Promising treatment for Alzheimer’s disease reported at Clinical Trials on Alzheimer’s disease (CTAD) Conference
At an Alzheimer’s disease research conference last week, new clinical trial data was presented for an antibody drug candidate called lecanemab. (Read more about the development of lecanemab here.)
An antibody is a natural protective protein in blood that recognizes and binds to specific targets, such as those associated with virus infections. This specific antibody was designed to remove toxic amyloid deposits from the brains of people with Alzheimer’s disease.
Researchers have long theorized that anti-amyloid treatments could slow the progression of Alzheimer’s disease. The recently released data shows that, indeed, lecanemab does remove amyloid plaque from the brain. (Read the full journal article and data here.)
Lecanemab was tested in very rigorous, large clinical trials conducted by treating people with early stage Alzheimer’s disease for 18 months, while evaluating the effects of the treatments on removal of amyloid deposits, as well measuring for changes in memory function and behavior.
The main objective of the lecanemab’s clinical trials was to show that treatment with the antibodies could slow disease progression, when compared to patients receiving placebo.
The results for lecanemab treatment presented at the conference and published in the New England Journal of Medicine this week are considered to be the strongest evidence for effectiveness to slow the disease progression ever achieved in Alzheimer’s disease.
How do researchers know lecanemab works?
Lecanemab was tested by comparing treatment and placebo in about 1800 patients, half of whom received lecanemab by monthly infusion for 18 months and half of whom received saline infusions for 18 months (placebo group).
The data analyzed show that the lecanemab-treated group showed very robust and complete amyloid plaque clearance from brain associated with significantly reduced disease progression (about 27%), measured through cognitive assessments, compared to the placebo group. In addition, the lecenemab-treated group showed slower loss of functioning for activities associated with daily life (about 37%). The company believes the clinical benefit will translate to patients treated with lecanemab having several more months living independently and recognizing their families and friends.
Do researchers believe lecanemab is safe?
The research indicates that treatment with lecanemab was generally safe, although all antibodies that clear amyloid plaques from brain are associated with risks of brain bleeding and brain swelling. Determining the safety of a newly developed drug is always complex, and that is especially true for anti-amyloid antibody treatments, which impact the brain. Both of these antibodies are associated with a low incidence (10-20%) of swelling and bleeding in brain, called ARIA.
Most of the ARIA does not produce symptoms for patients, but a small fraction of ARIA are symptomatic, causing headache, confusion, or dizziness, for example; but the symptoms are temporary and do not appear to be dangerous.
In rare cases, brain bleeding can be more significant and life threatening, and two deaths associated with brain bleeding during the lecanemab trial are under investigation. In both cases, the patients were taking inhibitors of blood clotting (called anticoagulants, typically taken for heart disease), while also being treated with lecanemab, and it is likely that the anticlotting drugs contributed to the severity of the brain bleeding and death.
These incidents will be further analyzed and discussed by experts and with the FDA before the drug “label,” or its use and use requirements, are determined during the drug approval process. It is possible that before lecanemab can be widely used, the FDA will prohibit the use of anticoagulants during treatment with lecanemab.
What happens next?
It is likely that, along with data from earlier clinical trials of lecanemab, the new data will lead to FDA approval of lecanemab for treating early stage Alzheimer’s disease.
The clinical trial data showing the effective use of lecanemab to combat the progression of Alzheimer’s disease is a leap forward in Alzheimer’s treatment. But before lecanemab is prescribed to or used by people with Down syndrome who have Alzheimer’s disease, there are several more hurdles to be addressed.
What does this mean for people with Down syndrome who have an Alzheimer’s diagnosis?
As far as we know, no one with Down syndrome was included in the lecanemab trials. Which means, no one knows if the drug would have the same effect, side effects, and/or risks when administered to people with Down syndrome.
Although the drug’s efficacy could very well be the same (since the biology of Alzheimer’s disease in people with Down syndrome is physiologically similar to the general population), it is very difficult to measure clinical efficacy because the standard assessment tools used in clinical trials to determine cognitive function cannot be applied to people with Down syndrome. Assessments will have to be developed specifically for the Down syndrome population.
In addition, the safety of the drug for people with Down syndrome must still be determined. This will require a separate safety study, as adults with Down syndrome may be at higher risk with this class of therapy because they have higher rates of seizures than the general population.
Will the Lecanemab treatment be reimbursed?
After FDA decides on approval of the drug in 2023, CMS will then decide whether the drug is reimbursed under Medicare and Medicaid. As LuMind IDSC and its partners from the United Down Syndrome Coalition did earlier this year during the CMS reimbursement decision for Aduhelm, we plan to closely monitor the upcoming reimbursement decision for Lecanemab for how the decision affects people with Down syndrome.
What else was presented at the Alzheimer’s conference?
Results from other large clinical trials were also presented for anti-amyloid therapies gantenerumab, aduhelm, and donanemab, further generating important data for the research field on understanding the anti-amyloid antibodies therapy class of drugs. Not every drug candidate in this class have the same effect on amyloid plaques, cognition, function and side effects so it is important to look at each drug independently. Also, researchers presented information showing continued progress for blood tests for diagnosing Alzheimer’s.