- Brain amyloid clearance (<24.1
Centiloids) was achieved in 37.9% of donanemab-treated participants
compared with 1.6% of
Aduhelm® (aducanumab-avwa)-treated
patients at 6 months
- Donanemab reduced brain amyloid plaque
levels vs. baseline by 65.2% compared with 17.0% for
Aduhelm® at 6 months
SAN
FRANCISCO, Nov. 30, 2022 /PRNewswire/ -- Eli Lilly
and Company (NYSE: LLY) has announced that donanemab met all
primary and secondary endpoints for the 6-month primary outcome
analysis in the Phase 3 TRAILBLAZER-ALZ 4 study, providing the
first active comparator data on amyloid plaque clearance in
patients with early symptomatic Alzheimer's disease treated with
amyloid-targeting therapies. These data comparing donanemab to
Aduhelm® * (aducanumab-avwa) to
assess superiority on amyloid plaque reduction were shared at the
15th Clinical Trials on Alzheimer's Disease (CTAD) conference.
Donanemab is an investigational antibody that targets a modified
form of beta amyloid plaque called N3pG.
Through the FDA's accelerated approval pathway, the FDA has
recognized that the reduction of amyloid beta plaque is a biomarker
reasonably likely to predict clinical benefit in the treatment of
early Alzheimer's disease.
"The purpose of this first ever active comparator trial of
amyloid lowering agents was to answer important questions about
potential differences in amyloid plaque reduction," said
Mark Mintun, M.D., group vice
president of pain and neurodegeneration research and development,
Eli Lilly and Company. "These data reinforce our confidence in
donanemab's unique mechanism of action based on reductions in key
biomarkers of Alzheimer's disease, amyloid plaque and plasma
phosphorylated tau (P-tau). Importantly, this was also the first
study to obtain ARIA rates side by side using identical methods for
ARIA assessment in the same patient population, demonstrating the
ability to disconnect rate of plaque clearance from rate of ARIA
incidence."
In the co-primary outcomes, brain amyloid plaque clearance,
defined as achieving brain amyloid plaque levels of <24.1
Centiloids, was achieved in 37.9% of donanemab-treated participants
(25 of 66) compared with 1.6% of Aduhelm-treated patients (1 of 64)
at 6 months; in the intermediate tau subpopulation, 38.5% of
donanemab-treated participants (10 of 26) reached brain amyloid
clearance compared with 3.8% of Aduhelm-treated participants (1 of
26) by 6 months. In a key secondary outcome, donanemab reduced
brain amyloid levels vs. baseline by 65.2% compared with 17.0% for
Aduhelm at 6 months. In an exploratory outcome, donanemab, but not
aducanumab-avwa, treatment significantly reduced plasma P-tau217 at
6 months compared to baseline.
The safety profile of both treatments was consistent with their
previously published studies. ARIA was the most common treatment
emergent adverse event in both groups. In the aducanumab-avwa
group, the incidence of total ARIA was 26.1% with 4.3% being
symptomatic. In the donanemab group, the incidence of total ARIA
was 25.4% with 2.8% being symptomatic. For both treatments, all
symptomatic cases were related to ARIA-E.
"It is encouraging to see that donanemab produced significant
reduction of amyloid build up in the brain and P-tau in the blood
after 6 months. This suggests that this treatment modified the
biology of Alzheimer's disease early on in treatment," said
Stephen Salloway, MD, associate
director of the Center for Alzheimer's Disease Research at
Brown University, who presented the
findings. "It is also notable in TRAILBLAZER-ALZ 4 that the higher
amyloid clearance by donanemab compared to aducanumab-avwa at 6
months was not associated with a higher rate of ARIA."
TRAILBLAZER-ALZ 4 is ongoing and will have 12-month and 18-month
secondary analyses. The study is one of five studies that comprise
the clinical program to evaluate the efficacy and safety of
donanemab. In August, Lilly announced that the FDA accepted the
donanemab application for review, with Priority Review designation,
for Alzheimer's disease under the accelerated approval pathway.
