New Data for Alzheimer Agent Presented at International Conference

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Results from the phase 2 TRAILBLAZER-ALZ were presented at the 15th International Conference on Alzheimer & Parkinson DiseasesTM 2021.¹ The new data expanded on earlier top-line data for donanemab, and was also published in the New England Journal of Medicine.² Not only did donanemab meet its primary endpoint, but it also showed significant slowing of decline on the integrated Alzheimer Disease Rating Scale (iADRS) in participants with early Alzheimer disease when compared to placebo.

“We are confident in the results of the TRAILBLAZER-ALZ study,” Daniel Skovronsky, MD, PhD, Eli Lilly and Company’s chief scientific officer and president of Lilly Research Laboratories, said to the press. “This is the first late-stage study in Alzheimer disease to meet its primary endpoint at the primary analysis. Donanemab has the potential to become a very important treatment for Alzheimer disease.”¹

Donanemab, a monoclonal antibody, was designed to target a particular form of post-translationally modified Aß, N-terminal pyroglutamate, and completely clear amyloid plaques.

Secondary analyses showed donanemab consistently slowed cognitive and functional decline, with ranges between 20% to 40% in all secondary endpoints. Analyses also showed donanemab slowed the accumulation of tau across important brain regions in participants with Alzheimer disease. 

“We were pleased to see not only slowing of cognitive and functional decline, but also very substantial clearance of amyloid plaques and slowing of spread of tau pathology,” Skovronsky further noted. “The constellation of clinical and biomarker results indicates the potential for long-term disease modification. We are grateful to the patients, caregivers, and investigators who participated in this landmark study.”

Treatment with donanemab slowed decline by 32% when compared to placebo, measured by the iADRS, at 76 weeks compared to baseline. This was statistically significant. Noticeable difference in decline was observed as early as 36 weeks after initiation of treatment. About 40% of participants achieved amyloid negativity after treatment with donanemab as early as 6 months into treatment, and 68% achieved negativity by 18 months into treatment.

“Tau has become increasingly validated as a predictive biomarker for Alzheimer's disease progression, as shown again in this trial,” said Liana G. Apostolova, MD, MSc, FAAN, Indiana University (IU) Distinguished Professor and Barbara and Peer Baekgaard Professor in Alzheimer Disease Research at IU School of Medicine. “A key insight of the results from the TRAILBLAZER-ALZ study is that donanemab not only significantly reduced the amount of amyloid deposition in these patients but also slowed the clinical progression of the disease suggesting that this could be a disease-modifying therapy. We believe these amyloid and tau imaging data lay the foundation for precision medicine-based Alzheimer disease treatments.”

Stephen P. Salloway, MS, MD, Director of the Memory and Aging Program and the Department of Neurology at Butler Hospital, Martin M. Zucker professor of Psychiatry and Human Behavior at Warren Alpert Medical School of Brown University, added: “As a clinician and researcher, I’m particularly encouraged by the significant plaque lowering and the slowing of clinical decline with donanemab. The donanemab results are a significant and encouraging milestone for people impacted by Alzheimer disease and we are eager to continue on in this fight.”

References

1. Eli Lilly and Company. Lilly's donanemab slowed Alzheimer’s disease progression in Phase 2 trial: full data presented at AD/PD™ 2021 and published in NEJM. PR Newswire. March 13, 2021. https://www.prnewswire.com/news-releases/lillys-donanemab-slowed-alzheimers-disease-progression-in-phase-2-trial-full-data-presented-at-adpd-2021-and-published-in-nejm-301246745.html

2. Mintun MA, Lo AC, Evans CD, et al. Donanemab in early Alzheimer’s disease. NEJM. March 13, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2100708