The positive outcome of Eli Lilly’s 18 months phase 3 randomized clinical trial on donanemab among 1736 participants with early Alzheimer disease (mild cognitive impairment/mild dementia) with amyloid and low/medium or high tau pathology was simultaneously presented and published at Alzheimer’s Association International Conference in Amsterdam and the journal JAMA respectively.
Donanemab, an antibody designed to clear brain amyloid plaque, significantly slowed disease progression at 76 weeks by 35%. Lequembi, FDA’s recently approved drug, is known to reduce the progression by 27%.
The uniqueness of this study was that patients were off the drug once the plaques cleared. Plaques did not reappear during the remaining period of the study, and the beneficial effects on memory and thinking persisted. Therefore unlike Leqembi, patients might not need monthly intravenous infusions of Donanemab, thereby reducing side effects and treatment cost. The duration of this benefit is, however, not known yet. Advanced cases showed less beneficial effect suggesting earlier treatment intervention is more likely to have a positive outcome.
Like other amyloid modifying therapies Donanemab also resulted in amyloid-related imaging abnormalities (ARIA) in about 25% of those treated with the drug. Three participants with serious ARIA died. Among other side effects, 6% of Donanemab treated group complained of headache, nausea and confusion.
While this potential drug is not a cure to Alzheimer’s disease, early intervention will slow the progression of the disease among patients. Lily has already submitted the results to FDA. By the end of this year we will know whether Donanemab receives FDA clearance.
