Promising trial results for the anti-amyloid monoclonal lecanamab in early Alzheimer’s disease have been given a cautious welcome by dementia researchers.
The drug was shown to reduce cognitive decline by 27% in patients with early stage Alzheimer’s disease and also reduce amyloid levels in the brain according to phase 3 trial results from the released by Eisai and Biogen.
The Clarity AD randomised controlled trial which involved 1,795 people with early AD, showed that lecanemab treatment (10 mg/kg bi-weekly) met the primary endpoint and reduced clinical decline on the global cognitive and functional scale, CDR-SB (Clinical Dementia Rating-Sum of Boxes), compared with placebo at 18 months, with a treatment difference in the score change of -0.45 (p=0.00005) in the analysis of intent-to-treat (ITT) population.
Lecanemab treatment showed highly statistically significant changes in CDR-SB from baseline compared to placebo starting as early as six months.
Key secondary endpoints including amyloid level changes also showed highly statistically significant results compared with placebo. These were change from baseline at 18 months in amyloid levels in the brain measured by amyloid positron emission tomography (PET), the AD Assessment Scale-cognitive subscale14 (ADAS-cog14), AD Composite Score (ADCOMS) and the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL).
The incidence of amyloid-related imaging abnormalities-edema/effusion (ARIA-E), and ARIA-H (ARIA cerebral microhaemorrhages, cerebral macrohaemorrhages, and superficial siderosis) was 21.3% in the lecanemab group and 9.3% in the placebo group, which was within expectations, according to the company.
Dr Catherine Mummery, Consultant Neurologist, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, UK, said the lecanemab CLARITY results were “exciting” and the clearest indicator to date that targeting amyloid levels in the brain could slow cognitive decline.
“The results are consistent in size with those found in earlier phase trials with other anti amyloid drugs, and with the positive, controversial trial in aducanumab. This convergence strengthens the findings,” she said.
However, she added that the size of the effect was small and that in practice the drug would have to be used early in the course of Alzheimer’s disease, raising questions about how patients would be identified and selected for treatment.
“What we cannot know yet is whether that effect increases over time in an individual; that would be predicted but is untested – time will tell,” she said
Professor Rob Howard, Professor of Old Age Psychiatry, UCL, said the unambiguously statistically positive result “represents something of an historic moment when we see the first convincing modification of Alzheimer’s disease” but said it would be important to see the full trial details released at the Clinical Trials On Alzheimer’s Congress in November.
“Having shown efficacy, the next question is whether there is clinical effectiveness. A 0.45 point advantage on an 18-point scale, where the accepted minimum worthwhile difference ranges from 0.5 to 1.0 points, will mean that there are going to be some very difficult conversations and decisions in the next weeks and months,” he said.
In a statement, Biogen and Eisei said the results for lecanemab were being submitted to the FDA for priority review under the accelerated approval pathway in an effort to secure approval as soon as possible, and a review was expected in January 2023.