset of cognitive symptoms in those who are at risk. However, that is being studied in the AHEAD trial here at Mount Sinai which is testing the same drug in people at risk but with no cognitive symptoms.

Next steps?
▪  In November 2022, specific clinical data from this study will be released. The ADRC will send an update after this meeting.
▪  Eisai has applied to have an accelerated approval of this drug, which could happen as early as January 2023.

Bottom line:
▪  There is potential for this treatment to benefit a specific subset of individuals with Alzheimer’s disease: those who are amyloid positive, have mild symptoms and do not have any medical conditions that might exclude them (e.g., significant vascular illness).
▪  Many questions remain:
      ▪  Is this a treatment that if given early would change the course of the illness?
      ▪  Would it need to be given for the duration of the illness once symptoms were present?
      ▪  Would there be other populations (e.g., more impaired individuals or asymptomatic individuals, or people with other medication conditions) that this drug might benefit?
      ▪  Further studies will need to assess whether these findings, if observed over the course of the illness, will be associated with significantly lower burden for patients and caregivers.

As always, we here at the ADRC are here to answer your questions either about these new findings, or about any of our ongoing studies at Mount Sinai.

Email:
Margaret.Sewell@mssm.edu

Phone:
212-241-8329