Emerging evidence from an unpublished, non-peer-reviewed study reveals that a new drug candidate from manufacturer Eli Lilly – donanemab – has shown promising positive results on slowing cognitive decline in a small phase II study. By targeting a modified form of the beta-amyloid known as N3pG, the investigated agent appears to slow down decline in patients with early symptoms of Alzheimer’s disease, according to Eli Lilly.
Examining the Efficacy of Donanemab
As part of the phase II TRAILBLAZER-ALZ study, the trial enrolled 272 patients with early asymptomatic Alzheimer’s disease who were selected based on cognitive assessments and imaging data. The TRAILBLAZER-ALZ trial is a randomized, placebo-controlled, double-blind, multi-center phase 2 study of the safety, tolerability, and efficacy of donanemab in patients with early symptoms of AD.
The primary endpoint measured was the change from baseline until 76 weeks in the Integrated Alzheimer’s Disease Rating Scale (iADRS), which is a composite tool combining scores from the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and the Alzheimer’s Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-iADL).
Slower Decline in Early AD
The team of researchers found that donanemab treatment showed significant slowing of declines in a composite measure of cognition and daily function versus placebo. On average, the drug was able to slow decline by 32% relative to placebo, reducing amyloid plaque by 84 centiloid by 72 weeks, compared with baseline levels of 108 centiloids. Study participants ceased donanemab treatment once their plaque levels were below 25 centiloids for two consecutive measurements or below 11 centiloids at one measure.
“This unique mechanism and antibody for clearing plaques, discovered at Lilly, has the potential to provide high levels of durable amyloid plaque clearance after limited duration dosing,” chief science officer Daniel Skovronsky, MD, Ph.D., president of Lilly Research Laboratories, explained in a press release.
In addition, the safety of donanemab was consistent with the drug’s profile from phase I studies. Amyloid-related imaging abnormalities (ARIA) were observed; ARIA-edema was found in 27% of treated patients with an overall incidence of 6% presenting with symptomatic ARIA-E.
The latest findings support the promising potential of donanemab therapy for the early treatment of Alzheimer’s disease which could have significant implications for healthcare, public health, and socioeconomic expenditure.
“In conjunction with our expertise in amyloid and tau imaging, this allowed us to conduct a trial to test if reducing amyloid plaques in Alzheimer’s patients to levels seen in scans of healthy individuals could result in clinically meaningful slowing of cognitive decline,” Skovronsky said. “The positive results we have obtained today give us confidence in donanemab and support its rapid and deep plaque clearance for the potential treatment of Alzheimer’s disease.”
The full results of the ongoing phase II TRAILBLAZER-ALZ 2 study, which continues to examine the safety, tolerability, and efficacy of donanemab, will be made available in the near future and submitted for peer-review.
