Lilly's Alzheimer's Drug Donanemab Injection Nominated for Priority Review in China

On November 14, the CDE website showed that the marketing application for Eli Lilly's new Alzheimer's disease (AD) drug Donanemab Injection has been proposed for priority review. It is intended for the treatment of early symptomatic Alzheimer’s disease, including mild cognitive impairment due to Alzheimer’s disease and mild Alzheimer’s disease. Notably, the marketing application for Donanemab Injection was accepted by the CDE on October 31.

Donanemab is a monoclonal antibody that binds to the N3pG subtype of beta-amyloid protein. It can bind to beta-amyloid protein deposited in the brains of Alzheimer's disease patients, thereby promoting the clearance of amyloid plaques in the patient’s brain. In the second quarter of 2023, Eli Lilly and Company resubmitted the marketing application for Donanemab to the FDA to seek accelerated approval.

In May this year, Eli Lilly announced that the Phase III TRAILBLAZER-ALZ 2 study of Donanemab for the treatment of patients with early symptomatic Alzheimer's disease had met its primary endpoint. The results showed that Donanemab significantly slowed cognitive decline in patients with early symptomatic AD. Nearly half of the participants (47%) did not experience disease progression within one year (defined as no decline in clinical dementia rating), compared to 29% in the placebo group.

TRAILBLAZER-ALZ 2 is a randomized, double-blind, placebo-controlled Phase III clinical trial, with the primary analysis population (n=1182) being patients with moderate levels of tau protein and pronounced AD clinical symptoms. The primary endpoint is the change in scores on the Alzheimer's Disease Composite Score (iADRS, which assesses cognitive abilities and activities of daily living) from baseline to 18 months. Key secondary endpoints include changes in scores on the Clinical Dementia Rating-Sum of Boxes (CDR-SB, which evaluates cognitive function), the Alzheimer’s Disease Cooperative Study – Activities of Daily Living Inventory (ADCS-iADL), and the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) from baseline to 18 months.

Results showed that, compared with the placebo group, the decline in iADRS scores was slowed by 35% (p<0.0001) in patients receiving donanemab; at 18 months, the rate of decline in CDR-SB scores in the donanemab group was 36% slower than in the placebo group (p<0.0001); ADCS iADL scores indicated that disease progression in the donanemab group was delayed by 40% at 18 months (p<0.0001). Additionally, donanemab reduced the risk of patients progressing to the next stage of the disease by 39% (HR=0.61; p<0.001).

After pooling the results of the moderate tau level population with the higher tau level population (n=552) (n=1736), the donanemab treatment group still demonstrated positive outcomes across all clinical endpoints (p<0.001), with the rate of decline in CDR-SB and iADRS scores slowed by 29% and 22%, respectively.

In terms of safety, 24% of participants in the donanemab group experienced amyloid-related imaging abnormalities-edema (ARIA-E), with a symptomatic ARIA-E rate of 6%; 31.4% of patients in the donanemab group had cerebral microhemorrhages and superficial siderosis (ARIA-H), compared to 13.6% in the placebo group. The majority of ARIA cases were mild to moderate in severity, with a serious ARIA rate of 1.6%, including two participants who died from ARIA and one patient who died after experiencing severe ARIA; 8.7% of patients had infusion-related reactions, most of which were mild to moderate.

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