AMG 133 is a First-in-Class
Investigational Bispecific Molecule That Activates GLP-1R
and Inhibits GIPR
Phase 1 Results Showed up to 14.5% Reduction
in Body Weight at the Highest Dose After 12 Weeks
Initiating Phase 2 Study in Early 2023
THOUSAND
OAKS, Calif., Dec. 1, 2022
/PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced new Phase 1
data from AMG 133, a novel bispecific glucose-dependent
insulinotropic polypeptide receptor (GIPR) antagonist and
glucagon-like peptide-1 (GLP-1) receptor agonist molecule. This
first-in-human study was designed to evaluate the safety,
tolerability, pharmacokinetic and pharmacodynamic effects of AMG
133 in people with obesity and without diabetes (NCT04478708).
These data will be presented as part of an oral presentation on
Saturday, Dec. 3 at the
20th World Congress of Insulin Resistance, Diabetes and
Cardiovascular Disease (WCIRDC) Hybrid Conference.
"AMG 133 was designed based on preclinical and human genetic
data that strongly suggest GIPR inhibition as a strategy for weight
loss, especially in combination with GLP-1 agonism," said
David M. Reese, M.D., executive vice
president of Research and Development at Amgen. "We are encouraged
by these Phase 1 results with once-monthly dosing of AMG 133,
specifically, the degree, rate and durability of the weight loss.
We look forward to initiating the Phase 2 study early next
year."
Participants were randomized (3:1) to receive subcutaneous AMG
133 or placebo either as a single ascending dose (SAD) or multiple
ascending doses (MAD). The MAD cohorts showed mean percent changes
in body weight (BW), ranging from -7.2% at the lowest dose (140mg
Q4W), to -14.5% at the highest dose (420mg Q4W) by day 85. A
substantial degree of weight loss was maintained beyond the
treatment period, which will be shared as part of the oral
presentation. Most treatment emergent adverse events (TEAEs) were
mild and transient. The majority of the TEAEs were GI-related with
the most common being nausea and vomiting, most events resolved
within 48 hours. Based on these data, a Phase 2 trial will be
initiated early next year to further study the attributes of this
molecule.
Amgen will host a webcast call for the investment community in
conjunction with WCIRDC at 8:00 a.m. ET on
Monday, Dec. 5, 2022. For more information visit:
https://investors.amgen.com/.
About Obesity
Obesity is a serious, chronic disease
that affects a significant proportion of the world population. In
the US alone, 74% of adults are either obese or
overweight1, including 42% who are obese2.
The worldwide prevalence of obesity has tripled over the past 40
years and continues to rise in nearly every
demographic.3 Obesity is linked to a marked reduction in
quality of life and an array of serious medical
complications4, placing a significant burden on
healthcare systems globally.5 Despite the scale of the
disease, the formal recognition of obesity as a chronic disease by
the American Medical Association (2013) and the European Health
Commission (2021), and medical guidelines recommending
pharmacologic treatment in appropriate individuals, only 1-3% of
patients globally are prescribed medication.6,7
About AMG 133
AMG 133 is a bispecific
glucose-dependent insulinotropic polypeptide receptor (GIPR)
antagonist and glucagon-like peptide-1 (GLP-1) receptor agonist
molecule. AMG 133 mimics the agonist effects of GLP-1 and
antagonizes the effects of glucose-dependent insulinotropic
polypeptide (GIP). Amgen moved into this Phase 1 study based on
human genetic insights and preclinical evidence that suggested
synergistic effects with GIP receptor blockade and GLP-1 receptor
agonism on weight loss and improvement in other metabolic
parameters.
About the Phase 1 Study and Future Development
The
randomized, double-blind, placebo-controlled single and multiple
ascending dose study of AMG 133 enrolled people with a Body Mass
Index (BMI) of ≥30.0 kg/m2 and ≤40.0 kg/m2 without other medical
conditions. Participants were randomized (3:1) to receive
subcutaneous AMG 133 or placebo either as a single ascending dose
(SAD) or multiple ascending doses (MAD). Participants were assigned
to six SAD cohorts (n=49; mean age 48 years, BMI 33.4 kg/m2, and BW
99.5 kg) and three MAD cohorts (n=26; mean age 46 years, BMI 33.5
kg/m2, and BW 96.9 kg). Pharmacokinetics and body weight (BW) were
measured and safety and tolerability were monitored. Most treatment
emergent adverse events (TEAEs) were mild and
transient.8 The majority of the TEAEs were GI-related
with the most common being nausea and vomiting, most events
resolved within 48 hours.
Amgen plans to initiate Phase 2 testing with a dose-ranging
study in early 2023, where long-term effects in an expanded number
of patients will be further characterized.
