Novel Alzheimer’s drug donanemab displays positive results in full Phase III trial data
Donanemab significantly slowed cognitive and functional decline for people with early symptomatic Alzheimer’s disease, as revealed by the full Phase III trial data.
Early positive results from the Phase III trial investigating donanemab were previously announced by Eli Lilly and Company (IN, USA), showing promising potential as a new drug to treat Alzheimer’s disease. They announced that donanemab met the primary and all cognitive and functional secondary endpoints, slowing decline by 35% compared to placebo over 18 months. The full trial data has now been released, supporting significantly slowed cognitive and functional decline in people with amyloid-positive early symptomatic Alzheimer’s disease, reducing their risk of disease progression. In addition, this effect was evident regardless of baseline clinical or pathological stage of disease. The results were shared at the 2023 Alzheimer’s Association International Conference (AAIC; 16–20 July 2023, Amsterdam, Netherlands) and published in the Journal of the American Medical Association.
The placebo-controlled trial, named TRAILBLAZER-ALZ 2, evaluated the efficacy and safety of donanemab in 1736 participants, over a period of 18 months. Participants were classified based on their level of tau (a pathological feature of the disease), which was used to indicate clinical progression, with higher levels reflecting a later stage of disease.
Donanemab was found to target and clear amyloid plaque deposits in treated individuals. On average, amyloid plaque levels were lowered by 84% at 18 months following treatment with the drug, compared with a 1% reduction for participants on placebo. Plaque clearance was observed regardless of baseline pathological stage of disease.
The best outcomes were associated with the earliest stages of disease, with nearly half of participants at earlier stages showing no clinical progression at 1 year on the Clinical Dementia Rating (CDR) assessment, and cognitive decline slowing by 60% compared to placebo. The risk of progressing to the next stage of disease also decreased by 39% in these participants. This delay in clinical progression gave participants an extra 7.5 months before their levels of cognitive and functional decline on CDR-SB matched levels of those on placebo. “These results demonstrate that diagnosing and treating people earlier in the course of Alzheimer’s disease may lead to greater clinical benefit,” stated Liana Apostolova, a professor and associate dean for Alzheimer’s disease research at Indiana University School of Medicine (IN, USA).
“The positive TRAILBLAZER-ALZ 2 data bring hope to people with Alzheimer’s disease who urgently need new treatment options. This is the first Phase III study of a disease-modifying therapy to replicate the positive clinical results observed in a previous study,” said Anne White, executive vice president of Eli Lilly and Company and president of Lilly Neuroscience.
However, the drug is not without safety concerns. As with other amyloid-targeting therapies, amyloid-related imaging abnormalities (ARIA) remains an issue that needs to be monitored. ARIA refers to abnormal differences seen in MRI images of the brain, which can result in mild to severe bleeding or swelling in the brain. ARIA occurred in 37% of the treatment group, compared to 15% of the placebo group, and while most cases were mild to moderate and resolved with management, three deaths were attributed to treatment-related ARIA.
The TRAILBLAZER-ALZ 2 results support Lilly’s application for US FDA approval last quarter, to treat people with amyloid-positive early symptomatic Alzheimer’s disease. A decision regarding regulatory approval is expected by the end of the year.
You might also like: