INDIANAPOLIS March 13, 2021 / PRNewswire / – Phase 2 TRAILBLAZER-ALZ Results Presented Today by Eli Lilly and Company (NYSE: LLY) at 15th International Conference on Alzheimer’s and Parkinson’s Disease ™ 2021 (AD / PD ™ 2021) held virtually March 9-14, 2021 and published simultaneously in the New England Journal of Medicine (NEJM) expands on previously reported top-line data showing that donanemab met the primary endpoint and showed a significant delay in deterioration on the Integrated Alzheimer’s Disease Rating Scale (iADRS), a composite measure of cognition and daily functioning, in patients with early symptomatic Alzheimer’s disease compared to placebo1.2
In addition, data from secondary analyzes showed that donanemab showed consistently delayed cognitive and functional decline, with a range 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 time points compared to placebo. Furthermore, pre-specified exploratory analyzes showed that donanemab slowed tau accumulation in key brain regions in Alzheimer’s disease patients.
“We are confident in the results of the TRAILBLAZER-ALZ study,” said Daniel Skovronsky, MD, Ph.D., Lilly’s Chief Scientific Officer and President of Lilly Research Laboratories. “This is the first late-stage Alzheimer’s study to reach the primary endpoint in the primary analysis. Donanemab has the potential to become a very important treatment for Alzheimer’s. We were delighted that not only cognitive and functional decline was delayed, but also very substantial clearance of amyloid plaques and delay in the spread of tau pathology. The constellation of clinical and biomarker results indicates the potential for long-term disease modification. We are the patients , caregivers and researchers who participated in this groundbreaking study. “
Specifically, after 76 weeks compared to baseline, donanemab treatment 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 reduction due to iADRS was observed.
In addition, 40 percent of the participants treated with donanemab achieved amyloid negativity as early as six months after starting treatment, and 68 percent reached this goal after 18 months. Donanemab is a monoclonal antibody designed to bind a specific form of post-translational modified Aβ, N-terminal pyroglutamate, to provide rapid and complete clearance of amyloid plaques.
“Tau is increasingly being validated as a predictive biomarker for the progression of Alzheimer’s disease, as shown again in this study,” said Liana G. Apostolova, MD, M.Sc., FAAN, Indiana University (IU) Distinguished Professor and Barbara and Peer Baekgaard Professor of Alzheimer’s Disease Research at the IU School of Medicine. “An important insight into 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 this could be a disease modifying therapy. These amyloid and tau imaging data form the basis for precision drug-based treatments of Alzheimer’s disease. ”
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 the treated participants, with an overall incidence of 6.1 percent with symptomatic ARIA-E; most cases of ARIA-E occurred within the first 12 weeks of starting treatment. Other common adverse reactions in the donanemab treatment group include ARIA-H-related events such as microhemorrhage (7.6 percent) and superficial central nervous system siderosis (13.7 percent), nausea (10.7 percent), and infusion-related reaction (IRR) (7.6 percent). Severe IRR or hypersensitivity occurred in 2.3 percent of the participants treated with donanemab. In the donanemab arm, 30.5 percent of patients discontinued treatment due to an adverse reaction and half of these discontinuations were due to ARIA-related events. Patients who had discontinued treatment were allowed to continue with the study.
“As a clinician and researcher, I am especially encouraged by the significant reduction in plaque and the delay in clinical deterioration with donanemab,” said Stephen P. Salloway, MS, MD, director of the memory and aging program and neurology department at Butler Hospital and Martin M. Zucker Professor of Psychiatry and Human Behavior, Department of Neurology, Warren Alpert Medical School of Brown University“The results of donanemab are an important and encouraging milestone for people affected by Alzheimer’s disease and we would like to continue this battle.”
Discussions with regulatory authorities are ongoing and an update on the TRAILBLAZER clinical trial program will be provided via webcast at Monday, March 15 Bee 10:30 am EDT including an update on the ongoing TRAILBLAZER-ALZ 2 study. Visit www.trailblazer2study.com to learn more about the TRAILBLAZER-ALZ 2 study or to see if you are pre-qualifying.
About the 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 study enrolled 272 patients selected based on cognitive assessments in combination with amyloid plaque imaging and tau staging by PET imaging. The primary endpoint of the study is the change from baseline to week 76 in the Integrated Alzheimer’s Disease Rating Scale (iADRS), a composite tool that combines the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog13) with the Alzheimer’s Disease Cooperative Study – instrumental Activities of Daily Living (ADCS-iADL) for function. Major secondary endpoints include changes between baseline and week 76 in 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 included 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 trial TRAILBLAZER-ALZ 2 (NCT04437511).
About Alzheimer’s
Alzheimer’s disease is a deadly disease that causes gradual decline in memory and other aspects of cognition. Alzheimer’s dementia is the most common form of dementia, accounting for 60 to 80 percent of all cases3There are currently more than 50 million people with dementia worldwide, and the number is expected to increase to nearly 152 million by 20504Worldwide, nearly 10 million new cases of dementia are diagnosed every year, meaning one new case every 3 seconds, and a significant increase in community and family care. In the US alone, there was an increase of 8 million new healthcare providers between 2015 and 20205The current annual social and economic costs of dementia are estimated at $ 1 trillion, an amount expected to double by 2030 unless we find a way to slow the disease4
About Eli Lilly and Company
Lilly is a global healthcare leader who unites care and discovery to make the lives of people around the world better. We were founded more than a century ago by a man dedicated to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Around the world, Lilly employees work to discover and bring life-changing drugs to those who need them, to improve understanding and management of disease, and to give back to communities through philanthropy and volunteerism. To learn more about Lilly, visit lilly.com and lilly.com/newsroom. P-LLY
Lilly caution regarding forward-looking statements
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Lilly’s Alzheimer’s disease platform, including donanemab as a potential treatment for people with early symptomatic Alzheimer’s disease and reflects current beliefs and expectations of Lilly. However, as with any such venture, there are significant risks and uncertainties in the drug research, development and commercialization process. Among other things, there is no guarantee that future research results will be consistent with research results to date, that donanemab will prove to be a safe and effective treatment, or that donanemab will receive regulatory approval. For a further discussion of these and other risks and uncertainties, see Lilly’s Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly is under no obligation to update forward-looking statements to reflect events after the date of this press release.
- Mintun M, Lo AC, et. al. Donanemab slows progression of early symptomatic Alzheimer’s disease in Phase 2 Proof of Concept study. Presented virtually at the International Conference on Alzheimer’s & Parkinson Diseases ™ 2021 (AD / PD ™ 2021); March 9-14
- 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 numbers. https://www.alz.org/alzheimers-dementia/facts-figures. Enter December 8, 2020
- Alzheimer’s Disease International. World Alzheimer Report 2019.https: //www.alz.co.uk/research/WorldAlzheimerReport2019.pdf. Enter December 8, 2020
- AARP. Report 2020: 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. Enter December 8, 2020
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