Eli Lilly and company announced this week that its Alzheimer’s drug candidate, donanemab, glowed in phase 3 trials, meeting all its primary and secondary endpoints.
TRAILBLAZER-ALZ 2 is a randomized double-blind, placebo-controlled study that evaluated the safety and efficacy of the investigational amyloid plaque targeting therapy. The study included 1736 patients in early stages of Alzheimer's disease — presenting mild cognitive impairment and mild dementia — and who had confirmed AD neuropathology. Participants were then divided into cohorts based on their levels of tau protein in the brain, a predictive biomarker for Alzheimer's disease progression.
Results showed that donanemab slowed cognitive and functional decline, with a 35% reduction in decline as measured by the integrated Alzheimer's Disease Rating Scale (iADRS) and a 36% reduction as measured by Clinical Dementia Rating-Sum of Boxes, or CDR-SB (CDR-SB) over 18 months. Additional analyses showed that participants on donanemab had a lower risk of progressing to the next stage of the disease and a decreased decline in the ability to perform daily activities.
While donanemab outperformed Eisai and Biogen’s Leqembi — which slowed down cognitive decline by 27% — donanemab had a greater incidence of ARIA, a known side effect of the class of drugs that lower amyloid levels. In donanemab’s confirmatory trial, 1.6% of participants experienced serious ARIA, which included three deaths. Leqembi was approved under an accelerated approval pathway earlier this year and is still awaiting an FDA decision on full approval.
Earlier this year, the FDA rejected Lilly’s bid for accelerated approval of donanemab. In the CRL, the agency specifically requested that Lilly provide data from at least 100 patients who received a minimum of 12 months of continued treatment on donanemab.
Now, with confirmatory data in hand, Lilly is planning to proceed with global regulatory submissions and expects to submit the drug to the FDA for traditional approval this quarter.
