GHR Foundation
  • Impact Areas
    • Global Engagement >
      • Children in Families
      • Prepare The Future
      • Programs in Transition >
        • BridgeBuilder >
          • Overview
          • 2017 Top Ideas >
            • Peace Direct
            • BioCarbon Engineering
            • LIFT Chicago
            • Local Youth Corner Cameroon
            • NaTakallam
          • 2018 Top Ideas >
            • This is My Backyard
            • Found in Translation
            • Producers Direct
            • War Child Canada
            • My Choices Foundation
          • 2019 Top Ideas >
            • Top Manta
            • Five One Labs
            • SAMA for All
            • Talent Beyond Boundaries
            • FaithAction
        • Inter-Religious Action
        • Sister Support
    • Catholic Education
    • Twin Cities Racial Equity (TCRE)
    • Alzheimer's Initiative
  • News
  • About Us
    • The Foundation
    • History & Legacy
    • Team >
      • Staff
      • Committees
      • Board
    • FAQs
    • Grants & Financials
  • Contact

Press Release: Lilly Provides Update on A4 Study of Solanezumab for Preclinical Alzheimer's Disease

3/9/2023

0 Comments

 
From Eli Lilly and Company:

INDIANAPOLIS, March 8, 2023 /PRNewswire/ -- Eli Lilly and Company announced today that solanezumab did not slow the progression of cognitive decline due to Alzheimer's disease (AD) pathology when initiated in individuals with amyloid plaque but no clinical symptoms of the disease, known as the preclinical stage of AD1. Solanezumab only targets soluble amyloid beta. The treatment did not clear plaque or halt accumulation of amyloid in participants treated with the drug in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's disease (A4) Study.

"Results of the A4 Study clearly showed that the primary and secondary endpoints were not met. Therefore, the A4 Study concludes our clinical development of solanezumab and indicates that targeting soluble amyloid beta through this mechanism is not effective in this population," said John Sims, head of medical, global brand development – solanezumab, for Eli Lilly and Company. "While this study was negative, the unique data generated have increased our understanding of preclinical Alzheimer's disease and will advance the next generation of AD prevention studies. Raw data and analyses will be made widely available to researchers through the public-private partnership with the NIH-funded Alzheimer's Clinical Trial Consortium. These data will serve the scientific community and enable Lilly and other drug developers to enhance our clinical trial designs for other potential medicines targeting Alzheimer's disease."

Launched in 2013, the A4 Study was a first-of-its-kind secondary prevention trial, enrolling more than 1,100 individuals between 65 and 85 years of age who had PET-imaging evidence of amyloid plaque accumulation in the brain and who did not have clinical impairment. Participants were randomized to either solanezumab or placebo and then treated for approximately 4.5 years.

Solanezumab binds only to soluble amyloid-beta protein and was not expected to significantly remove deposited amyloid plaques. Donanemab and remternetug, other Lilly investigational antibodies currently being developed in Phase 3, are different from solanezumab in that they specifically target deposited amyloid plaque and have been shown to lead to plaque clearance in treated patients.

More than 6.5 million Americans are currently suffering dementia due to Alzheimer's disease2, and scientists expect this number to nearly triple by 20503. It is estimated that more than 20 million Americans and approximately 315 million people globally have preclinical Alzheimer's disease, the earliest stages of the disease 4, 5.

During the double-blind portion of the study, results showed:
  • Solanezumab did not slow cognitive decline on the primary outcome measure, the Preclinical Alzheimer Cognitive Composite (PACC) [mean change (95% CI): placebo -1.4 (‑1.76, ‑1.04); solanezumab -1.69 (-2.13, -1.26); p-value 0.26)]. The PACC was developed to measure the aspects of cognitive decline relevant in preclinical AD and is an equally weighted composite that tests episodic memory, timed executive function, and global cognition.
  • Secondary clinical outcome results were consistent with the primary outcome, numerically favoring placebo compared with solanezumab.
  • 36.1% of participants starting at the stage of preclinical AD progressed on the Clinical Dementia Rating-Global Scale (defined as CDR-global score greater than 0 at two consecutive visits or final visit). CDR-GS is a clinician-rated scale that provides an overall assessment of the participant's clinical stage of AD. Similar rates of progression were seen with both the solanezumab and placebo groups.
  • On amyloid PET imaging, amyloid continued to accumulate over time in both the placebo (65.9 Centiloid baseline, 17.5 Centiloid increase) and solanezumab (66.2 Centiloid baseline, 12.1 Centiloid increase) groups.
  • Higher baseline amyloid levels were strongly associated with a greater risk of progression to symptomatic Alzheimer's disease (p-value<0.001). 
  • The solanezumab and placebo groups were well-balanced at baseline, and results were consistent across multiple analysis methods and models.
  • Safety results in the A4 Study were consistent with the safety profile observed in previous solanezumab Phase 3 studies. Amyloid-Related Imaging Abnormalities with edema/effusion (ARIA-E) were uncommon and similar between treatment and placebo groups.
"These findings indicate that amyloid is a key driver of cognitive decline at the preclinical stage of Alzheimer's disease. Solanezumab did not substantially impact amyloid plaque burden in the brain, and unfortunately did not slow cognitive decline. These data suggest that we may need to be more aggressive with amyloid removal even at this very early stage of disease," said Reisa Sperling, M.D., a neurologist at the Brigham and Women's Hospital, Harvard Medical School and the A4 Study project director. "We are so very grateful to the participants, their study partners, the clinical trial site investigators and staff, and the entire study team for their longstanding dedication to this important study. It is imperative that we learn everything we can to inform ongoing and future trials in our quest to prevent memory loss due to Alzheimer's disease."

