Eisai drug means breakthrough in therapy against early Alzheimer's disease

Interview with Prof. Frank Jessen

The Japanese pharmaceutical company Eisai, together with the US biotechnology company Biogen, has announced that the antibody Lecanemab, which they developed jointly with Prof. Lars Lannfelt and the Swedish biotech company Bioartic, shows a significant effect against cognitive decline in early-stage Alzheimer's disease.

This result gives scientists and sufferers a sigh of relief. For the first time, the clinical course of Alzheimer's disease could be significantly and robustly slowed down by means of an antibody. In the trial, 1795 participants with mild cognitive impairment and mild dementia due to Alzheimer's disease received the anti-amyloid beta (Aβ) protofibril antibody lecanemab. People with a wide range of comorbidities such as hypertension, diabetes, heart disease, obesity, kidney disease and anticoagulants were eligible. 

Compared to the placebo control group, significant stabilization in clinical outcome in terms of slowing of cognitive and functional decline by 27% occurred in the lecanemab group after 18 months. Also, there was a clear decrease in the amyloid proteins in the brain.

Prof. Jessen, how do you assess the results of the phase 3 study by Eisai and Biogen?

For us clinicians working with Alzheimer’s disease patients, the result of the study is a breakthrough and we are eagerly awaiting the detailed study results. With this antibody, we would have an active substance in our hands for the first time in the search for effective therapies against Alzheimer's, with which we could really intervene causally in the disease process.

How do you classify the 27 percent slowing of decline in the clinical course of the disease?

The primary clinical measure in this study, the so-called CDR-SB (Clinical Dementia Rating scale - Sum of Boxes) is an interview with the patients and the caregivers covering main aspects of cognition and daily functioning.  As such, this instrument describes meaningful changes in the disease course. The CDR-SB is also the recommended outcome scale by the regulatory agencies FDA and EMA. There is general consensus that a slowing on the CDR-SB of around 30% by a disease modifying drug is clinically meaningful. As such, the study demonstrated a real clinical benefit for the patients. In addition, other measures which looked at cognition and daily functioning in more detail showed the same effects. Of course, this does not amount to a cure, but after an early Alzheimer's diagnosis, we would now have the possibility for the first time to meaningfully slow down the course of the disease. For persons diagnosed with early Alzheimer's, this would mean a gain in quality of life.

One of the problems with the last known antibody studies against Alzheimer's was frequent side effects. What is the situation with lecanemab?

Amyloid antibodies may cause mostly transient changes in the brain, which can be observed on MRI and are referred to as ARIA. According to current knowledge, they originate from changes in brain tissue fluids and minor vascular leakage. In most cases, these MRI changes do not cause any symptoms. Sometimes mild symptoms, such as dizziness or headache occur. Severe side effects only occurred in very rare cases. While with some antibodies, the frequency of ARIA is up to 30% of all treated patients, they seem to occur less frequently with lecanemab. In the future, this will probably mean that lecanemab treatment will be monitored with MRI.

How soon can the antibody Lecanemab come onto the market and who will benefit from it?

Eisai and Biogen have already announced that they will apply for approval both in the USA via the FDA and in Europe via the EMA. So, if everything goes well, treatment with lecanemab could be possible already in 2023. Importantly, this type of therapy will only be applied in people who receive an early Alzheimer's diagnosis. There is currently no evidence that lecanemab will work in more advanced stages with more advanced loss of brain cells and tissue. That is why our goal now must be to make the right diagnosis as early as possible. Then we have a real chance of substantially slowing the deterioration of the brain caused by Alzheimer's.

Further information

Prof. Frank Jessen is group leader at the DZNE and director of the Department of Psychiatry and Psychotherapy at the University of Cologne. At the DZNE, he coordinates the DELCODE study, among others. In this study, high-risk patients from memory outpatient clinics are examined with the aim of better predicting the course of Alzheimer's disease and developing new disease markers. He is also the lead author of the S3 guideline Dementias in Germany.

He is a member of several committees, including the steering committee of the European Alzheimer's Disease Consortium (EADC), the National Institute on Aging-Alzheimer's Association (NIA-AA) working group for the development of the Alzheimer's research criteria, and the ISTAART Advisory Council.

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