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Eli Lilly announces positive top results from Phase II study of donanemab in Alzheimer’s disease

Monday 11 January 2021

On 11 January, the pharmaceutical company Eli Lilly announced that its Phase II clinical trial evaluating donanemab in Alzheimer’s disease (AD) met its primary endpoint. Donanemab is an investigational antiamyloid therapy, targeting a modified form of beta amyloid called N3pG. The Phase 2 TRAILBLAZER-ALZ trial was a randomised, placebo-controlled, double-blind and multi-center study evaluating the safety, tolerability and efficacy of donanemab in people with early symptomatic AD.  The study enrolled 272 participants from Canada and US based on cognitive assessments, amyloid plaque imaging, and tau imaging.

The study reported that donanemab showed a significantly slower decline in cognition and daily function compared to placebo. Donanemab met the primary endpoint of change from baseline to 76 weeks in the Integrated AD Rating Scale (iADRS), slowing decline by 32% relative to placebo. The iADRS is a clinical composite tool combining the cognitive measure ADAS-Cog13 and functional measure ADCS-iADL, two measures used in AD.

Donanemab also showed consistent improvements in secondary endpoints measuring cognition and function as compared to placebo, but not all of these secondary endpoints reached statistical significance. Key secondary endpoints include changes between baseline and 76 weeks in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13), ADCS-iADL, MMSE, and Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores. Biomarkers such as amyloid and tau deposition in the brain were also assessed as secondary outcomes at week 76. In TRAILBLAZER-ALZ, donanemab showed a reduction of amyloid plaques with an average of 78%, or an 84 centiloid reduction at 76 weeks compared to a baseline of 108 centiloids. The company added that the safety of donanemab was acceptable and consistent with observations from Phase I data. In the donanemab treatment group, amyloid-related imaging abnormalities – edema (ARIA-E) occurred in 27% of treated participants, with an overall incidence of 6% experiencing symptomatic ARIA-E.

Patients assessed in TRAIBLAZER-ALZ are still participating in the ongoing follow-up trial TRAILBLAZER-EXT. The company plans to present the full results of TRAILBLAZER-ALZ at an upcoming conference. In addition, a second Phase II trial TRAILBLAZER-ALZ 2 is evaluating the safety, tolerability and efficacy of donanemab in people with early AD. The TRAILBLAZER-ALZ 2 was initiated in June 2020.