THOUSAND OAKS, Calif. and
TOKYO, Oct. 2, 2021
/PRNewswire/ -- Amgen (NASDAQ: AMGN) and Kyowa Kirin Co., Ltd.
(TSE:4151) today announced that positive data from a Phase 2 study
of AMG 451/KHK4083 were presented at the European Academy of
Dermatology and Venereology 30th Virtual Congress on
Oct. 2, 2021. AMG 451/KHK4083 is a
potential first-in-class anti-OX40 fully human monoclonal antibody
in development for the treatment of moderate-to-severe atopic
dermatitis.
The Phase 2, multicenter, randomized, double-blind,
placebo-controlled trial investigated the efficacy and safety of
AMG 451/KHK4083 in adults with moderate-to-severe atopic dermatitis
who were not adequately controlled with topical agents. The study
met the primary objective, showing statistically greater
improvements from baseline in Eczema Area and Severity Index (EASI)
score at 16 weeks with all four subcutaneous doses of AMG
451/KHK4083 compared with placebo (600 mg every two weeks (Q2W) =
-57.4%; 600 mg Q4W = -49.7%; 300 mg Q2W = -61.1%; 150 mg Q4W =
-48.3% vs. placebo = -15%; P<0.001).
All treatment groups of patients receiving AMG 451/KHK4083
generally achieved improvements compared to placebo at week 16 for
key secondary endpoints, such as achieving at least a 75% reduction
from baseline in EASI score (EASI-75), an Investigator Global
Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at
least 2-point reduction from baseline (IGA 0/1) and at least a
4-point reduction from baseline in pruritus Numerical Rating Scale
(NRS) score (PNRS-4). Efficacy measures continued to improve after
week 16 for all AMG 451/KHK4083 doses.
The most commonly reported adverse events that occurred in at
least 5% of patients were pyrexia, nasopharyngitis, worsening of
atopic dermatitis and chills. The events of pyrexia and chills were
mild to moderate in intensity and did not lead to treatment
discontinuations.
"The Phase 2 results are both positive and exciting. They show
improvement across all 4 dose groups compared to placebo, and
highlight the potential of OX40 antagonism to help patients," said
the lead investigator of this study, Dr. Emma Guttman-Yassky, MD./PhD., system chair for
the Department of Dermatology and Waldman Professor of Dermatology
and Immunology, Icahn School of Medicine at Mount Sinai and
Director of the Center for Excellence in Eczema, and the Laboratory
of Inflammatory Skin Diseases at Mount Sinai. "I hope that future
clinical development data will further elucidate the significance
and potential of AMG 451/KHK4083 in the treatment of
moderate-to-severe atopic dermatitis."
"We are very pleased to present data from our Phase 2 study
assessing the efficacy and safety of AMG 451/KHK4083 in chronic,
recurrent, moderate-to-severe atopic dermatitis at the EADV
congress," said Yoshifumi Torii,
Ph.D., executive officer, vice president, head of R&D Division
of Kyowa Kirin. "The results show inhibition and deletion of the
OX40-expressing cells may provide an important new approach to
treating moderate-to-severe atopic dermatitis, with the potential
to help patients maintain responses."
"Atopic dermatitis affects nearly 30 million people a year and
is known to have an extremely negative impact on patients' lives,"
said David M. Reese, M.D., executive
vice president of Research and Development at Amgen. "These data
provide strong evidence of the potential of AMG 451/KHK4083 for
patients, and we look forward to studying this treatment further in
Phase 3 clinical trials, which we expect to begin in the first half
of 2022."
About the AMG 451/KHK4083 Phase 2 Study
The Phase 2,
multicenter, randomized, double-blind, placebo-controlled trial
(NCT03703102) investigated the efficacy and safety of AMG
451/KHK4083 in adults with moderate-to-severe atopic dermatitis who
were not adequately controlled with topical agents. The study
randomized 274 patients in the U.S., Japan, Canada
and Germany across four
dose-ranging active treatment groups, which received subcutaneous
AMG 451/KHK4083 (600mg Q2W, 600mg Q4W, 300mg Q2W, 150mg Q4W), and a
comparator placebo arm.