About TRAILBLAZER-ALZ 4 Study
TRAILBLAZER-ALZ 4
(LY3002813) is a multicenter, randomized, open-label Phase 3 study
of that enrolled 148 patients aged 50 to 85 with early symptomatic
AD who met entry criteria including a Clinical Dementia Rating
(CDR)-Global Score of 0.5 or 1 and gradual and progressive change
in memory function for more than six months, among other criteria.
Donanemab and Aduhelm are administered via intravenous infusions
every four weeks for up to 18 months. Donanemab is administered
until evidence of plaque clearance via positron emission tomography
(PET) at 6, 12, or 18 months. Aduhelm is administered through the
duration of the study according to its approved label. The studies'
co-primary endpoints are superiority on, as measured by PET scan:
the percentage of participants who reach complete amyloid plaque
clearance and the percentage of participants who reach complete
amyloid plaque clearance in the intermediate tau subpopulation at 6
months.
Lilly previously announced and published in the New England
Journal of Medicine (NEJM) results from the Phase 2 TRAILBLAZER-ALZ
study in March 2021. In June 2021, Lilly announced that the FDA had
granted Breakthrough Therapy designation for donanemab based on the
TRAILBLAZER-ALZ data.
About Alzheimer's Disease
Alzheimer's disease is a
fatal illness 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 to 80 percent of
all cases1. There are currently over 55 million people
living with dementia around the world, with numbers expected to
increase to nearly 139 million by 20502. Over 10 million
new cases of dementia are diagnosed each year worldwide, implying
one new case every 3.2 seconds, and a significant increase in the
caregiving burden placed on society and families. In the US alone,
there was an increase of nearly 10 million new caregivers from 2015
to 20203. The current annual societal and economic cost
of dementia is estimated at $1.3
trillion, an amount that is expected to double by 2030
unless we find a way to slow the disease2.
About Lilly
Lilly unites caring with discovery to
create medicines that make life better for people around the world.
We've been pioneering life-changing discoveries for nearly 150
years, and today our medicines help more than 47 million
people across the globe. Harnessing the power of biotechnology,
chemistry and genetic medicine, our scientists are urgently
advancing new discoveries to solve some of the world's most
significant health challenges, redefining diabetes care, treating
obesity and curtailing its most devastating long-term effects,
advancing the fight against Alzheimer's disease, providing
solutions to some of the most debilitating immune system disorders,
and transforming the most difficult-to-treat cancers into
manageable diseases. With each step toward a healthier world, we're
motivated by one thing: making life better for millions more
people. That includes delivering innovative clinical trials that
reflect the diversity of our world and working to ensure our
medicines are accessible and affordable. To learn more,
visit Lilly.com and Lilly.com/newsroom or
follow us on Facebook, Instagram, and LinkedIn. P-LLY
© Lilly USA,
LLC 2022. ALL RIGHTS RESERVED.
*Other company and product names are trademarks of their
respective owners.
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 Lilly's 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 undertaking,
there are substantial risks and uncertainties in the process of
drug research, development, and commercialization. Among other
things, there is no guarantee that future study results will be
consistent with study findings to date, that donanemab will prove
to be a safe and effective treatment, or that donanemab will
receive regulatory approval. For 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 undertakes no duty to update
forward-looking statements to reflect events after the date of this
release.
- Alzheimer's Association. 2022 Alzheimer's Disease Facts and
Figures.
https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf. Accessed May
12, 2022.
- Alzheimer's Disease International. Dementia
Statistics. https://www.alzint.org/about/dementia-facts-figures/dementia-statistics/.
Accessed May 12, 2022.
- AARP. 2020 Report: Caregiving in 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 May 12, 2022.
Refer
to:
|
Kristen Basu;
kbasu@lilly.com; (317) 447-2199 (Media)
|
|
Joe Fletcher;
jfletcher@lilly.com; (317) 296-2884 (Investors)
|
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SOURCE Eli Lilly and Company