- Findings from head-to-head Early AMPLE
study are consistent with earlier studies, adding to body of
research showing differences between mechanisms of biologic
therapies
- Results suggest that a genetic marker
linked to autoantibody production and a more severe RA disease
course – “Shared Epitope” – can help identify patients who may
receive enhanced benefit from treatment with ORENCIA
- Late-breaking oral presentation is one
of 27 Bristol-Myers Squibb sponsored abstracts featured at the
Annual European Congress of Rheumatology (EULAR 2019)
Bristol-Myers Squibb Company (NYSE:BMY) today announced data
from a Phase IV mechanistic study exploring differences in the
cellular and molecular mechanisms by which ORENCIA® (abatacept) and
another treatment, adalimumab, interfere with disease progression
in moderate-to-severe early rheumatoid arthritis (RA) patients
seropositive for certain autoantibodies. These results, which are
from a prospective analysis of the Early AMPLE
head-to-head trial, are featured in a
late-breaking oral presentation at the Annual European
Congress of Rheumatology (EULAR 2019), June 12-15 in
Madrid.
Among 80 adult patients with early (≤ 12 months from symptom
onset) moderate-to-severe RA who had never been treated with a
biologic medication and tested positive for autoantibodies called
anti-citrullinated protein antibody (ACPA) and rheumatoid
factor (RF), numerically higher efficacy responses were seen with
ORENCIA at week 24. ACR 20/50/70 responses with ORENCIA were 83, 70
and 48 respectively; ACR 20/50/70 scores for adalimumab were 63, 45
and 30, respectively. Higher responses were observed in patients
with a well-known genetic marker of RA prognosis called the
“Shared Epitope” (SE). In SE+ patients, numerically greater
efficacy was observed with ORENCIA [estimate of difference in the
SE+ group for ACR 20 was 28.6 (95% CI 4.6, 51.7); for ACR 50 was
31.5 (95% CI 6.8, 54.5); for ACR 70, 27.6 (95% CI 1.4, 50.5); for
DAS28-CRP remission (<2.6), 27.4 (95% CI 1.2, 49.8)]. Patients
in both arms of the study were also treated with stable, oral
methotrexate (MTX) weekly.
Rheumatoid factor and ACPA are biomarkers associated with a more
severe disease course in RA. The HLA-DRB1 allele, which codes for
SE, provides instructions for making a protein that plays a key
role in helping the immune system distinguish one’s own proteins
from those of harmful invaders, such as bacteria and viruses.
Shared Epitope has been shown to be strongly associated with RA,
and is thought to be involved with the continuous activation of
immune cells, called T cells, that characterizes RA. Shared Epitope
is present in 70-80 percent of RA patients positive for ACPA.
“The Early AMPLE results are consistent with previous abatacept
research in patients who test positive for
anti-citrullinated protein antibody, and offer important
insights into the underlying genetic mechanisms at work in these
patients,” said Vivian P. Bykerk, BSc, MD, FRCPC, rheumatologist at
Hospital for Special Surgery. “This research advances our
understanding of these mechanisms and the value of the
applicability of precision medicine for patients with highly
active, progressive rheumatoid arthritis.”
Similar numbers of related adverse events (ORENCIA: 12 [30%];
adalimumab: 11 [27.5%]) and related serious adverse events
(ORENCIA: 0; adalimumab: 1 [2.5%]) were observed in the two
treatment arms. The overall safety profile of ORENCIA was
consistent with prior studies, with no new safety signals
identified.
“Investigating the impact of biomarkers is central to our goal
of informing better, more personalized approaches in
immune-mediated diseases where treatment options are limited
or improvements are needed,” said Dr. Brian Gavin, development
lead, ORENCIA, Bristol-Myers Squibb. “The results from Early AMPLE
are exciting because they support the clinical profile of ORENCIA
as a first-line treatment option for patients with
moderate-to-severe RA, and further our understanding
of which patients may benefit most from ORENCIA therapy.”
At the Annual European Congress of Rheumatology (EULAR 2019),
Bristol-Myers Squibb sponsored a total of 27 abstracts.
