Lecanemab is effective across endpoints with “highly statistically significant results” large Phase 3 trial demonstrates, but will benefit outweigh questions?
Earlier today, Eisai announced the results from its large global Phase 3 confirmatory Clarity AD clinical study of lecanemab, an investigational anti-amyloid beta (Aβ) protofibril antibody for the treatment of mild cognitive impairment (MCI) due to Alzheimer’s disease and mild Alzheimers with confirmed presence of amyloid pathology in the brain.
Longevity.Technology: Eisai’s Clarity AD was a global confirmatory Phase 3 placebo-controlled, double-blind, parallel-group, randomised study in 1,795 people who received a bi-weekly infusion of either lecanemab or a placebo. Interestingly, eligibility criteria allowed patients with a broad range of comorbidities/comedications, including anti-coagulants, and a recruitment strategy of diversity meant that 4.5% and 22.5% of the randomised participants in the US were Black and Hispanic, respectively.
These results, which were published in the New England Journal of Medicine, demonstrate that lecanemab was able to slow the rate of cognitive decline by 27% over 18 months and improve ability to undertake day-to-day activities, but they come hot on the heels of news of a lecanemab-related death.
The participants had a clinical dementia score of approximately 3.2 at the beginning of the trial, a rating consistent with early Alzheimer’s – the higher the score, the higher the degree of cognitive impairment. After 18 months, the score of the lecanemab-dosed participants had gone up 1.21 points compared with a greater rise of 1.66 in the placebo group .
Lecanemab is a monoclonal antibody, and it functions as a drug by binding to amyloid beta, chemically ‘sticky’ peptides that clump together to form plaques that are evident in the brains of those suffering from Alzheimer’s. Amyloid plaques are thought to block cell-to-cell signaling at synapses and trigger dangerous inflammation and so are a focus for Alzheimer’s drug research.
At the start of the lecanemab study, the participants’ average amyloid level was measured and found to be 77.92 centiloids in the dosed group and 75.03 centiloids in the placebo group. At the 18 month mark, the average amyloid level dropped 55.48 centiloids in the lecanemab group, whereas it had continued to rise in the placebo group, going up 3.64 centiloids .
“Based on the Clarity AD results, the investigational anti-amyloid beta protofibril antibody lecanemab has the potential to make a clinically meaningful difference for people living with the early stages of Alzheimer’s disease and their families by slowing cognitive and functional decline,” said Lynn Kramer, MD, Chief Clinical Officer, Alzheimer’s Disease and Brain Health at Eisai .
However, it’s not all rosy in the lecanemab garden; the adverse events suffered by some participants continue to raise questions about the safety of the drug.
The two most common adverse events were reactions to the intravenous infusions and abnormalities detected on their MRI brain scans, including brain swelling (13% of participants) and brain bleeds (17%), although Eisai said lecanemab’s amyloid-related imaging abnormalities incidence profile was “within expectations” based on the Phase 2b results. Overall, 6.9% of the trial participants in the drug group stopped the trial due to adverse events.
Longer trials will be needed to determine the efficacy and safety of lecanemab in early Alzheimer’s disease, and since the drug is targeted at the early disease stages, it needs to go hand-in-hand with early screening and diagnosis – if your brain has accumulated enough disease-related damage for you to be showing symptoms, lecanemab is not currently a drug that can help you.
Cautious optimism remains the order of the day; The Alzheimer’s Association said in a statement earlier that it welcomes and is further encouraged by the full Phase 3 data.
“These peer-reviewed, published results show lecanemab will provide patients more time to participate in daily life and live independently,” says the Association. “It could mean many months more of recognizing their spouse, children and grandchildren. Treatments that deliver tangible benefits to those living with mild cognitive impairment (MCI) due to Alzheimer’s and early Alzheimer’s dementia are as valuable as treatments that extend the lives of those with other terminal diseases .”