FDA Decision on Donanemab for Alzheimer’s Expected by End of Year

Eli Lilly has completed its FDA submission for full approval of donanemab to treat patients with early Alzheimer’s disease. Regulatory action expected by end of year. A Lilly spokesperson would not provide a specific date but was confident about the timeline.

The submission is supported by data from the phase 3 TRAILBLAZER-ALZ 2 study. Full results from the trial show that donanemab slowed cognitive and functional decline in people with early symptomatic Alzheimer’s disease. Almost half of participants at earlier stage of disease on donanemab had no clinical progression at one year. Additionally, analyses of patients at earliest stage of the disease had even greater benefit, with 60% slowing of decline compared with placebo.

The data were shared at the 2023 Alzheimer’s Association International Conference and also published in the Journal of the American Medical Association.

Liana G. Apostolova, M.D.

“These results demonstrate that diagnosing and treating people earlier in the course of Alzheimer's disease may lead to greater clinical benefit,” Liana G. Apostolova, M.D., distinguished professor in Alzheimer’s Disease research and professor in neurology, radiology, medical and molecular genetics at Indiana University School of Medicine, said in a press release. “The delay of disease progression over the course of the trial is significant and will give people more time to do such things that are meaningful to them.”

Alzheimer’s disease is a neurodegenerative disease and the most common form of dementia. It is characterized by plaques of the beta-amyloid protein and tangles of a protein called tau. Donanemab specifically targets deposited amyloid plaque.

The TRAILBLAZER-ALZ 2 enrolled participants with a broad range of cognitive scores and amyloid levels. Participants were stratified by their level of tau, a predictive biomarker for disease progression. Among all participants, treatment with donanemab reduced amyloid plaque on average by 84% at 18 months, compared with a 1% decrease for participants on placebo. Participants were able to stop taking donanemab once they achieved pre-defined criteria of amyloid plaque clearance. About half of participants met this threshold at 12 months and about seven of every 10 participants reached it at 18 months.

Among participants with low-to-medium levels of tau, donanemab treatment slowed cognitive decline by 35% on integrated Alzheimer’s Disease Rating Scale, which measures cognitive ability and activities of daily living. Donanemab slowed decline by 36% on the Clinical Dementia Rating-Sum of Boxes, a widely used scale for dementia staging.

Among all amyloid-positive early symptomatic patients, treatment with donanemab slowed decline by 22% on the integrated Alzheimer’s Disease Rating Scale and 29% on Clinical Dementia Rating-Sum of Boxes.

In terms of safety, 17.4% of patients in the donanemab the group experienced any serious adverse event compared with 15.8% in the placebo group. Infusion-related reactions were experienced by 8.7% of patients in the donanemab group.

The incidence of amyloid-related imaging abnormalities (ARIA) was consistent with the previous TRAILBLAZER-ALZ study. ARIA occurs across the class of amyloid plaque clearing antibody therapies. It is most commonly observed as temporary swelling in an area or areas of the brain (ARIA-E) or as microhemorrhages or superficial siderosis (ARIA-H). These may be serious and even fatal in some cases. Among patients in the donanemab group, 36.8% of patients experienced any ARIA.

Related: FDA Issues Complete Response for Lilly Alzheimer’s Drug

The FDA had previously said it wouldn’t grant accelerated approval of donanemab to treat patients with early Alzheimer’s disease. In a complete response letter in January 2023, the agency indicated that there too few patients with at least 12 months of data provided in Lilly’s submission.