These include clinical and real-world results on ORENCIA
that support our focuses on furthering precision medicine in RA and
addressing unmet patient needs in moderate-to-severe juvenile
idiopathic arthritis. Findings on new modes of action being
explored as part of Bristol-Myers Squibb’s early
Immunoscience program also will be shared. A full list of abstract
titles and authors can be accessed online here.
About the Early AMPLE
Study
Early AMPLE, a phase IV randomized, head-to-head, single-blinded
study of 24 weeks duration with multiple exploratory endpoints
(changes to autoantibody levels, changes to cytokines, changes to
percentages of immune cell subsets, and changes to activation
states of immune cell subsets), compared the efficacy of the
subcutaneous (SC) formulation of ORENCIA versus adalimumab on a
background of MTX in adult, biologic-naïve patients with
moderate-to-severe RA.
In this prospective analysis, adults with early (≤ 12 months
from symptom onset), moderate-to-severe RA (ACR/EULAR
2010 criteria) seropositive for ACPA and RF, were randomized 1:1 to
SC ORENCIA 125 mg weekly or SC adalimumab 40 mg every 2 weeks (both
with stable, oral MTX weekly) for 24 weeks. Patients were grouped
by SE status (+/−) based on HLA-DRB1 genotype (−: no SE allele; +:
≥ 1 SE allele). Safety was analyzed throughout the trial and up to
8 weeks post last study drug dose. Clinical efficacy was assessed
at week 24 to determine the proportion of ACR20/50/70 responders in
the ORENCIA versus adalimumab arms, and the adjusted mean changes
from baseline in DAS28 (CRP), SDAI and CDAI. Treatment differences
between ORENCIA and adalimumab in SE+ and SE– pts were assessed for
ACR20/50/70 responders and DAS28 (CRP) remission at week 24.
Eighty patients were treated: 40 ORENCIA (9 SE−, 30 SE+, 1 SE
unknown) and 40 adalimumab (9 SE−, 31 SE+). Baseline
characteristics were balanced. Mean (SD) age, disease duration and
DAS28 (CRP) were 46.0 (14.4) years, 5.5 (2.6) months and 5.2 (1.1),
respectively; 75% were female.
About Rheumatoid
Arthritis
Rheumatoid arthritis (RA) is a destructive autoimmune disease
characterized by inflammation in the lining of joints (or
synovium), causing joint damage with chronic pain, stiffness, and
swelling. Rheumatoid arthritis causes limited range of motion and
decreased joint function. The condition is more common in women
than in men, who account for 75 percent of patients diagnosed with
RA.
About ORENCIA
ORENCIA® is an immunomodulator that disrupts the continuous
cycle of T-cell activation that characterizes RA.
U.S. Indications/Usage and Important Safety Information for
ORENCIA® (abatacept)
Indication and Usage
Adult Rheumatoid Arthritis (RA): ORENCIA® (abatacept) is
indicated for reducing signs and symptoms, inducing major clinical
response, inhibiting the progression of structural damage, and
improving physical function in adult patients with moderately to
severely active RA. ORENCIA may be used as monotherapy or
concomitantly with disease-modifying, anti-rheumatic drugs (DMARDs)
other than tumor necrosis factor (TNF) antagonists.
Juvenile Idiopathic Arthritis (JIA): ORENCIA® (abatacept)
is indicated for reducing signs and symptoms in patients 2 years of
age and older with moderately to severely active polyarticular JIA.
ORENCIA may be used as monotherapy or concomitantly with
methotrexate (MTX).
Adult Psoriatic Arthritis (PsA): ORENCIA® (abatacept) is
indicated for the treatment of adult patients with active PsA.
Important Limitations of Use: ORENCIA should not be
administered concomitantly with TNF antagonists, and is not
recommended for use concomitantly with other biologic RA therapy,
such as anakinra.
Important Safety Information for
ORENCIA® (abatacept)
Concomitant Use with TNF Antagonists: Concurrent therapy
with ORENCIA and a TNF antagonist is not recommended. In controlled
clinical trials, adult RA patients receiving concomitant
intravenous ORENCIA and TNF antagonist therapy experienced more
infections (63%) and serious infections (4.4%) compared to patients
treated with only TNF antagonists (43% and 0.8%, respectively),
without an important enhancement of efficacy.
