MITIGATE Phase 3 Study Results Reinforce
Promise of UPLIZNA® as the First Potential
Treatment tor IgG4-RD
Phase 4 AGILE Data Support Shortening
KRYSTEXXA® Infusion Time
THOUSAND
OAKS, Calif., Nov. 14,
2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today
announced the presentation of new data across its rare disease
portfolio and pipeline at the annual American College of
Rheumatology (ACR) Convergence 2024 conference in Washington, D.C., Nov.
14-19, 2024. New data showcase reduction in disease
activity by UPLIZNA® (inebilizumab-cdon) in Immunoglobulin
G4-Related Disease (IgG4-RD) and support shorter infusion times for
KRYSTEXXA® (pegloticase) co-administered with weekly oral
methotrexate 15 mg.
"These data add to the growing body of evidence for UPLIZNA and
KRYSTEXXA and strengthen our commitment to developing new treatment
options for rare diseases like IgG4-RD and uncontrolled gout," said
Jay Bradner, M.D., executive vice
president of Research and Development and chief scientific officer
at Amgen. "Patients living with these debilitating conditions
deserve new approaches targeting the underlying causes of disease,
potentially improving outcomes and enhancing the overall treatment
experience."
Key presentations include:
A Phase 3, Randomized, Double-Blind, Multicenter,
Placebo-Controlled Study of Inebilizumab in IgG4-Related Disease
(MITIGATE): Primary Efficacy and Safety Findings
Abstract
#0775, Abstract Session: Saturday, Nov.
16 from 1:00 p.m. –
1:15 p.m. ET
MITIGATE, the first randomized, double-blind, placebo-controlled
study ever conducted in IgG4-RD, evaluated the safety and efficacy
of CD19+ B-cell depletion with UPLIZNA.
Key findings include*:
- A clinically meaningful and statistically significant 87%
reduction in the risk of IgG4-RD flare compared to placebo (Hazard
Ratio 0.13, p<0.001) during the 52-week placebo-controlled
period; seven of 68 participants receiving UPLIZNA experienced a
flare compared to 40 of 67 participants receiving placebo.
- A reduction in annualized flare rate for treated and
adjudication committee-determined flares during the
placebo-controlled period; 0.10 for participants receiving UPLIZNA
compared to 0.71 for participants receiving placebo
(p<0.001).
- 57.4% (39 of 68) of participants receiving UPLIZNA achieved
flare-free, treatment-free, complete remission at Week 52 compared
to 22.4% (15 of 67) participants receiving placebo
(p<0.001).
- 58.8% (40 of 68) of participants receiving UPLIZNA achieved
flare-free, corticosteroid-free, complete remission at Week 52
compared to 22.4% (15 of 67) participants receiving placebo
(p<0.001).
- Confirmation of the unique mechanism of action of UPLIZNA to
deliver rapid and sustained depletion of peripheral B cells leading
to lowered levels of disease biomarkers. Flares are indicative of
high disease activity.
Notably, 89.7% (61 of 68) of UPLIZNA-treated patients required
no glucocorticoid treatment for disease control during the
placebo-controlled period, compared to 37.3% (25 of 67) of patients
on placebo. After Week 8, UPLIZNA-treated patients experienced a
ten-fold reduction in total glucocorticoid use relative to
placebo.
The safety results in the placebo-controlled period were
consistent with the established safety profile of UPLIZNA. The most
common treatment-emergent adverse events included COVID-19,
lymphopenia, urinary tract infection, and headache.
The data were simultaneously published in the New England
Journal of Medicine. In August, the U.S. Food and Drug
Administration granted Breakthrough Therapy Designation for UPLIZNA
in IgG4-RD based on data from the MITIGATE study, and regulatory
filing activities are currently underway.
*All p-values follow the New England Journal of Medicine
reporting guidelines; values smaller than 0.001 are presented as
0.001.
Safety, Tolerability and Efficacy of Pegloticase Administered
with a Shorter Infusion Duration in Subjects with Uncontrolled Gout
Receiving Methotrexate: Primary Findings of the AGILE Open-label
Trial
Abstract #2012, Poster Session C: Monday, Nov. 18 from 10:30
p.m. – 12:30 p.m. ET
The AGILE trial assessed the safety, tolerability and efficacy
of KRYSTEXXA administered with a shorter infusion duration in
patients with uncontrolled gout receiving methotrexate as
co-administration.
