Lilly’s donanemab slowed Alzheimer’s disease progression in Phase 2 trial: full data presented at AD/PD™ 2021 and published in NEJM | Antibodies

INDIANAPOLIS, IN, USA I March 13, 2021 I Section 2 TRAILBLAZER-ALZ outcomes introduced at present by Eli Lilly and Firm (NYSE: LLY) on the fifteenth Worldwide Convention on Alzheimer’s & Parkinson Ailments™ 2021 (AD/PD™ 2021) held just about March 9-14, 2021 and printed concurrently within the New England Journal of Medicine (NEJM)  develop on beforehand reported top-line knowledge that discovered donanemab met its major endpoint and confirmed vital slowing of decline on the built-in Alzheimer’s Illness Ranking Scale (iADRS), a composite measure of cognition and every day operate, in sufferers with early symptomatic Alzheimer’s illness in comparison with placebo^1,2.

Moreover, knowledge from secondary analyses confirmed donanemab constantly slowed cognitive and purposeful decline, with ranges between 20-40 p.c 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 a number of occasions in comparison with placebo. Additional, prespecified exploratory analyses confirmed donanemab slowed the buildup of tau throughout key mind areas in sufferers affected by Alzheimer’s illness.  

“We’re assured within the outcomes of the TRAILBLAZER-ALZ examine,” stated Daniel Skovronsky, M.D., Ph.D., Lilly’s chief scientific officer and president of Lilly Analysis Laboratories. “That is the primary late-stage examine in Alzheimer’s illness to fulfill its major endpoint on the major evaluation. Donanemab has the potential to turn into an important therapy for Alzheimer’s illness. We had been happy to see not solely slowing of cognitive and purposeful decline, but in addition very substantial clearance of amyloid plaques and slowing of unfold of tau pathology. The constellation of scientific and biomarker outcomes signifies the potential for long-term illness modification. We’re grateful to the sufferers, caregivers, and investigators who participated on this landmark examine.”

Particularly, at 76 weeks in comparison with baseline, therapy with donanemab slowed decline by 32 p.c in comparison with placebo as measured by the iADRS, which was statistically vital. As early as 9 months (36 weeks) after initiation of therapy, a major distinction in decline by iADRS was noticed.

As well as, 40 p.c of contributors handled with donanemab achieved amyloid negativity as early as six months after beginning therapy and 68 p.c achieved this goal by 18 months. Donanemab is a monoclonal antibody that was designed to bind a particular type of post-translationally modified Aß, N-terminal pyroglutamate, and thereby yield fast and full clearance of amyloid plaques. 

“Tau has turn into more and more validated as a predictive biomarker for Alzheimer’s illness development, as proven once more on this trial,” stated Liana G. Apostolova, M.D., M.Sc., FAAN, Indiana College (IU) Distinguished Professor and Barbara and Peer Baekgaard Professor in Alzheimer’s Illness Analysis at IU College of Medication. “A key perception of the outcomes from the TRAILBLAZER-ALZ examine is that donanemab not solely considerably diminished the quantity of amyloid deposition in these sufferers but in addition slowed the scientific development of the illness suggesting that this may very well be a disease-modifying remedy. We consider these amyloid and tau imaging knowledge lay the muse for precision medicine-based Alzheimer’s illness therapies.”

The protection profile of donanemab was in step with observations from Section 1 knowledge. Within the donanemab therapy group, amyloid-related imaging abnormalities – edema (ARIA-E) occurred in 26.7 p.c of handled contributors, with an general incidence of 6.1 p.c experiencing symptomatic ARIA-E; the bulk ARIA-E instances occurred throughout the first 12 weeks after initiation of therapy. Different widespread AEs within the donanemab therapy group embody ARIA-H associated occasions like microhemorrhages (7.6 p.c) and superficial siderosis of central nervous system (13.7 p.c), nausea (10.7 p.c), and infusion-related response (IRR) (7.6 p.c). Critical IRR or hypersensitivity occurred in 2.3 p.c of contributors handled with donanemab. Within the donanemab arm, 30.5 p.c of sufferers discontinued therapy attributable to an opposed occasion and half of those discontinuations had been attributable to ARIA-related occasions. Sufferers with therapy discontinuations had been allowed to proceed within the trial.

