In the late-stage trial, the investigational amyloid plaque targeting therapy significantly decelerated cognitive and functional decline in patients with early symptomatic Alzheimer's disease
Donanemab is an investigational amyloid plaque-targeting therapy. (Credit: Robina Weermeijer on Unsplash)
Eli Lilly and Company (Lilly) said that donanemab has met the primary endpoint and all secondary endpoints in the TRAILBLAZER-ALZ 2 phase 3 trial in Alzheimer’s disease (AD).
The investigational amyloid plaque targeting therapy significantly decelerated cognitive and functional decline in people with early symptomatic Alzheimer’s disease in the late-stage trial.
TRAILBLAZER-ALZ 2 is a randomised, double-blind, placebo-controlled trial. Its objective is to assess the safety and efficacy of donanemab.
The late-stage trial recruited patients with early symptomatic Alzheimer’s disease, This included those with mild cognitive impairment (MCI) and the disease’s mild dementia stage, with confirmed presence of Alzheimer’s disease neuropathology.
Under the trial, patients completed their treatment course with donanemab after they reached a prespecified level of clearance of amyloid plaque.
The primary endpoint of the phase 3 clinical trial was variation from baseline until 18 months on the integrated Alzheimer’s Disease Rating Scale (iADRS).
According to Lilly, iADRS measures daily life activities and cognition like finance management, driving, engagement in hobbies, as well as discussing current events.
The secondary endpoints included cognitive and functional decline and the drug candidate delivered highly statistically substantial clinical benefits with similar magnitude.
In the primary analysis population, the primary endpoint of iADRS demonstrated a 35% slowing of decline and the key secondary endpoint of Clinical Dementia Rating-Sum of Boxes (CDR-SB) indicated a 36% slowing of decline over 18 months.
Furthermore, the additional prespecified secondary analysis showed that 47% of the patients on donanemab showed no decline in CDR-SB at one year.
Additionally, the TRAILBLAZER-ALZ 2 trial revealed that participants dosed with donanemab had a 40% less decline in the ability to undertake activities of daily living at 18 months. The patients also had a 39% lower risk of progressing to the next stage of disease compared to placebo.
Lilly chief scientific and medical officer and Lilly Research Laboratories president Daniel Skovronsky said: “We are extremely pleased that donanemab yielded positive clinical results with compelling statistical significance for people with Alzheimer’s disease in this trial.
“This is the first Phase 3 trial of any investigational medicine for Alzheimer’s disease to deliver 35% slowing of clinical and functional decline.”
Based on the TRAILBLAZER-ALZ 2 trial results, the pharmaceutical major is planning to proceed with global regulatory submissions. It is expected to make a submission to the US Food and Drug Administration (FDA) during this quarter.
Donanemab secured breakthrough therapy designation from the FDA in June 2021.