Safety and efficacy data from the 60-minute infusion duration
cohort of the AGILE trial are similar to the MIRROR randomized
clinical trial and current administration of KRYSTEXXA with
methotrexate over at least 120 minutes.
Key findings include:
- 67.2% (78 of 116) of participants receiving a 60-minute
infusion duration of KRYSTEXXA with methotrexate achieved and
maintained a response during Month 6, defined as a urate level of
< 6mg/dL for ≥80% of the time.
- 6.0% (7 of 116) of participants receiving a 60-minute infusion
duration of KRYSTEXXA with methotrexate experienced an infusion
reaction, including anaphylaxis (1.7%; 2 of 116 participants),
based on adjudicated results.
Regulatory filings for the AGILE study findings are currently
underway.
About Uncontrolled Gout
Gout is a chronic, progressive inflammatory form of arthritis
that is caused by high urate levels in the body. Tiny needle-like
crystals can form and build up almost anywhere in the body.
Patients with uncontrolled gout continue to have high levels of
uric acid and ongoing symptoms of gout despite the use of oral
urate-lowering therapies. Uncontrolled gout is a chronic, systemic
disease, and if not addressed can have significant clinical
consequences.
About KRYSTEXXA® (pegloticase)
KRYSTEXXA is the first and only biologic approved by the FDA to
treat adults living with uncontrolled gout, a painful and
debilitating inflammatory condition with which people continue to
have abnormally high levels of uric acid and symptoms despite the
use of conventional therapies.
In 2022, the FDA approved expanding labeling to include
co-administration with the immunomodulator methotrexate, based on
results from the MIRROR randomized controlled trial, which showed
significant improvements in efficacy and safety, including a
reduction in infusion reactions.
KRYSTEXXA® (pegloticase) U.S. Indication
KRYSTEXXA is indicated for the treatment of chronic gout in
adult patients who have failed to normalize serum uric acid and
whose signs and symptoms are inadequately controlled with xanthine
oxidase inhibitors at the maximum medically appropriate dose or for
whom these drugs are contraindicated.
Limitations of Use: KRYSTEXXA is not recommended for the
treatment of asymptomatic hyperuricemia.
KRYSTEXXA U.S. Important Safety Information
WARNING: ANAPHYLAXIS AND INFUSION REACTIONS, G6PD DEFICIENCY
ASSOCIATED HEMOLYSIS AND METHEMOGLOBINEMIA
- Anaphylaxis and infusion reactions have been reported to
occur during and after administration of KRYSTEXXA.
- Anaphylaxis may occur with any infusion, including a first
infusion and generally manifests within 2 hours of the infusion.
Delayed hypersensitivity reactions have also been
reported.
- KRYSTEXXA should be administered in healthcare settings and
by healthcare providers prepared to manage anaphylaxis and infusion
reactions.
- Premedicate with antihistamines and corticosteroids and
closely monitor for anaphylaxis for an appropriate period after
administration of KRYSTEXXA.
- Monitor serum uric acid levels prior to each infusion and
discontinue treatment if levels increase to above 6 mg/dL,
particularly when 2 consecutive levels above 6 mg/dL are
observed.
- Screen patients at risk for glucose-6-phosphate
dehydrogenase (G6PD) deficiency prior to starting KRYSTEXXA.
Hemolysis and methemoglobinemia have been reported with KRYSTEXXA
in patients with G6PD deficiency. KRYSTEXXA is contraindicated in
patients with G6PD deficiency.
CONTRAINDICATIONS
- In patients with G6PD deficiency.
- In patients with history of serious hypersensitivity reactions,
including anaphylaxis, to KRYSTEXXA or any of its components.
WARNINGS AND PRECAUTIONS
Gout Flares: An increase in gout flares is
frequently observed upon initiation of anti-hyperuricemic therapy,
including KRYSTEXXA. Gout flare prophylaxis with a non-steroidal
anti-inflammatory drug (NSAID) or colchicine is recommended
starting at least 1 week before initiation of KRYSTEXXA therapy and
lasting at least 6 months, unless medically contraindicated or not
tolerated.
