Lilly's donanemab slowed Alzheimer's disease progression in Phase 2 trial: full data presented at AD/PD™ 2021 and published in NEJM
Additionally, data from secondary analyses showed donanemab consistently slowed cognitive and functional decline, with ranges between 20-40 percent in all secondary endpoints [Clinical Dementia Rating Scale Sum of Boxes (CDR-SB), Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog13), Alzheimer's Disease Cooperative Study-instrumental Activities of Daily Living (ADCS-iADL), Mini-Mental State Examination (MMSE)] with nominal statistical significance at multiple times compared to placebo. Further, prespecified exploratory analyses showed donanemab slowed the accumulation of tau across key brain regions in patients affected by Alzheimer's disease.
"We are confident in the results of the TRAILBLAZER-ALZ study," said
Specifically, at 76 weeks compared to baseline, treatment with donanemab slowed decline by 32 percent compared to placebo as measured by the iADRS, which was statistically significant. As early as nine months (36 weeks) after initiation of treatment, a significant difference in decline by iADRS was observed.
In addition, 40 percent of participants treated with donanemab achieved amyloid negativity as early as six months after starting treatment and 68 percent achieved this target by 18 months. Donanemab is a monoclonal antibody that was designed to bind a specific form of post-translationally modified Aß, N-terminal pyroglutamate, and thereby yield rapid and complete clearance of amyloid plaques.
"Tau has become increasingly validated as a predictive biomarker for Alzheimer's disease progression, as shown again in this trial," said
The safety profile of donanemab was consistent with observations from Phase 1 data. In the donanemab treatment group, amyloid-related imaging abnormalities – edema (ARIA-E) occurred in 26.7 percent of treated participants, with an overall incidence of 6.1 percent experiencing symptomatic ARIA-E; the majority ARIA-E cases occurred within the first 12 weeks after initiation of treatment. Other common AEs in the donanemab treatment group include ARIA-H related events like microhemorrhages (7.6 percent) and superficial siderosis of central nervous system (13.7 percent), nausea (10.7 percent), and infusion-related reaction (IRR) (7.6 percent). Serious IRR or hypersensitivity occurred in 2.3 percent of participants treated with donanemab. In the donanemab arm, 30.5 percent of patients discontinued treatment due to an adverse event and half of these discontinuations were due to ARIA-related events. Patients with treatment discontinuations were allowed to continue in the trial.
"As a clinician and researcher, I'm particularly encouraged by the significant plaque lowering and the slowing of clinical decline with donanemab," said
Discussions with regulators are ongoing and an update on the TRAILBLAZER clinical trial program will be provided on a webcast on
About TRAILBLAZER-ALZ Study
TRAILBLAZER-ALZ (NCT03367403) is a randomized, placebo-controlled, double-blind, multi-center Phase 2 study to assess the safety, tolerability and efficacy of donanemab in patients with early symptomatic Alzheimer's disease. The trial enrolled 272 patients who were selected based on cognitive assessments in conjunction with amyloid plaque imaging and tau staging by PET imaging. The study's primary endpoint is change from baseline until 76 weeks in the Integrated Alzheimer's Disease Rating Scale (iADRS), a composite tool combining the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog13) and the Alzheimer's Disease Cooperative Study - instrumental Activities of Daily Living (ADCS-iADL) for function. Key secondary endpoints include changes between baseline and 76 weeks in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13), ADCS-iADL, MMSE, and Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores. Other secondary biomarker endpoints include changes from baseline to week 76 in brain amyloid deposition and brain tau deposition and volumetric MRI. The safety, tolerability and efficacy of donanemab are also being evaluated in the ongoing randomized, placebo-controlled, double-blind, multi-center Phase 2 study TRAILBLAZER-ALZ 2 (NCT04437511).
About Alzheimer's Disease
Alzheimer's disease is a fatal illness that causes progressive decline in memory and other aspects of cognition. Dementia due to Alzheimer's disease is the most common form of dementia, accounting for 60 to 80 percent of all cases3. There are currently over 50 million people living with dementia around the world, with numbers expected to increase to nearly 152 million by 20504. Almost 10 million new cases of dementia are diagnosed each year worldwide, implying one new case every 3 seconds, and a significant increase in the caregiving burden placed on society and families. In the US alone, there was an increase of 8 million new caregivers from 2015 to 20205. The current annual societal and economic cost of dementia is estimated at
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about
- Mintun M, Lo AC, et. al. Donanemab Slows Progression of Early Symptomatic Alzheimer's Disease in Phase 2 Proof of Concept Trial. Presented virtually at the International Conference on Alzheimer's & Parkinson Diseases™ 2021 (AD/PD™ 2021);
- Mintun M, Lo AC, et. al. (2021). Donanemab in Early Alzheimer's Disease.
New England Journal of Medicine, https://www.nejm.org/doi/full/10.1056/NEJMoa2100708. Alzheimer's Association. Facts and Figures. https://www.alz.org/alzheimers-dementia/facts-figures. Accessed December 8, 2020. Alzheimer's Disease International. World Alzheimer Report 2019. https://www.alz.co.uk/research/WorldAlzheimerReport2019.pdf. Accessed December 8, 2020. AARP. 2020 Report: Caregiving in the U.S.https://www.aarp.org/content/dam/aarp/ppi/2020/05/full-report-caregiving-in-the-united-states.doi.10.26419-2Fppi.00103.001.pdf. Accessed December 8, 2020.
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