Experts comment on Lilly drug reported to slow Alzheimer’s progression by 35%

Eli Lilly has announced the results of a phase 3 trial into its Alzheimer’s medicine. The trial showed that donanemab significantly slowed cognitive and functional decline in people with early symptomatic Alzheimer’s disease. It found that for people with early stages of Alzheimer’s there was a 35% reduction in disease progression.

Professor Perminder Sachdev, Scientia Professor of Neuropsychiatry at UNSW Sydney and Co-director of the Centre for Healthy Brain Ageing (CHeBA), commented “This is exciting news. This is the third monoclonal antibody in a row to show positive results and the second to show clinical benefits. The future for the treatment of Alzheimer’s disease is looking increasingly promising. Of course, we need the full data to evaluate it, and the rate of adverse effects is a concern, but I am heartened by the news.”

Dr Ian Musgrave, Senior Lecturer in the Faculty of Medicine, School of Medicine Sciences, within the Discipline of Pharmacology at the University of Adelaide, said “Donanemab is an amyloid plaque–specific antibody, and the recently published clinical trial in participants with early symptomatic Alzheimer’s disease showed clinically significant reductions in disease progression. However, despite near total removal of amyloid plaque, the disease still did progress, although at a much slower rate than without treatment. The patients were also highly selected, and this success may not be as effective in the more general population, and the cost of therapy may be prohibitive. While this result is greatly encouraging, it is clear we still have a lot more work to do to successfully treat Alzheimer’s disease.”

A/Professor Lyndsey Collins-Praino, Head of the Cognition, Ageing and Neurodegenerative Disease Laboratory (CANDL) in the School of Biomedicine at the University of Adelaide, noted “The donanemab Phase 3 study results are potentially promising, as they indicate not only plaque clearance, but also demonstrable slowing of cognitive/functional decline in early symptomatic Alzheimer’s disease across both the primary and multiple secondary endpoints. Encouragingly, 47% of participants showed no progression of disease severity over a 1-year period (compared to 29% on placebo). This is a marked improvement over previous trials of other amyloid-targeting antibodies, which have largely failed to sufficiently demonstrate cognitive benefit. In fact, the clinical approval of such compounds has been met with controversy.

“Despite early promise, however, full evaluation will not be possible until a comprehensive profile of results, particularly safety data, is released for peer review. Concerningly, preliminary results indicate amyloid-related imaging abnormalities (ARIA) in multiple participants (24% ARIA-E and >30% ARIA-H). While most of these were mild-moderate and resolved/stabilised, 1.6% experienced serious ARIA, with 3 deaths (2 attributed to ARIA and one following an incident of serious ARIA). Thus, donanemab is not without potentially significant risk. As treatment was completed once plaque clearance was achieved, questions also remain about long-term benefits, given that cognitive/functional decline is not dependent on plaque pathology alone. While I am cautiously optimistic, key questions remain.”