July 18, 2023: Eli Lilly’s Alzheimer’s experimental drug, donanedab, slowed down cognitive and functional decline in people with early symptoms of the disease, according to a company statement.
Donanemab significantly slowed the decline for amyloid-positive early symptomatic Alzheimer’s disease patients, lowering their risk of disease progression.
About half of the participants at an earlier stage of the disease and tested with donanemab had no clinical progression at a year.
Further analyses showed that those study participants at the earliest stage of the disease had greater benefits — with a 60% slowing of decline compared to a placebo.
The 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 a year, supporting limited duration dosing during the trial.
“This is the first phase III 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.”
The data were shared at the 2023 Alzheimer’s Association International Conference and published in the Journal of the American Medical Association (JAMA).
The results support Lilly’s application for regulatory approval to treat people with amyloid-positive early symptomatic Alzheimer’s disease (either mild cognitive impairment or mild dementia), regardless of their baseline level of tau, another protein.
The study enrolled participants with a broader range of cognitive scores and amyloid levels than in other recent trials of amyloid plaque-targeting therapies.
Participants were stratified by their tau level, a predictive biomarker for disease progression, into either a low-medium tau group or a high tau group, representing a later pathological stage of disease progression.
All participants were then assessed over 18 months using cognition and function scales. The overall treatment effect of donanemab continued to grow throughout the trial, with the largest differences versus placebo seen at 18 months.
Donanemab targets deposited amyloid plaque and has been shown to lead to plaque clearance in treated patients. Treatment with donanemab significantly reduced amyloid plaque levels regardless of the baseline pathological stage of the disease.
Among all participants, treatment with donanemab reduced amyloid plaque on average by 84% at 18 months, compared with a 1% decrease for participants on placebo. Participants were able to stop taking donanemab once they achieved pre-defined criteria of amyloid plaque clearance.
About half of participants met this threshold at 12 months and approximately seven of every ten participants reached it at 18 months.
Disease progression delay
“These results demonstrate that diagnosing and treating people earlier in the course of Alzheimer’s disease may lead to greater clinical benefit,” said Liana Apostolova, professor in Alzheimer’s Disease research and Professor of neurology, radiology, medical and molecular genetics at Indiana University School of Medicine.
”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.”
Eli Lilly had previously announced that donanemab met the primary and all cognitive and functional secondary endpoints in the phase III study.
Submission to the US FDA for traditional approval was completed last quarter with regulatory action expected by the end of the year.
Other global regulators’ submissions are currently underway, and the majority will be completed by year-end.
Mark Mintun, M.D., group vice president of Neuroscience Research & Development at Lilly said: “The results of this study reinforce the importance of diagnosing and treating disease sooner than we do today.”
According to the statement, the incidence of amyloid-related imaging abnormalities and infusion-related reactions was consistent with the previous study.
The imaging-related abnormalities occur across the class of amyloid plaque-clearing antibody therapies. It is most commonly observed as temporary swelling in an area or areas of the brain or as micro-hemorrhages or superficial siderosis.
These are detected by MRI and may be serious and even fatal in some cases.
This risk should be managed with careful observation, monitoring with MRIs, and appropriate actions if abnormalities are detected. Serious infusion-related reactions and anaphylaxis were also observed.