INDIANAPOLIS, March 13, 2021 / PRNewswire / – Results of Phase 2 TRAILBLAZER-ALZ presented today by Eli Lilly and Company (NYSE: LLY) at the 15th International Conference on Alzheimer’s and Parkinson’s Diseases ™ 2021 (AD / PD ™ 2021) held March 9-14, 2021 and published simultaneously in New England Journal of Medicine (NEJM) extended previously reported first-line data that found that donanemab met its primary endpoint and showed a significant slowdown in the decline of the integrated Alzheimer’s disease assessment scale (iADRS), a measure composed of cognition and daily function in patients with early symptomatic Alzheimer’s disease compared with placebo1.2.
In addition, secondary analysis data showed that donanemab steadily decreased 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 on several occasions compared to placebo. In addition, pre-specified exploratory analyzes showed that donanemab slowed the accumulation of tau in key brain regions in patients affected by Alzheimer’s disease.
“We are confident of the results of the TRAILBLAZER-ALZ study,” he said Daniel Skovronsky, MD, Ph.D., scientific director of Lilly and president of Lilly Research Laboratories. “This is the first final study of Alzheimer’s disease that meets its main endpoint in the main analysis. Donanemab has the potential to become a very important treatment for Alzheimer’s disease. We were pleased see not only the slowdown in cognitive and functional impairment, but also a very significant elimination of amyloid plaques and the slowdown in the spread of tau pathology.The constellation of clinical and biomarker results indicates the potential for disease modification in We thank the patients, caregivers and researchers who took part in this flagship study. “
Specifically, at 76 weeks compared to baseline, donanemab treatment decreased the decrease by 32 percent compared with placebo as measured by iADRS, which was statistically significant. Already at nine months (36 weeks) after the start of treatment, a significant difference in iADRS decrease was observed.
In addition, 40% of donanemab-treated participants achieved amyloid negativity just six months after starting treatment and 68% achieved this goal at 18 months. Donanemab is a monoclonal antibody that was designed to bind a specific form of Aß, post-translational modified N-terminal pyroglutamate and thus produce a complete and rapid clearance of amyloid plaques.
“Tau has been increasingly validated as a predictive biomarker for the progression of Alzheimer’s disease, as shown again in this trial,” he said. Liana G. Apostolova, MD, M.Sc., FAAN, Indiana University (UI) Distinguished Professor of Barbara and Peer Baekgaard in Alzheimer’s Disease Research at the UI School of Medicine. “A key idea of the results of 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 it could it is a disease-modifying therapy. We believe this data from amyloid imaging and tau lay the groundwork for precision treatments based on drugs based on Alzheimer’s disease.
The safety profile of donanemab was consistent with observations from phase 1 data. In the donanemab treatment group, amyloid-related image abnormalities (edema (ARIA-E)) occurred in the 26.7% of participants treated, with an overall incidence of 6.1% experiencing symptomatic ARIA-E; most ARIA-E cases occurred within the first 12 weeks after the start of treatment. Other common EAs in the donanemab treatment group include ARIA-H-related events such as microhemorrhages (7.6%) and superficial central nervous system siderosis (13.7%), nausea (10.7%), and reaction related to the infusion (IRR) (7.6%). Severe IRR or hypersensitivity occurred in 2.3% of donanemab-treated participants. In the donanemab arm, 30.5% of patients discontinued treatment due to an adverse event and half of these were due to ARIA-related events. Patients with treatment interruption were allowed to continue in the trial.
“As a physician and researcher, I am especially encouraged by the significant reduction in plaque and the slowdown in clinical decline with donanemab,” he said. Stephen P. Salloway, EM, MD, Director of the Memory and Aging Program and the Department of Neurology at Butler Hospital and Martin M. Zucker Professor of Psychiatry and Human Behavior, Department of Neurology, Warren Alpert School of Medicine Brown University. “The results of donanemab are a significant and encouraging milestone for people affected by Alzheimer’s disease and we look forward to continuing this fight.”
Discussions with regulators are ongoing and an update to the TRAILBLAZER clinical trial program will be provided in a webcast at Monday, March 15th a 10:30 EDT including an update to the ongoing TRAILBLAZER-ALZ 2 test. For more information about the TRAILBLAZER-ALZ 2 study or to see if it prequalifies, visit www.trailblazer2study.com.
