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Lucy Chard
18 Jul 2023

Alzheimer's drug donanemab deemed effective in landmark clinical trial

Results from the TRAILBLAZER-ALZ 2 Randomised Clinical Trial into the use of donanemab to treat early symptoms of Alzheimer’s disease have been analysed. 

The Phase III trial included 1736 participants who demonstrated symptoms of the early stages of Alzheimer’s disease, in the form of amyloid plaques and tau pathology. The results of the trial, published in JAMA, showed that donanemab significantly slows the cognitive and functional decline in these patients. 

"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," explained Anne White, Executive Vice President of Eli Lilly and Company, and President of Lilly Neuroscience. "If approved, we believe donanemab can provide clinically meaningful benefits for people with this disease and the possibility of completing their course of treatment as early as 6 months once their amyloid plaque is cleared. We must continue to remove any barriers in access to amyloid-targeting therapies and diagnostics in an already complex healthcare ecosystem for Alzheimer's disease."

Previous announcements from Eli Lilly stated that donanemab had met all the primary and secondary endpoints laid out in the study, and based off of this, applied for US FDA approval to treat those with mild cognitive impairment or mild dementia, with approval applications to other global bodies currently in process. 

In the 18-month trial, participants were split into groups according to their exhibited symptoms, a low/medium tau (68.1%) or high tau pathology (31.8%), which was determined using PET imaging from June 2020 to November 2021. Of those taking part initially, 1320 completed the trial. 

The results showed that, out of the 24 outcomes measured and analysed, 23 were statistically significant and overall it was concluded that donanemab, when compared to placebo, slowed clinical progression in both groups of participants, at 76 weeks, according to the integrated Alzheimer's Disease Rating Scale (iADRS) and the Clinical Dementia Rating-Sum of Boxes (CDR-SB). 

"These results demonstrate that diagnosing and treating people earlier in the course of Alzheimer's disease may lead to greater clinical benefit," added Liana Apostolova, a Professor in Alzheimer's disease research and Professor in neurology, radiology, medical and molecular genetics at Indiana University School of Medicine, where she is Associate Dean for Alzheimer's disease research and directs the clinical core of the Alzheimer's Disease Centre. "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."

Donanemab is a monoclonal antibody that specifically singles out the deposits of amyloid plaque in the brain, and leads to clearance of the plaques. Without the plaques hindering normal brain function, patients can have a greater chance of living out a fuller life for longer. 

The number of adverse events that occurred in patients throughout the trial were consistent with previous Alzheimer’s studies. This took the form of ARIA, which is expected with antibody-based therapies of this kind. The ARIAs can be detected via MRI scans, and treated as necessary. 

"People living with early, symptomatic Alzheimer's disease are still working, enjoying trips, sharing quality time with family – they want to feel like themselves, for longer," commented Mark Mintun, Group Vice President of Neuroscience Research & Development at Lilly, and President of Avid Radiopharmaceuticals. "The results of this study reinforce the importance of diagnosing and treating disease sooner than we do today."

Source: Lilly. Results from Lilly's Landmark Phase 3 Trial of Donanemab Presented at Alzheimer's Association Conference and Published in JAMA. [Date accessed 18/07/2023]

Lucy Chard
Digital Editor - Pharma

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