Alzheimer’s drug donanemab shows strongest Phase III trial data to date
An experimental Alzheimer’s drug, called donanemab, has significantly slowed cognitive and functional decline in a Phase III trial in people with early symptomatic Alzheimer’s disease.
The past couple of years have been positive for Alzheimer’s therapeutics – after nearly 20 years without an Alzheimer’s drug approval, the US FDA approved aducanumab in 2021 and lecanemab in early 2023. This list could soon grow, as Eli Lilly (IN, USA) announced positive results for the Phase III trial of their Alzheimer’s drug donanemab. Donanemab is a monoclonal antibody, like aducanumab and lecanemab, that targets abnormal amyloid-β peptide in the brain.
The trial, called TRAILBLAZER-ALZ 2, saw 1736 people with early symptomatic Alzheimer’s disease randomized to receive either donanemab or a placebo. Donanemab slowed cognitive decline by 35%, as measured on the integrated Alzheimer’s Disease Rating Scale (iADRS), compared to placebo over 18 months. When measured using the Clinical Dementia Rating-Sum of Boxes (CDR-SB) scale, it slowed cognitive decline by 36%. These are the strongest Phase III trial data we have seen to date – to compare, lecanemab slowed cognitive decline by 27% after 18 months (measured with the CDR-SB scale).
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. Eli Lilly noted that the incidence of serious ARIA was 1.6%, including two participants whose death was attributed to ARIA and a third participant who died after an incident of serious ARIA.
Based on these results, Eli Lilly will proceed with global regulatory submissions, including submitting to the US FDA by the end of June.
Talking to the Science Media Centre (London, UK), Nick Fox, Professor of Neurology and Group Leader at the UK Dementia Research Institute, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust (all London, UK) commented, “Although we only have a press release, this announcement is consistent with earlier phase 2 results – and confirms that we are in a new era of disease modification for Alzheimer’s disease. Dramatic and rapid amyloid removal was accompanied by slowing of cognitive decline. The challenge now is to be able to deliver these therapies in already stretched health care systems and to do so safely.”
The full data is expected to be released at the Alzheimer’s Association International Conference (AAIC; Amsterdam, Netherlands) in July 2023.
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