full data presented at AD / PD ™ 2021 and published in NEJM

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INDIANAPOLIS, March 13, 2021 / PRNewswire / – TRAILBLAZER-ALZ Phase 2 results presented today by Eli Lilly and Company (NYSE: LLY) at the 15th International Conference on Alzheimer’s Disease and Parkinson’s ™ 2021 (AD / PD ™ 2021) held virtually March 9-14, 2021 and published simultaneously in the New England Journal of Medicine (NEJM) expand on previously reported high-level data that revealed donanemab met its primary endpoint and showed significant slowing of decline on the Integrated Alzheimer’s Disease Assessment Scale (iADRS) , a composite measure of cognition and daily function, in patients with early symptomatic Alzheimer’s disease. disease versus placebo^1.2.

In addition, data from secondary analyzes showed that donanemab consistently slowed cognitive and functional decline, with ranges between 20% and 40% for 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, predefined exploratory analyzes have shown that donanemab slows the build-up of tau in key regions of the brain in patients with Alzheimer’s disease.

“We are confident in the results of the TRAILBLAZER-ALZ study,” said Daniel Skovronsky, MD, Ph.D., Scientific Director of Lilly and President of Lilly Research Laboratories. “This is the first advanced stage Alzheimer’s disease study to meet its primary endpoint in the primary analysis. Donanemab has the potential to become a very important treatment for Alzheimer’s disease. We have was pleased to see not only a slowing of cognitive and functional decline, but also a very significant clearance of amyloid plaques and a slowing of the spread of tau pathology. The constellation of clinical findings and biomarkers indicate the potential for disease modification long-term. We thank the patients, caregivers and researchers who participated in this landmark study. “

Specifically, at 76 weeks from baseline, treatment with donanemab slowed the decline by 32% compared to placebo as measured by iADRS, which was statistically significant. As early as nine months (36 weeks) after the start of treatment, a significant difference in decline with 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 goal within 18 months. Donanemab is a monoclonal antibody that has been designed to bind to a specific form of post-translational modified N-terminal Aβ pyroglutamate, thereby producing rapid and complete clearance of amyloid plaques.

“Tau is increasingly validated as a predictive biomarker for the progression of Alzheimer’s disease, as again shown by this trial,” said Liana G. Apostolova, MD, M.Sc., FAAN, Indiana University (IU) Professor Emeritus and Barbara and Peer Baekgaard Professor of Alzheimer’s Disease Research at the IU School of Medicine. A key 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 it could be a DMARD. We believe these amyloid and tau imaging data lay the foundation for precision medicine-based treatments for Alzheimer’s disease. ”

The safety profile of donanemab was consistent with the observations of the Phase 1 data. In the donanemab treatment group, imaging abnormalities related to amyloid – edema (ARIA-E) occurred in 26.7% of patients. treated participants, with an overall incidence of 6.1% showing symptoms of ARIA-E; the majority of ARIA-E cases have occurred within the first 12 weeks after starting treatment. Other common AEs 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 infusion-related reactions (IRR) (7.6%). Severe IRR or hypersensitivity occurred in 2.3% of participants treated with donanemab. In the donanemab arm, 30.5% of patients discontinued treatment due to an adverse event and half of these discontinuations were due to ARIA-related events. Patients who discontinued treatment were allowed to continue the trial.

“As a clinician and researcher, I am particularly encouraged by the significant reduction in dental plaque and the slowing of clinical decline with donanemab,” said Stephen P. Salloway, MS, MD, Director of the Memory and Aging Program and Department of Neurology 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 step for those affected by Alzheimer’s disease and we look forward to continuing this fight.

Discussions with regulators are ongoing and an update on the TRAILBLAZER clinical trials program will be webcast at Monday March 15 at 10:30 a.m. EDT including an update on the ongoing TRAILBLAZER-ALZ 2 trial. To learn more about the TRAILBLAZER-ALZ 2 study or to see if you shortlist, visit www.trailblazer2study.com.

About the TRAILBLAZER-ALZ study
TRAILBLAZER-ALZ (NCT03367403) is a phase 2, randomized, placebo-controlled, double-blind, multicenter study to evaluate 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 associated with amyloid plaque imaging and tau staging by PET imaging. The primary endpoint of the study is change from baseline up to 76 weeks in the Integrated Alzheimer’s Disease Assessment Scale (iADRS), a composite tool combining the sub- Alzheimer’s Disease Rating Scale – Cognitive Subscale (ADAS-Cog13) and Alzheimer’s Cooperative Study – Instrumental Activities of Daily Living (ADCS-iADL) for function. Primary secondary endpoints include changes from baseline to 76 weeks in Alzheimer’s-Cognitive Subscale (ADAS-Cog13), ADCS-iADL, MMSE, and Clinical Dementia Rating scores. Scale Sum of Boxes (CDR-SB). Other secondary biomarker parameters include changes between baseline and week 76 in cerebral amyloid deposition and cerebral tau deposition and volumetric MRI. The safety, tolerability and efficacy of donanemab are also being evaluated in the phase 2, randomized, placebo-controlled, double-blind, multicenter study TRAILBLAZER-ALZ 2 (NCT04437511).

About Alzheimer’s disease
Alzheimer’s disease is a fatal disease 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 60-80% of all cases³. There are currently over 50 million people living with dementia worldwide, and the number is expected to increase to nearly 152 million by 2050⁴. Almost 10 million new cases of dementia are diagnosed each year worldwide, implying a new case every 3 seconds and a significant increase in the burden of caregiving on society and families. In the United States 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 $ 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 global healthcare leader who combines compassion and discovery to improve the lives of people around the world. We were founded over a century ago by a man determined to create high quality medicines that meet real needs, and today we remain true to that mission in all of our work. Around the world, Lilly employees strive to discover and bring life-changing medicines to those in need, to improve understanding and management of disease, and to give back to communities through philanthropy and volunteering. To learn more about Lilly, please visit us at lilly.com and lilly.com/newsroom. P-LLY

Lilly Cautionary Statement 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 the Lilly’s Alzheimer’s disease platform, including donanemab as a potential treatment for people with Alzheimer’s disease. Early symptomatic Alzheimer’s and reflects Lilly’s current beliefs and expectations. However, as with any such endeavor, there are substantial risks and uncertainties in the process of drug research, development and commercialization. Among other things, there can be no assurance that the results of future studies 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 on these and other risks and uncertainties, see Forms 10-K and 10-Q filed by Lilly with the United States Securities and Exchange Commission. Except as required by law, Lilly assumes no obligation to update any forward-looking statements to reflect events subsequent to the date of this release.

Mintun M, Lo AC, et. Al. Donanemab Slows Progression of Early Symptomatic Alzheimer’s Disease in Phase 2 Demonstration-of-Principle Trial. Presented virtually at the International Conference on Alzheimer’s Disease and Parkinson’s ™ 2021 (AD / PD ™ 2021); March 9-14.
Mintun M, Lo AC, et. Al. (2021). Donanemab in early-onset Alzheimer’s disease. New England Journal of Medicine, https://www.nejm.org/doi/full/10.1056/NEJMoa2100708.
Alzheimer Association. Facts and Figures. https://www.alz.org/alzheimers-dementia/facts-figures. Accessed December 8, 2020.
Alzheimer’s Disease International. World Alzheimer’s Disease Report 2019. https://www.alz.co.uk/research/WorldAlzheimerReport2019.pdf. Accessed December 8, 2020.
AARP. Report 2020: Caregiving in the United States 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.

SOURCE Eli Lilly and company

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