About Amgen
Amgen is committed to unlocking the potential of biology for
patients suffering from serious illnesses by discovering,
developing, manufacturing and delivering innovative human
therapeutics. This approach begins by using tools like advanced
human genetics to unravel the complexities of disease and
understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and
leverages its expertise to strive for solutions that improve health
outcomes and dramatically improve people's lives. A biotechnology
pioneer since 1980, Amgen has grown to be one
of the world's leading independent biotechnology
companies, has reached millions of patients around the world and is
developing a pipeline of medicines with breakaway
potential.
Amgen is one of the 30 companies that comprise the Dow
Jones Industrial Average and is also part of the Nasdaq-100 index.
In 2022, Amgen was named one of the "World's Best Employers" by
Forbes and one of "America's 100 Most Sustainable Companies" by
Barron's.
For more information, visit Amgen.com and follow us
on Twitter, LinkedIn, Instagram, TikTok and YouTube.
Amgen Forward-Looking Statements
This news release
contains forward-looking statements that are based on the current
expectations and beliefs of Amgen. All statements, other than
statements of historical fact, are statements that could be deemed
forward-looking statements, including any statements on the
outcome, benefits and synergies of collaborations, or potential
collaborations, with any other company (including BeiGene, Ltd.,
Kyowa-Kirin Co., Ltd., or any collaboration to manufacture
therapeutic antibodies against COVID-19), the performance of
Otezla® (apremilast) (including anticipated Otezla sales growth and
the timing of non-GAAP EPS accretion), the Five Prime Therapeutics,
Inc. acquisition, the Teneobio, Inc. acquisition, or the recently
announced proposed acquisition of ChemoCentryx, Inc., or the
ChemoCentryx, Inc. acquisition, as well as estimates of revenues,
operating margins, capital expenditures, cash, other financial
metrics, expected legal, arbitration, political, regulatory or
clinical results or practices, customer and prescriber patterns or
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pandemics or other widespread health problems such as the ongoing
COVID-19 pandemic on our business, and other such estimates and
results. Forward-looking statements involve significant risks and
uncertainties, including those discussed below and more fully
described in the Securities and Exchange Commission reports filed
by Amgen, including our most recent annual report on Form 10-K and
any subsequent periodic reports on Form 10-Q and current reports on
Form 8-K. Unless otherwise noted, Amgen is providing this
information as of the date of this news release and does not
undertake any obligation to update any forward-looking statements
contained in this document as a result of new information, future
events or otherwise.
No forward-looking statement can be guaranteed and actual
results may differ materially from those we project. Discovery or
identification of new product candidates or development of new
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from concept to product is uncertain; consequently, there can be no
guarantee that any particular product candidate or development of a
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Our results may be affected by our ability to successfully
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CONTACT: Amgen, Thousand
Oaks
Jessica Akopyan, 805-440-5721
(media)
Arvind Sood, 805-447-1060
(investors)
1 Fryar,
C.D., Carroll., M.D., Afful, J. (2020). Prevalence of overweight,
obesity, and severe obesity among adults aged 20 and over: United
States, 1960–1962 through 2017–2018. NCHS Health E-Stats.
https://www.cdc.gov/nchs/data/hestat/obesity-adult-17-18/overweight-obesity-adults-H.pdf.
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2 Stierman,
B., Afful, J., Carroll, M.D., Chen, T.C., Davy, O., Fink, S.,
Fryar, C.D., Gu, Q., Hales, C.M., Hughes, J.P., Ostchega, Y.,
Storandt., R.J., Akinbami, L.J. (2021). National Health and
Nutrition Examination Survey 2017–March 2020 Prepandemic Data Files
Development of Files and Prevalence Estimates for Selected Health
Outcomes. National Health Statistics Reports, NHSR No. 158.
https://stacks.cdc.gov/view/cdc/106273.
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3 World
Health Organization. Obesity and overweight fact sheet.
https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
Accessed November 2022.
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4 Centers
for Disease Control and Prevention. Consequences of Obesity.
https://www.cdc.gov/obesity/basics/consequences.html. Accessed
November 2022.
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5 Hecker,
J., Freijer, K., Hiligsmann, M. et al. (2022). Burden of disease
study of overweight and obesity; the societal impact in terms of
cost-of-illness and health-related quality of life. BMC Public
Health, 22, 46.
https://doi.org/10.1186/s12889-021-12449-2.
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6
Samaranayake NR, Ong KL, Leung RY, Cheung BM. Management of obesity
in the National Health and Nutrition Examination Survey (NHANES),
2007–2008. Ann Epidemiol 2012;22(5):349–53.
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7 Xia Y,
Kelton CM, Guo JJ, Bian B, Heaton PC. Treatment of obesity:
Pharmacotherapy trends in the United States from 1999 to 2010.
Obesity (Silver Spring) 2015;23(8):1721–8.
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8
ClinicalTrials.gov. Single and Multiple Ascending Dose Study of AMG
133 in Participants With Obesity. Available at:
https://clinicaltrials.gov/ct2/show/NCT04478708. Accessed November
2022.
|
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SOURCE Amgen