Pharmaceutical giant Eli Lilly has submitted its Alzheimer’s disease drug candidate, donanemab, for FDA review and has released additional clinical data supporting its application. The drug is an anti-amyloid antibody designed to target and break up plaques of amyloid beta, a protein that accumulates in the brain during the progression of Alzheimer’s. The clinical data shows that donanemab slowed the decline associated with the disease by 35% in patients with intermediate levels of tau protein, another characteristic of Alzheimer’s. In patients with low-to-medium levels of tau, representing an earlier stage of the disease, the drug led to a nearly 39% reduction in disease progression, equivalent to a delay of between 4.4 and 7.5 months in cognitive and functional decline compared to those receiving a placebo. The results were presented at the Alzheimer’s Association International Conference in Amsterdam and published in the Journal of the American Medical Association.
Mark Mintun, Group Vice President of Neuroscience Research & Development at Lilly, emphasized the importance of early treatment of Alzheimer’s based on the data, stating that going early should be able to slow the disease even more. Donanemab’s Phase 3 trial enrolled 1,736 patients with early symptoms of Alzheimer’s and signs of amyloid and tau. Study participants were stratified based on tau levels, and those assigned to receive donanemab were allowed to stop treatment once they achieved predetermined amyloid clearance criteria. The company reported that about half of the patients who received the study drug met this benchmark at 12 months, and seven out of every ten participants reached it at 18 months.
The trial met its main objective by showing a slowing in decline in the intermediate tau group. In a pre-specified analysis of a subgroup of patients with low-to-medium tau, Donanemab demonstrated even greater benefits, with a 60% reduction in decline in those with mild cognitive impairment. On the Clinical Dementia Rating-Sum of Boxes (CDR-SB) scale, which is used to assess Alzheimer’s patients, the drug slowed decline by 46% based on the Integrated Alzheimer’s Disease Rating Scale in the low-to-medium tau group. In patients with mild dementia, the decline was slowed by 38% on the CDR-SB scale and by 30% on the Integrated Alzheimer’s Disease Rating Scale. However, patients with high levels of tau, representing a more advanced stage of Alzheimer’s, did not experience the same benefit.
The FDA submission for donanemab has been completed, and Lilly is preparing to seek regulatory approvals in other markets as well. A decision from the FDA is expected by the end of the year. Whether donanemab will become the second anti-amyloid antibody to win full regulatory approval remains to be seen but its potential to slow the progression of Alzheimer’s provides hope for patients and the medical community.
July 18, 2023
Artificial Intelligence
FDAcop
