Alzheimer’s Drug Breakthrough Hailed as ‘Momentous’

An 18-month randomised controlled trial of the new Alzheimer’s drug lecanemab has been hailed as “momentous” after encouraging Phase III trial results. The effects, while moderate, stand in contrast to virtually all other Alzheimer’s drug development efforts which have ended in failure.

According to the trial results published in the New England Journal of Medicine, lecanemab slows the rate of progression of Alzheimer’s by about 25%, though it is only really effective if the disease is caught early. Cognitive assessment scores as well as positron-emission tomography (PET) imaging of amyloid showed benefits.

This may be of great benefit to those who already know that they are already at risk of the disease, such as actor Chris Hemsworth who, at age 39, is taking a break from acting after he discovered that he has a high genetic risk of Alzheimer’s.

At present, the only FDA-approved drug to slow the progression of Alzheimer’s, Aduhelm, is of questionable benefit at best, is exorbitantly expensive and there has been an official probe into alleged irregularities in its approval process.

The 1975 trial participants were 50–90 years old with early Alzheimer’s disease (mild cognitive impairment or mild dementia due to Alzheimer’s disease) with evidence of amyloid on PET or by cerebrospinal fluid testing. Participants were randomised to receive intravenous lecanemab (10mg/kg of body weight every 2 weeks) or placebo.

The primary end point was the change from baseline at 18 months in the score on the Clinical Dementia Rating–Sum of Boxes (CDR-SB; range, 0 to 18, with higher scores indicating greater impairment). Key secondary end points included change in amyloid burden on PET, and on other cognitive impairment assessment scores.

 The mean CDR-SB score at baseline was approximately 3.2 in both groups. The adjusted least-squares mean change from baseline at 18 months was 1.21 with lecanemab and 1.66 with placebo. In a substudy involving 698 participants, there were greater reductions in brain amyloid burden with lecanemab than with placebo. Other cognitive assessments favoured lecanemab as well. Lecanemab resulted in infusion-related reactions in 26.4% of the participants and amyloid-related imaging abnormalities with oedema or effusions in 12.6%.