Congestive Heart Failure: KRYSTEXXA has not been formally
studied in patients with congestive heart failure, but some
patients in the pre-marketing placebo-controlled clinical trials
experienced exacerbation. Exercise caution in patients who have
congestive heart failure and monitor patients closely following
infusion.
ADVERSE REACTIONS
The most commonly reported adverse reactions (≥5%) are:
- KRYSTEXXA co-administration with methotrexate: gout
flares, arthralgia, COVID-19, nausea and fatigue; KRYSTEXXA alone:
gout flares, arthralgia, COVID-19, nausea, fatigue, infusion
reactions, pain in extremity, hypertension and vomiting.
- KRYSTEXXA pre-marketing placebo-controlled trials: gout
flares, infusion reactions, nausea, contusion or ecchymosis,
nasopharyngitis, constipation, chest pain, anaphylaxis and
vomiting.
Please see Full Prescribing Information,
including Boxed Warning.
About Immunoglobulin G4-related disease (IgG4-RD)
Immunoglobulin G4-related disease (IgG4-RD) is a chronic,
systemic, immune-mediated, fibroinflammatory disease which can
affect numerous and generally multiple organs of the body. It is a
progressive disease affecting new organs over time either
consecutively or simultaneously and is characterized by periods of
remission and unpredictable disease flares. IgG4-RD can cause
irreversible organ damage with or without the presence of symptoms.
Awareness of how organ damage manifests is critically important to
inform the timely diagnosis of IgG4-RD. B cells are central to the
pathogenesis of IgG4-RD. In IgG4-RD, CD19-expressing (CD19+) B
cells are thought to drive inflammatory and fibrotic processes and
interact with other immune cells that contribute to disease
activity.
The incidence is estimated at 1-5 in 100,000 although the number
of IgG4-RD patients is difficult to determine based on limited
epidemiology data. The typical age of onset of IgG4-RD is between
50 and 70 years old and, unlike many other immune-mediated
diseases, IgG4-RD is more likely to occur in men than women.
About UPLIZNA® (inebilizumab-cdon)
UPLIZNA is a humanized monoclonal antibody (mAb) that causes
targeted and sustained depletion of key cells that contribute to
underlying disease process (autoantibody-producing CD19+ B cells,
including plasmablasts and some plasma cells). After two initial
infusions, patients need one dose of UPLIZNA every six months.
UPLIZNA is currently approved for the treatment of neuromyelitis
optica spectrum disorder (NMOSD) in adult patients who are
anti-aquaporin-4 (AQP4) antibody positive in the United States and other countries around
the world.
UPLIZNA® (inebilizumab-cdon) U.S.
INDICATION
UPLIZNA is indicated for the treatment of neuromyelitis optica
spectrum disorder (NMOSD) in adult patients who are
anti-aquaporin-4 (AQP4) antibody positive.
IMPORTANT SAFETY INFORMATION
UPLIZNA is contraindicated in patients with:
- A history of life-threatening infusion reaction to UPLIZNA
- Active hepatitis B infection
- Active or untreated latent tuberculosis
WARNINGS AND PRECAUTIONS
Infusion Reactions: UPLIZNA can cause infusion reactions,
which can include headache, nausea, somnolence, dyspnea, fever,
myalgia, rash, or other symptoms. Infusion reactions were most
common with the first infusion but were also observed during
subsequent infusions. Administer pre-medication with a
corticosteroid, an antihistamine, and an anti-pyretic.
Infections: The most common infections reported by
UPLIZNA-treated patients in the randomized and open-label periods
included urinary tract infection (20%), nasopharyngitis (13%),
upper respiratory tract infection (8%), and influenza (7%). Delay
UPLIZNA administration in patients with an active infection until
the infection is resolved.
Increased immunosuppressive effects are possible if combining
UPLIZNA with another immunosuppressive therapy.
