Donanemab marks start of “new story” in Alzheimer’s research

Professor Craig Ritchie has told an international Alzheimer’s conference that phase 3 clinical trial results for donanemab, the antibody drug designed to target and clear the amyloid plaques considered key to progression of Alzheimer’s disease, reveal the drug’s “profound” clinical effect.

Results published in the JAMA Neurology paper show the positive effects of the drug among patients with early-stage Alzheimer’s disease, slowing both cognitive and functional decline.

This phase 3 randomised trial of early symptomatic Alzheimer’s disease participants with amyloid plaques and tau tangles – known as TRAILBLAZER ALZ-2 – found that donanemab treatment slowed disease progression by up to 35.1%.

Professor Craig Ritchie, CEO of Scottish Brain Sciences and a co-author of the landmark paper said:

“These data give final confirmation that we have entered a new, overdue and exciting chapter in the battle against Alzheimer’s disease.

“Now is the time to once and for all recognise that Alzheimer’s disease is a brain disease with cognitive symptoms and not the 20th century view of it being a (dementia) syndrome only defined by cognitive and functional impairment.

“Donanemab had a profound effect on the core pathology of Alzheimer’s disease namely cerebral amyloid, and this led to truly meaningful and observable clinical benefit.

“We know these diseases start decades before symptoms emerge and through work here in Scotland by Brain Health Scotland, we are nationally very well positioned to detect the earliest stages of these brain diseases well before symptoms emerge. There is a lot more to come in the years ahead and that will be positive if we all embrace the new narrative of this chapter.”

Professor Ritchie shared key findings at the Alzheimer’s Association International Conference being held in Amsterdam across the 16^th to the 20^th of July.

This drug tackles the amyloid plaques which have been found to build in patients with Alzheimer’s disease, while other proteins called tau tangles, have also been identified as a defining feature of Alzheimer’s – contributing to a decline in brain function.

However, some researchers have highlighted the importance of addressing other aspects of Alzheimer’s disease beyond these protein build-ups, while others have expressed concern about the safety of donanemab.

The paper reported that, while, in a small number of people, serious side effects were observed for both the donanemab and placebo group, the drug ‘significantly slowed’ clinical progression of Alzheimer’s disease.

Researchers highlight the importance of further evaluation of the risk and long-term impact of donanemab to maximise its potential benefits for Alzheimer’s patients.

Speaking to the International broadcaster Al Jazeera during the conference, Professor Ritchie explained that findings provide hope for the future of Alzheimer’s disease treatment:

“I think these drugs give us hope that we can do something – these are the first drugs of a new generation. They are not the not the end of the story, they’re the beginning of a new story.

Professor Ritchie continued, highlighting that concerns around safety and monitoring risks will be part of this future:

“Sure there are safety concerns, there are safety concerns with any drugs – the thing is we know what those safety concerns are… it’s something we can monitor.”

The pharmaceutical company behind the trial, Eli Lilly, has already completed submission to the US Food and Drug Administration and is expecting a response by the end of 2023. Submissions to other global regulators are currently underway.

Anne White, Executive Vice-President of Eli Lilly and Company and president of Lilly Neuroscience, said:

“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 six months once their amyloid plaque is cleared.”