The A4 Study is a landmark public-private partnership, funded by the National Institute on Aging (part of National Institutes of Health), Eli Lilly and Company, Alzheimer's Association, GHR Foundation, Foundation for the National Institutes of Health, and several other organizations and donors. The A4 Study is coordinated by the Alzheimer's Therapeutic Research Institute (ATRI) at the Keck School of Medicine of University of Southern California and is a project of the Alzheimer's Clinical Trials Consortium (ACTC).

Full disclosure of the study results will be shared later in the year at a scientific conference.

About the A4 Study 

The Anti-Amyloid Treatment in Asymptomatic Alzheimer's disease (A4) Study is a Phase 3, double-blind, placebo-controlled study in males and females ages 65 to 85 years with preclinical AD (that is, in individuals with evidence of brain amyloid pathology on PET amyloid imaging who are clinically unimpaired but at high risk for cognitive decline). 

The A4 Study tested whether solanezumab could slow the progression of Alzheimer's disease-related cognitive decline, brain imaging, and other biomarkers over the course of approximately 4.5 years. The study included more than 1,100 participants at 67 sites throughout the United States, Japan, Canada and Australia.
0 Comments



Leave a Reply.

    Categories

    All
    A4
    Alzheimer's
    Alzheimer's Association
    BridgeBuilder
    C2N
    Catholic Schools
    Children In Families
    COVID-19
    Develop Diagnostics
    DIAN Primary Prevention
    DIAN-TU
    Education
    Global Development
    Higher Education
    Inter-Religious Action
    La Jolla Institute
    Mayo Clinic
    Mayo Clinic Study Of Aging
    NIH-NIA
    Observational Studies
    Prepare The Future
    Prevention Trials
    Sister Support
    Twin Cities Racial Equity

    Archives

    March 2023
    February 2023
    January 2023
    December 2022
    November 2022
    October 2022
    September 2022
    August 2022
    July 2022
    June 2022
    May 2022
    April 2022
    March 2022
    February 2022
    January 2022
    December 2021
    November 2021
    October 2021
    September 2021
    August 2021
    July 2021
    May 2021
    April 2021
    March 2021
    February 2021
    January 2021
    December 2020
    November 2020
    October 2020
    September 2020
    August 2020
    July 2020
    June 2020
    May 2020
    April 2020
    March 2020
    February 2020
    January 2020
    December 2019
    October 2019
    September 2019
    August 2019
    July 2019
    May 2019
    April 2019
    March 2019
    December 2018
    November 2018
    October 2018
    September 2018
    June 2018
    May 2018
    April 2018
    February 2018
    January 2018
    November 2017
    October 2017
    August 2017
    July 2017
    May 2017
    April 2017
    March 2017
    January 2017
    November 2016
    October 2016
    September 2016
    August 2016
    July 2016
    June 2016
    May 2016
    April 2016
    March 2016
    February 2016
    January 2016
    December 2015
    October 2015
    September 2015
    August 2015
    July 2015
    June 2015
    May 2015
    April 2015
    March 2015
    February 2015
    January 2015
    December 2014
    November 2014
    October 2014
    August 2014
    July 2014
    May 2014
    April 2014
    March 2014
    October 2013
    December 2012

    RSS Feed

CONNECT WITH US

IMPACT AREAS  |  NEWS  |  ABOUT  |  JOBS  | ​ CONTACT  
Privacy Policy  |  Terms of Use
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
©2023 GHR FOUNDATION
All Rights Reserved.