About the TRAILBLAZER-ALZ study
TRAILBLAZER-ALZ (NCT03367403) is a multicenter, randomized, placebo-controlled, double-blind, phase 2 study to evaluate the safety, tolerability, and efficacy of donanemab in patients with early symptomatic Alzheimer’s disease. The trial included 272 patients who were selected based on cognitive assessments in conjunction with amyloid plaque imaging and tau staging using PET imaging. The main objective of the study is to change from baseline to 76 weeks the Integrated Alzheimer’s Disease Assessment Scale (iADRS), a composite tool that combines the Alzheimer’s Assessment Scale. Alzheimer’s disease-cognitive subscale (ADAS-Cog13) and the Cooperative Study of Alzheimer’s disease – Daily Living Instrumental Activities (ADCS-iADL) for function. The main secondary endpoints include changes between baseline and 76 weeks in the scores on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13), ADCS-iADL, MMSE, and Box Sum of the clinical dementia classification scale (CDR-SB). Other final criteria for secondary biomarkers include changes from baseline to week 76 in cerebral amyloid deposition and cerebral tau deposition and volumetric resonance. The safety, tolerability, and efficacy of donanemab are also being evaluated in the ongoing TRAILBLAZER-ALZ 2 (NCT04437511), randomized, placebo-controlled, double-blind, multicenter study.
About Alzheimer’s disease
Alzheimer’s disease is a deadly disease that causes a progressive decrease 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 cases.3. There are currently more than 50 million people living with dementia worldwide, and the numbers are expected to increase to about 152 million by 20504. Nearly 10 million new cases of dementia are diagnosed worldwide each year, implying one new case every 3 seconds and a significant increase in the care burden of society and families. In the United States alone, there was an increase of 8 million new caregivers from 2015 to 20205. It is estimated at the current annual social and economic cost of dementia $ 1 trillion, an amount that is expected to double by 2030 unless we find a way to slow the disease4.
About Eli Lilly and Company
Lilly is a world health leader who combines care with discovery to improve the lives of people around the world. We were founded more than a century ago by a man committed to creating high quality medicines that meet real needs, and today we remain faithful to this mission throughout our work. Around the world, Lilly employees work to discover and bring life-changing drugs to those who need them, improve understanding and management of disease, and return to communities through philanthropy and volunteering. To learn more about Lilly, visit us at lilly.com and lilly.com/newsroom. P-LLY
Lilly’s cautionary statement about future statements
This press release contains forward-looking statements (as defined in the Private Securities Litigation Reform Act of 1995) about the Lilly Alzheimer’s Disease Platform, including donanemab as a potential treatment for people with early symptomatic Alzheimer’s disease and reflects Lilly’s current beliefs and expectations. However, as with any such company, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that the future results of the study will be consistent with the results of the study to date, that donanemab will prove to be a safe and effective treatment, or that donanemab will receive regulatory approval. For more information about these and other risks and uncertainties, see the Lilly’s Form 10-K application and Form 10-Q with the United States Securities and Exchange Commission. Except as required by law, Lilly does not undertake to update the forward-looking statements to reflect events subsequent to the date of this release.
- Mintun M, Lo AC, et. at the. Donanemab slows the progression of early symptomatic Alzheimer’s disease in the Phase 2 concept test. Presented virtually at the International Conference on Alzheimer’s and Parkinson’s Diseases ™ 2021 (AD / PD ™ 2021); March 9-14.
- Mintun M, Lo AC, et. at the. (2021). Donanemab in early Alzheimer’s disease. New England Journal of Medicine, https://www.nejm.org/doi/full/10.1056/NEJMoa2100708.
- Alzheimer’s Association. Data and figures. https://www.alz.org/alzheimers-dementia/facts-figures. It has been accessed December 8, 2020.
- Alzheimer’s Disease International. World Alzheimer’s Report 2019. https://www.alz.co.uk/research/WorldAlzheimerReport2019.pdf. It has been accessed December 8, 2020.
- AARP. 2020 Report: Caregiving in the US https://www.aarp.org/content/dam/aarp/ppi/2020/05/full-report-caregiving-in-the-united-states.doi.10.26419-2Fppi.00103.001. pdf. It has been accessed December 8, 2020.
SOURCE Eli Lilly and Company
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