Donanemab slows the progression of Alzheimer’s symptoms by a third

A new dementia drug, donanemab, significantly slows cognitive and functional decline in people with early symptomatic Alzheimer’s disease, according to the results of a new study.

It slowed progression of Alzheimer’s by 35% compared to a placebo in 1,182 people with early-stage disease whose brains had deposits of two key Alzheimer’s proteins, beta amyloid as well as intermediate levels of tau, a protein linked with disease progression and brain cell death.

The study also evaluated the drug in 552 patients with high levels of tau and found that when both groups were combined, donanemab slowed progression by 29% based on a commonly used scale of dementia progression known as the Clinical Dementia Rating Scale (CDR-SB).

Findings from the TRAILBLAZER-ALZ 2 study also found that participants on donanemab showed a 40% less decline in their ability to perform activities of daily living at 18 months and experienced a 39% lower risk of progressing to the next stage of disease compared to placebo.

Beginning of the end of Alzheimer’s disease

The Alzheimer’s Society said that together with lecanemab, which made headlines last year as a promising new drug for people living with early-stage Alzheimer’s disease, this could be the beginning of the end of Alzheimer’s disease.

Dr Richard Oakley, Associate Director of Research at Alzheimer’s Society, said: “Based on today’s early results, donanemab appears to slow the progression of Alzheimer’s symptoms by 36 % (as compared with 27% of last year’s breakthrough drug lecanemab). Promisingly, the trial also demonstrated a 40% slowing in decline of everyday activities such as driving, doing hobbies and managing finances.
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“While we’ve seen lecanemab could slow progression by over seven months, we’ll need to see the full results to know if donanemab could do the same or even better. We need decisions as quickly as possible from the regulators MHRA and NICE. But that’s not the end of the story – we can’t end up in a situation where there are new drugs being approved but people can’t get access to them early in their dementia journey when they work best – we need more accurate, earlier dementia diagnosis in the NHS.”

The randomised, double-blind, placebo-controlled study, evaluated the safety and efficacy of donanemab, an investigational amyloid plaque targeting therapy. The study enrolled people with early symptomatic Alzheimer’s disease (AD), which includes mild cognitive impairment (MCI) and the mild dementia stage of disease, with the confirmed presence of AD neuropathology, and participants completed their course of treatment with donanemab once they reached a prespecified level of amyloid plaque clearance.

Participants were stratified by their level of the brain protein tau, a predictive biomarker for Alzheimer’s disease progression. The primary analysis population (n=1182) for which the study was powered was comprised of people with an intermediate level of tau and clinical symptoms of Alzheimer’s disease. In this population, the primary endpoint (iADRS) showed 35% slowing of decline (p<0.0001), and an important key secondary endpoint (Clinical Dementia Rating-Sum of Boxes, or CDR-SB) showed 36% slowing of decline (p<0.0001) over 18 months.

Brain swelling side effects

In the donanemab treatment group, brain swelling, a known side effect of drugs of this type, occurred in 24% of participants, with 6.1% experiencing symptoms. Brain bleeding occurred in 31.4% of the donanemab group and 13.6% of the placebo group.

In the lecanemab Leqembi Phase 3 trial, the drug was associated with brain swelling in nearly 13% of its study participants.

Alzheimer’s Research UK said that these risks of serious side effects need to be fully scrutinised before donanemab can be marketed and used, however the news underlines the urgency of preparing the NHS to make these treatments available should regulators deem them safe and effective.

Dr Susan Kohlhaas, Executive Director of Research & Partnerships, added: “This is incredibly encouraging, and another hugely significant moment for dementia research. A second drug for Alzheimer’s has been shown to slow people’s cognitive decline in a rigorous phase 3 trial.  We’re now on the cusp of a first generation of treatments for Alzheimer’s disease, something that many thought impossible only a decade ago.

“People should be really encouraged by this news, which is yet more proof that research can take us ever closer towards a cure.”

The full details of Eli Lilly’s trial have yet to be published.