The primary endpoint was percentage change from baseline in EASI
score at week 16. Additional endpoints include achievement of ≥75%
reduction (improvement) from baseline in EASI score, IGA score of 0
(clear) or 1 (almost clear) with ≥ 2 points reduction from
baseline, and ≥ 4 points reduction from baseline in the pruritus
numeric rating scale (NRS) score. Patients in the study were
followed up to week 56.
The presentation slides are available on the EADV website:
https://www.eadvcongress2021.org/.
Dr. Emma Guttman-Yassky is the
lead investigator of the study and a paid consultant for the AMG
451/KHK4083 development by Kyowa Kirin.
About Atopic Dermatitis
Atopic dermatitis is a chronic
inflammatory disease that causes excessively dry, itchy skin that
can be painful. Repeated scratching can cause the skin to thicken,
harden or become vulnerable to infection. Atopic dermatitis is the
most common form of eczema – affecting 1-3% of adults worldwide –
and the prevalence is increasing. The disease typically manifests
in childhood followed by other allergy symptoms.
About AMG 451/KHK4083
AMG 451/KHK4083 is an anti-OX40
fully human monoclonal antibody engineered with Kyowa Kirin's
patented POTELLIGENT® defucosylation technology to
enhance its antibody-dependent cellular cytotoxicity (ADCC)
activity. The initial AMG 451/KHK4083 antibody was discovered in
collaboration between Kyowa Kirin US Research and La Jolla
Institute for Immunology.
AMG 451/KHK4083 targets and inhibits the activity of the OX40
receptor expressed on the surface of activated effector T-cells,
and has been shown to enhance the depletion of activated OX40+
T-cells by ADCC. It has been reported that effector T-cells
expressing OX40 are present in the lesions of patients with atopic
dermatitis and are critical in the disease pathophysiology.
Amgen and Kyowa Kirin Collaboration
On June 1, 2021, Amgen and Kyowa Kirin entered into
an agreement to jointly develop and commercialize AMG 451/KHK4083.
Under the terms of the agreement, Amgen will lead the development,
manufacturing, and commercialization for AMG 451/KHK4083 for all
markets globally, except Japan,
where Kyowa Kirin will retain all rights. If approved, the
companies will co-promote the asset in the United States and Kyowa Kirin has opt-in
rights to co-promote in certain other markets including
Europe and Asia.
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.
For more information, visit www.amgen.com and follow us on
www.twitter.com/amgen.
About Kyowa Kirin
Kyowa Kirin strives to create and
deliver novel medicines with life-changing value. As a Japan-based Global Specialty Pharmaceutical
Company with a more than 70-year heritage, we apply cutting-edge
science including expertise in antibody research and engineering,
to address the needs of patients and society across multiple
therapeutic areas including Nephrology, Oncology,
Immunology/Allergy and Neurology. Across our four regions –
Japan, Asia Pacific, North
America and EMEA/International – we focus on our purpose, to
make people smile, and are united by our shared values of
commitment to life, teamwork/Wa, innovation, and integrity. You can
learn more about the business of Kyowa Kirin at:
https://www.kyowakirin.com/.
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, 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
practices, reimbursement activities and outcomes, effects of
pandemics or other widespread health problems such as the ongoing
COVID-19 pandemic on our business, outcomes, progress, or effects
relating to studies of Otezla as a potential treatment for
COVID-19, 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
indications for existing products cannot be guaranteed and movement
from concept to product is uncertain; consequently, there can be no
guarantee that any particular product candidate or development of a
new indication for an existing product will be successful and
become a commercial product. Further, preclinical results do not
guarantee safe and effective performance of product candidates in
humans. The complexity of the human body cannot be perfectly, or
sometimes, even adequately modeled by computer or cell culture
systems or animal models. The length of time that it takes for us
to complete clinical trials and obtain regulatory approval for
product marketing has in the past varied and we expect similar
variability in the future. Even when clinical trials are
successful, regulatory authorities may question the sufficiency for
approval of the trial endpoints we have selected. We develop
product candidates internally and through licensing collaborations,
partnerships and joint ventures. Product candidates that are
derived from relationships may be subject to disputes between the
parties or may prove to be not as effective or as safe as we may
have believed at the time of entering into such relationship. Also,
we or others could identify safety, side effects or manufacturing
problems with our products, including our devices, after they are
on the market.
