May 4, 2023 – Investigational drug donanemab significantly slowed the decline in Alzheimer's patients' ability to think clearly and perform each day tasks in a big study of adults with early signs of the disease, in response to initial results.
Donanemab – which is made by Eli Lily and targets amyloid plaques, a trademark of Alzheimer's disease – met the study's primary and secondary objectives related to measures of cognitive and functional decline and demonstrated “significant clinical benefits,” the drugmaker said in a news release.
Based on the outcomes, Lilly plans to ask the FDA for approval of the drug by the tip of June.
In the randomized, double-blind, placebo-controlled study, almost half (47%) of patients taking donanemab experienced no clinical progression after one 12 months, compared with 29% of patients taking placebo.
In addition, compared with placebo, donanemab slowed clinical decline by 35% and resulted in a 40% smaller decline in the power to perform each day activities.
Patients taking donanemab had a 39% lower risk of progressing to the following stage of the disease in comparison with those taking placebo.
In addition to slowing cognitive and functional decline, donanemab resulted in a big reduction in amyloid plaque concentration within the brain as early as six months after starting treatment.
As a results of achieving a certain level of amyloid plaque clearance, 52% of study participants accomplished their treatment after one 12 months and 72% after 18 months, Eli Lilly said..
“These are the strongest Phase 3 data to date for an Alzheimer's treatment,” said Dr. Maria C. Carrillo, chief scientific officer of the Alzheimer's Association, in a press release.
The people examined within the study were divided into groups in response to their tau levels. Tau is a predictive biomarker for the progression of Alzheimer's disease. The primary evaluation population of 1,182 patients consisted of individuals with an intermediate tau level and clinical symptoms of Alzheimer's disease.
The study also included 552 individuals who had high tau levels in the beginning of the study, which corresponds to a later stage of the disease.
In an evaluation of 1,736 participants with high and moderate tau levels, donanemab also showed “significant positive” results across all clinical goals, Eli Lilly said.
However, there have been some unintended effects consistent with earlier phases of research, corresponding to brain swelling and small brain bleeds often known as amyloid-related imaging abnormalities, or ARIA. Three deaths were attributed to various degrees of disease severity.
In the general donanemab-treated group, 24% of subjects experienced brain swelling, with 6% having symptomatic abnormalities.
The small brain hemorrhages occurred in about 31% of patients within the donanemab group and in about 14% within the placebo group. Most cases of the disease were mild to moderate and healed or stabilized with appropriate treatment.
“Encouraging” results, full data eagerly awaited
In a press release from the British nonprofit Science Media Center, Paresh Malhotra, PhD, professor of clinical neurology at Imperial College London, said these latest findings “provide further evidence that antibody treatments that reduce amyloid in the brain can slow the decline in thinking and the ability to perform everyday activities in people with early-stage Alzheimer's disease.”
“These are really encouraging results and show that targeting fundamental mechanisms of Alzheimer's disease can potentially make a difference in people's lives,” he said.
Catherine Mummery, MD, PhD of University College London Hospitals NHS Foundation Trust also commented, saying the outcomes confirmed that “we are now entering the era of treating Alzheimer’s disease.”
“After many years of negative studies, we now have consistent results from several anti-amyloid antibodies showing that removing amyloid alters the course of the disease,” she said..
Mummery also identified that the tactic of administering the drug could reduce the burden and price of treatment.
“This drug was only given until the amyloid levels were reduced to a low enough level and then stopped – which was 52% after 12 months and 72% after 18 months. This could be a way to induce 'remission' in Alzheimer's and then continue to monitor without treatment,” she said.
Liz Coulthard, PhD, associate professor of dementia neurology on the University of Bristol, was more cautious concerning the findings. “At first glance, these data look positive, but we need to see the entire data set,” she said.
“There are significant side effects and we need to know more about how these have affected people. We also need to know the longer-term effects of donanemab,” she said.
Further data from the study can be presented on the Alzheimer's Association's international conference in July..