Lilly Announces Positive Phase III Results for Donanemab in Early Symptomatic Alzheimer’s Disease and Plans Regulatory Submission This Quarter

On May 3, Eli Lilly announced that the Phase III TRAILBLAZER-ALZ 2 study of donanemab for the treatment of early symptomatic Alzheimer's disease (AD) 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%) showed no disease progression within one year (defined as no decline in clinical dementia rating), compared to 29% in the placebo group. Eli Lilly expects to submit a marketing application for donanemab to the FDA this quarter to seek accelerated approval.

After the announcement, Eli Lilly's stock price surged 6%, with its market value exceeding $400 billion, surpassing Novo Nordisk ($378.07 billion) to become the top pure pharmaceutical company by market value.

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 significant AD clinical symptoms. The primary endpoint is the change in the Alzheimer's Disease Composite Score (iADRS, assessing patients' cognitive abilities and activities of daily living) from baseline to 18 months. Key secondary endpoints include changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB, assessing patients' cognitive abilities), the Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS-iADL) score, and the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) score 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 the donanemab-treated group; at 18 months, the rate of decline in CDR-SB scores was reduced by 36% (p<0.0001) in the donanemab group versus the placebo group; ADCS iADL scores indicated that disease progression was slowed by 40% (p<0.0001) in the donanemab group at 18 months. Additionally, donanemab reduced the risk of patients progressing to the next stage of the disease by 39% (HR=0.61; p<0.001).

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

In terms of safety, 24% of subjects 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 subjects who died from ARIA and a patient who died after experiencing severe ARIA; 8.7% of patients had infusion-related reactions, most of which were mild to moderate.

Copyright © 2023 PHARMCUBE. All Rights Reserved.

Welcome to forward, share, and reasonably cite. When citing, please clearly indicate the source of the article; if you need to reprint, please leave a message to the WeChat Official Account backend or send a message, and specify the name and ID of the official account.

Disclaimer: The information in this WeChat article is for general reference only and should not be directly used as decision-making content. PharmaCube assumes no responsibility for any loss incurred by any party due to the use of the content herein.

PharmaCube Reader Survey Questionnaire

Thank you for your companionship. Looking forward to your feedback.

Scan the QR code to provide valuable suggestions