Our results may be affected by our ability to successfully
market both new and existing products domestically and
internationally, clinical and regulatory developments involving
current and future products, sales growth of recently launched
products, competition from other products including biosimilars,
difficulties or delays in manufacturing our products and global
economic conditions. In addition, sales of our products are
affected by pricing pressure, political and public scrutiny and
reimbursement policies imposed by third-party payers, including
governments, private insurance plans and managed care providers and
may be affected by regulatory, clinical and guideline developments
and domestic and international trends toward managed care and
healthcare cost containment. Furthermore, our research, testing,
pricing, marketing and other operations are subject to extensive
regulation by domestic and foreign government regulatory
authorities. Our business may be impacted by government
investigations, litigation and product liability claims. In
addition, our business may be impacted by the adoption of new tax
legislation or exposure to additional tax liabilities. If we fail
to meet the compliance obligations in the corporate integrity
agreement between us and the U.S. government, we could become
subject to significant sanctions. Further, while we routinely
obtain patents for our products and technology, the protection
offered by our patents and patent applications may be challenged,
invalidated or circumvented by our competitors, or we may fail to
prevail in present and future intellectual property litigation. We
perform a substantial amount of our commercial manufacturing
activities at a few key facilities, including in Puerto Rico, and also depend on third parties
for a portion of our manufacturing activities, and limits on supply
may constrain sales of certain of our current products and product
candidate development. An outbreak of disease or similar public
health threat, such as COVID-19, and the public and governmental
effort to mitigate against the spread of such disease, could have a
significant adverse effect on the supply of materials for our
manufacturing activities, the distribution of our products, the
commercialization of our product candidates, and our clinical trial
operations, and any such events may have a material adverse effect
on our product development, product sales, business and results of
operations. We rely on collaborations with third parties for the
development of some of our product candidates and for the
commercialization and sales of some of our commercial products. In
addition, we compete with other companies with respect to many of
our marketed products as well as for the discovery and development
of new products. Further, some raw materials, medical devices and
component parts for our products are supplied by sole third-party
suppliers. Certain of our distributors, customers and payers have
substantial purchasing leverage in their dealings with us. The
discovery of significant problems with a product similar to one of
our products that implicate an entire class of products could have
a material adverse effect on sales of the affected products and on
our business and results of operations. Our efforts to collaborate
with or acquire other companies, products or technology, and to
integrate the operations of companies or to support the products or
technology we have acquired, may not be successful. A breakdown,
cyberattack or information security breach could compromise the
confidentiality, integrity and availability of our systems and our
data. Our stock price is volatile and may be affected by a number
of events. Global economic conditions may magnify certain risks
that affect our business. Our business performance could affect or
limit the ability of our Board of Directors to declare a dividend
or our ability to pay a dividend or repurchase our common stock. We
may not be able to access the capital and credit markets on terms
that are favorable to us, or at all.
The scientific information discussed in this news release
related to our product candidates is preliminary and investigative.
Such product candidates are not approved by the U.S. Food and Drug
Administration, and no conclusions can or should be drawn regarding
the safety or effectiveness of the product candidates. Further, any
scientific information discussed in this news release relating to
new indications for our products is preliminary and investigative
and is not part of the labeling approved by the U.S. Food and Drug
Administration for the products. The products are not approved for
the investigational use(s) discussed in this news release, and no
conclusions can or should be drawn regarding the safety or
effectiveness of the products for these uses.
CONTACT:
Amgen, Thousand Oaks
Michael Strapazon, 805-313-5553
(Media)
Trish Rowland, 805-447-5631
(Media)
Arvind Sood, 805-447-1060
(Investors)
Kyowa Kirin, Tokyo
Hiroki Nakamura (Global,
Japan), +81-3-5205-7205
Lauren Walrath (North America), +1-646-526-4454
Stacey Minton (EMEA), +44 (0) 7769
65607
View original content to download
multimedia:https://www.prnewswire.com/news-releases/amgen-and-kyowa-kirin-present-positive-late-breaking-data-from-phase-2-study-of-amg-451khk4083-in-adult-patients-with-moderate-to-severe-atopic-dermatitis-at-eadv-congress-301391185.html
SOURCE Amgen