Donanemab slows cognitive decline by 60% in people with early Alzheimer’s disease

The results of a Phase 3 trial show that Eli Lilly’s Alzheimer’s drug, donanemab, can significantly slow down functional decline.

The trial found that younger patients and those in the earlier stages of Alzheimer’s disease had the greatest benefits.

In participants with mild cognitive impairment, donanemab slowed decline by 60% on the Integrated Alzheimer’s Disease Rating Scale (iADRS) and 46% on the Clinical Dementia Rating (CDR) scale.

In participants under the age of 75, donanemab slowed decline by 48% on iADRS and 45% on CDR-SB, compared to 25% on iADRS and 29% on CDR-SB in those over that age of 75.

Furthermore, nearly half of participants at an earlier stage of the disease on donanemab had no clinical progression at one year.

The results of the trial revealed that treatment effect continued to increase relative to placebo over the course of the trial, even though many participants completed their course of therapy at six or 12 months, supporting limited duration dosing.

Liana Apostolova, professor in Alzheimer’s Disease research and professor in neurology, radiology, medical and molecular genetic, said: “These results demonstrate that diagnosing and treating people earlier in the course of Alzheimer’s disease may lead to greater clinical benefit.

“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.”

A quarter of those on donanemab experienced side effects

The results of the TRAILBLAZER-ALZ 2 trial, which included nearly 1,800 people with early Alzheimer’s disease, were presented at the Alzheimer’s Association International Conference in Amsterdam.

The results also reveal more about donanemab’s safety profile. During the trial, roughly a quarter (24%) of those receiving the drug experienced side effects (including brain swelling and infusion-related reactions). Four deaths were also recorded as a result of the drug.

Alzheimer’s Research UK’s Executive Director of Research & Partnerships, Dr Susan Kohlhaas says regulators will now need to “balance these benefits and risks before it is given a license for use.”

Alzheimer’s Research UK has now written to Eli Lilly calling on them to put donanemab forward for regulatory review in the UK without delay. “We believe this review should be conducted by the UK regulators as a priority,” said Dr Kohlhaas.

Treatment course could be as short as six months

Despite the risks, the drug’s manufacturer says this new data should “bring hope to people with Alzheimer’s disease who urgently need new treatment options.”

A spokesperson said: “This is the first Phase 3 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.

“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. 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.”