Data Show a Statistically Significant 87%
Reduction in IgG4-RD Flares, With Primary and All Key Secondary
Endpoints Met
First Randomized, Placebo-Controlled Trial to
Demonstrate Benefit in IgG4-RD
THOUSAND
OAKS, Calif., June 5, 2024
/PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced positive
topline results from its randomized, double-blind, multicenter,
placebo-controlled Phase 3 clinical trial (NCT04540497) evaluating
the efficacy and safety of UPLIZNA® (inebilizumab-cdon)
for the treatment of Immunoglobulin G4-related disease
(IgG4-RD).
The trial met its primary endpoint, showing a statistically
significant 87% reduction in the risk of IgG4-RD flare compared to
placebo (Hazard Ratio 0.13, p<0.0001) during the 52-week
placebo-controlled period. All key secondary endpoints were also
met, which were annualized flare rate; flare-free, treatment-free
complete remission; and flare-free, corticosteroid-free complete
remission. No new safety signals were identified. The overall
safety results during the placebo-controlled period of the trial
were consistent with the known safety profile of UPLIZNA. Full data
from the trial will be presented at a future medical meeting.
"MITIGATE is a landmark study with results that demonstrate an
important advance in the treatment of patients with IgG4-RD, a
devastating and rare disease that currently has no approved
therapy," said Jay Bradner, M.D.,
executive vice president, Research and Development, and chief
scientific officer at Amgen. "We are grateful for the partnership
with patients, clinicians and patient advocacy groups critical to a
successful study, and we look forward to bringing this therapy to
those living with IgG4-RD."
MITIGATE was conducted at 80 sites in 22 countries. It is the
first placebo-controlled trial providing class 1 evidence for
treating IgG4-RD, a chronic, systemic, immune-mediated,
fibroinflammatory disease that can affect almost any organ in the
body, often involving multiple organs at a time, and can result in
irreversible organ damage. The novel, steroid-sparing study design
paves the way for a reduced toxicity treatment approach.
"IgG4-RD is a devastating, chronic, immune-mediated disease that
has just begun to be fully understood over the last few decades,"
said John Stone, M.D., M.P.H.,
principal investigator, and a professor of medicine at Harvard Medical School and the Edward A. Fox Chair
in Medicine at the Massachusetts General Hospital. "These data mark
a major milestone for the IgG4-RD community and provide substantial
insight into not only how inebilizumab can help manage IgG4-RD, but
also key insights into the nature of this condition."
UPLIZNA is currently approved for Neuromyelitis Optica Spectrum
Disorder (NMOSD) by several regulatory bodies, including the U.S.
Food and Drug Administration, the European Medicines Agency, Health
Canada and the Brazilian Health Regulatory Agency (ANVISA),
among others.
Based on the MITIGATE primary analysis
results, Amgen is planning to file for approval in the
U.S. followed by other key markets.
The trial was conducted with the support of Mitsubishi Tanabe
Pharma and Hansoh Pharma. Mitsubishi Tanabe Pharma holds marketing
authorization for UPLIZNA in Japan, Thailand, South
Korea, Indonesia,
Vietnam, Malaysia, Philippines, Singapore, and Taiwan. Hansoh Pharma is the exclusive
licensee, local regulatory and commercial agent for China's mainland, Hong Kong, and Macau.
About the MITIGATE Trial
MITIGATE is a randomized, double-blind, placebo-controlled,
parallel-group, multicenter trial designed to evaluate the efficacy
and safety of UPLIZNA compared to placebo in reducing the risk of
flares in adults with IgG4-RD.
The trial enrolled 135 adults with IgG4-RD who met a robust
assessment and central eligibility review. Eligibility criteria
included multi-organ disease history and active disease being
treated with glucocorticoids at the time of screening to ensure
enrollment of a patient population at risk of flares for the
primary endpoint.
After a screening period of up to 28 days, patients were
randomized (1:1) to receive 300 mg intravenous (IV) UPLIZNA or
placebo on Days 1, 15, and Week 26 after premedication, and
followed for the 52-week randomized control period.
The primary endpoint was time to first treated and adjudicated
IgG4-RD flare. The three key secondary endpoints were annualized
flare rate; flare-free, treatment-free complete remission; and
flare-free, corticosteroid-free complete remission. The MITIGATE
trial also includes an optional 3-year open-label treatment period
and a safety follow-up period after UPLIZNA discontinuation of up
to two years.
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.1,2 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.3,4 IgG4-RD can cause irreversible organ damage
with or without the presence of symptoms.5 B cells are
central to the pathogenesis of IgG4-RD.1 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.1,2,7
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.3 The typical age of onset of
IgG4-RD is between 50 and 70 years old4 and, unlike many
other immune-mediated diseases, IgG4-RD is more likely to occur in
men than women.6
About UPLIZNA® (inebilizumab-cdon)
INDICATION
UPLIZNA® (inebilizumab-cdon) 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
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is one of the 30 companies that comprise the Dow Jones Industrial
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CONTACT: Amgen, Thousand
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References
- Perugino, C. A., & Stone, J. H. (2020). IgG4-related
disease: an update on pathophysiology and implications for clinical
care. Nature Reviews Rheumatology, 16(12), 702–714.
- Stone, J. H., Zen, Y., & Deshpande, V. (2012). IgG4-Related
Disease. New England Journal of Medicine, 366(6), 539–551.
- Floreani, A., Okazaki, K., Uchida, K., & Gershwin, M. E.
(2021). IgG4-related disease: Changing epidemiology and new
thoughts on a multisystem disease. Journal of Translational
Autoimmunity, 4, 100074.
- Wallace, Z. S., Mattoo, H., Mahajan, V. S., Kulikova, M., Lu,
L., Deshpande, V., Choi, H. K., Pillai, S., & Stone, J. H.
(2016). Predictors of disease relapse in IgG4-related disease
following rituximab. Rheumatology, 55(6), 1000–1008.
- Zhang, W., & Stone, J. H. (2019). Management of
IgG4-related disease. The Lancet Rheumatology, 1(1), e55–e65.
- Brito-Zerón, P., Bosch, X., Gandía, M., Soto Cárdenas, M.-J. ,
Ramos-Casals, M., & Stone, J. H. (2017, January
1). Chapter 22 (pages 399-410) - IgG4-Related Disease:
Gastrointestinal Involvement (M. Ramos-Casals, M. Khamashta,
P. Britó-Zeron, F. Atzeni, & J. R. Teixidor, Eds.).
ScienceDirect; Elsevier.
- Wolfson, A. R., & Hamilos, D. L. (2017). Recent advances in
understanding and managing IgG4-related disease. F1000Research, 6,
185.
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