“As a clinician and researcher, I am notably inspired by the numerous plaque reducing and the slowing of scientific decline with donanemab,” stated Stephen P. Salloway, M.S., M.D., Director of the Reminiscence and Getting older Program and the Division of Neurology at Butler Hospital and Martin M. Zucker professor of Psychiatry and Human Conduct, Division of Neurology, Warren Alpert Medical College of Brown College. “The donanemab outcomes are a major and inspiring milestone for individuals impacted by Alzheimer’s illness and we’re wanting to proceed on on this struggle.”

Discussions with regulators are ongoing and an replace on the TRAILBLAZER scientific trial program shall be offered on a webcast on Monday, March 15 at 10:30 AM EDT together with an replace on the continuing TRAILBLAZER-ALZ 2 trial. To study extra in regards to the TRAILBLAZER-ALZ 2 examine or to see if you happen to prequalify, go to www.trailblazer2study.com.

About TRAILBLAZER-ALZ Examine
TRAILBLAZER-ALZ (NCT03367403) is a randomized, placebo-controlled, double-blind, multi-center Section 2 examine to evaluate the protection, tolerability and efficacy of donanemab in sufferers with early symptomatic Alzheimer’s illness. The trial enrolled 272 sufferers who had been chosen based mostly on cognitive assessments along with amyloid plaque imaging and tau staging by PET imaging. The examine’s major endpoint is change from baseline till 76 weeks within the Built-in Alzheimer’s Illness Ranking Scale (iADRS), a composite instrument combining the Alzheimer’s Illness Evaluation Scale-Cognitive subscale (ADAS-Cog13) and the Alzheimer’s Illness Cooperative Examine – instrumental Actions of Day by day Dwelling (ADCS-iADL) for operate. Key secondary endpoints embody adjustments between baseline and 76 weeks within the Alzheimer’s Illness Evaluation Scale-Cognitive Subscale (ADAS-Cog13), ADCS-iADL, MMSE, and Medical Dementia Ranking Scale Sum of Bins (CDR-SB) scores. Different secondary biomarker endpoints embody adjustments from baseline to week 76 in mind amyloid deposition and mind tau deposition and volumetric MRI. The protection, tolerability and efficacy of donanemab are additionally being evaluated within the ongoing randomized, placebo-controlled, double-blind, multi-center Section 2 examine TRAILBLAZER-ALZ 2 (NCT04437511).

About Alzheimer’s Illness
Alzheimer’s illness is a deadly sickness that causes progressive decline in reminiscence and different points of cognition. Dementia attributable to Alzheimer’s illness is the most typical type of dementia, accounting for 60 to 80 p.c of all instances³. There are at present over 50 million individuals residing with dementia around the globe, with numbers anticipated to extend to almost 152 million by 2050⁴. Nearly 10 million new instances of dementia are identified annually worldwide, implying one new case each 3 seconds, and a major enhance within the caregiving burden positioned on society and households. Within the US alone, there was a rise of 8 million new caregivers from 2015 to 2020⁵. The present annual societal and financial value of dementia is estimated at $1 trillion, an quantity that’s anticipated to double by 2030 except we discover a method to gradual the illness⁴.

About Eli Lilly and Firm
Lilly is a worldwide healthcare chief that unites caring with discovery to make life higher for individuals around the globe. We had been based greater than a century in the past by a person dedicated to creating high-quality medicines that meet actual wants, and at present we stay true to that mission in all our work. Throughout the globe, Lilly staff work to find and produce life-changing medicines to those that want them, enhance the understanding and administration of illness, and provides again to communities by way of philanthropy and volunteerism. To study extra about Lilly, please go to us at lilly.com and lilly.com/newsroom. P-LLY

1. Mintun M, Lo AC, et. al. Donanemab Slows Development of Early Symptomatic Alzheimer’s Illness in Section 2 Proof of Idea Trial. Offered just about on the Worldwide Convention on Alzheimer’s & Parkinson Ailments™ 2021 (AD/PD™ 2021); March 9-14.
2. Mintun M, Lo AC, et. al. (2021). Donanemab in Early Alzheimer’s Illness. New England Journal of Medication, https://www.nejm.org/doi/full/10.1056/NEJMoa2100708. 
3. Alzheimer’s Affiliation. Information and Figures. https://www.alz.org/alzheimers-dementia/facts-figures. Accessed December 8, 2020.
4. Alzheimer’s Illness Worldwide. World Alzheimer Report 2019. https://www.alz.co.uk/research/WorldAlzheimerReport2019.pdf. Accessed December 8, 2020.
5. AARP. 2020 Report: Caregiving within 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.

SOURCE: Eli Lilly