The risk of Hepatitis B Virus (HBV) reactivation has been
observed with other B-cell-depleting antibodies. Perform HBV
screening in all patients before initiation of treatment with
UPLIZNA. Do not administer to patients with active hepatitis.
Although no confirmed cases of Progressive Multifocal
Leukoencephalopathy (PML) were identified in UPLIZNA clinical
trials, JC virus infection resulting in PML has been observed in
patients treated with other B-cell-depleting antibodies and other
therapies that affect immune competence. At the first sign or
symptom suggestive of PML, withhold UPLIZNA and perform an
appropriate diagnostic evaluation.
Patients should be evaluated for tuberculosis risk factors and
tested for latent infection prior to initiating UPLIZNA.
Vaccination with live-attenuated or live vaccines is not
recommended during treatment and after discontinuation, until
B-cell repletion.
Reduction in Immunoglobulins: There may be a progressive
and prolonged hypogammaglobulinemia or decline in the levels of
total and individual immunoglobulins such as immunoglobulins G and
M (IgG and IgM) with continued UPLIZNA treatment. Monitor the level
of immunoglobulins at the beginning, during, and after
discontinuation of treatment with UPLIZNA until B-cell repletion
especially in patients with opportunistic or recurrent
infections.
Fetal Risk: May cause fetal harm based on animal
data. Advise females of reproductive potential of the potential
risk to a fetus and to use an effective method of contraception
during treatment and for 6 months after stopping UPLIZNA.
Adverse Reactions: The most common adverse reactions (at
least 10% of patients treated with UPLIZNA and greater than
placebo) were urinary tract infection and arthralgia.
For additional information on UPLIZNA, please see the Full
Prescribing Information at www.UPLIZNA.com.
About Amgen
Amgen discovers, develops, manufactures, and delivers innovative
medicines to help millions of patients in their fight against some
of the world's toughest diseases. More than 40 years ago, Amgen
helped to establish the biotechnology industry and remains on the
cutting-edge of innovation, using technology and human genetic data
to push beyond what's known today. Amgen is advancing a broad and
deep pipeline that builds on its existing portfolio of medicines to
treat cancer, heart disease, osteoporosis, inflammatory diseases
and rare diseases.
In 2024, Amgen was named one of the "World's Most Innovative
Companies" by Fast Company and one of "America's Best Large
Employers" by Forbes, among other external recognitions. Amgen is
one of the 30 companies that comprise the Dow Jones Industrial
Average®, and it is also part of the Nasdaq-100
Index®, which includes the largest and most innovative
non-financial companies listed on the Nasdaq Stock Market based on
market capitalization.
For more information, visit Amgen.com and follow Amgen on
X, LinkedIn, Instagram, TikTok, YouTube and Threads.
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. or Kyowa Kirin Co., Ltd.), the performance
of Otezla® (apremilast) (including anticipated Otezla sales growth
and the timing of non-GAAP EPS accretion), our acquisitions of
Teneobio, Inc., ChemoCentryx, Inc., or Horizon Therapeutics plc
(including the prospective performance and outlook of Horizon's
business, performance and opportunities, any potential strategic
benefits, synergies or opportunities expected as a result of such
acquisition, and any projected impacts from the Horizon acquisition
on our acquisition-related expenses going forward), 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
on our business, outcomes, progress, 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. There can be no
guarantee that we will be able to realize any of the strategic
benefits, synergies or opportunities arising from the Horizon
acquisition, and such benefits, synergies or opportunities may take
longer to realize than expected. We may not be able to successfully
integrate Horizon, and such integration may take longer, be more
difficult or cost more than expected. A breakdown, cyberattack or
information security breach of our information technology systems
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. Our business and operations may be
negatively affected by the failure, or perceived failure, of
achieving our environmental, social and governance objectives. The
effects of global climate change and related natural disasters
could negatively affect our business and operations. 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.
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
Madison Howard, 773-635-4910
(media)
Elissa Snook, 609-251-1407
(media)
Justin Claeys, 805-313-9775
(investors)
View original content to download
multimedia:https://www.prnewswire.com/news-releases/amgen-presents-new-data-across-rare-inflammatory-diseases-at-acr-2024-302306359.html
SOURCE Amgen