Hypersensitivity: Anaphylaxis or anaphylactoid reactions
can occur during or after an infusion and can be life-threatening.
There were 2 cases (<0.1%; n=2688) of anaphylaxis or
anaphylactoid reactions in clinical trials with adult RA patients
treated with intravenous ORENCIA. Other reactions potentially
associated with drug hypersensitivity, such as hypotension,
urticaria, and dyspnea, each occurred in <0.9% of patients.
There was one case of a hypersensitivity reaction with ORENCIA in
JIA clinical trials (0.5%; n=190). In postmarketing experience, a
case of fatal anaphylaxis following the first infusion of ORENCIA
was reported. Appropriate medical support measures for treating
hypersensitivity reactions should be available for immediate use.
If an anaphylactic or other serious allergic reaction occurs,
administration of ORENCIA should be stopped immediately and
permanently discontinued, with appropriate therapy instituted.
Infections: Serious infections, including sepsis and
pneumonia, have been reported in patients receiving ORENCIA. Some
of these infections have been fatal. Many of the serious infections
have occurred in patients on concomitant immunosuppressive therapy
which, in addition to their underlying disease, could further
predispose them to infection. Caution should be exercised in
patients with a history of infection or underlying conditions which
may predispose them to infections. Treatment with ORENCIA should be
discontinued if a patient develops a serious infection. Patients
should be screened for tuberculosis and viral hepatitis in
accordance with published guidelines, and if positive, treated
according to standard medical practice prior to therapy with
ORENCIA.
Immunizations: Live vaccines should not be given
concurrently with ORENCIA or within 3 months of its
discontinuation. The efficacy of vaccination in patients receiving
ORENCIA is not known. ORENCIA may blunt the effectiveness of some
immunizations. It is recommended that JIA patients be brought up to
date with all immunizations in agreement with current immunization
guidelines prior to initiating therapy with ORENCIA.
Use in Patients with Chronic Obstructive Pulmonary Disease
(COPD): Adult COPD patients treated with ORENCIA developed
adverse events more frequently than those treated with placebo,
including COPD exacerbations, cough, rhonchi, and dyspnea. In adult
RA studies, 97% of COPD patients treated with ORENCIA developed
adverse reactions versus 88% treated with placebo and respiratory
disorders occurred more frequently in patients treated with ORENCIA
compared to those on placebo (43% vs 24%, respectively), including
COPD exacerbation, cough, rhonchi, and dyspnea. A greater
percentage of adult RA patients treated with ORENCIA developed a
serious adverse event compared to those on placebo (27% vs 6%),
including COPD exacerbation [3 of 37 patients (8%)] and pneumonia
[1 of 37 patients (3%)]. Use of ORENCIA in patients with RA and
COPD should be undertaken with caution, and such patients monitored
for worsening of their respiratory status.
Blood Glucose Testing: ORENCIA for intravenous
administration contains maltose, which may result in falsely
elevated blood glucose readings on the day of infusion when using
blood glucose monitors with test strips utilizing glucose
dehydrogenase pyrroloquinoline quinone (GDH-PQQ). Consider using
monitors and advising patients to use monitors that do not react
with maltose, such as those based on glucose dehydrogenase nicotine
adenine dinucleotide (GDH-NAD), glucose oxidase or glucose
hexokinase test methods. ORENCIA for subcutaneous (SC)
administration does not contain maltose; therefore, patients do not
need to alter their glucose monitoring.
Pregnancy: There are no adequate and well-controlled
studies of ORENCIA use in pregnant women and the data with ORENCIA
use in pregnant women are insufficient to inform on drug-associated
risk. A pregnancy registry has been established to monitor
pregnancy outcomes in women exposed to ORENCIA during pregnancy.
Healthcare professionals are encouraged to register patients by
calling 1-877-311-8972.
Lactation: There is no information regarding the presence
of abatacept in human milk, the effects on the breastfed infant, or
the effects on milk production. However, abatacept was present in
the milk of lactating rats dosed with abatacept.
Most Serious Adverse Reactions: Serious infections (3%
ORENCIA vs 1.9% placebo) and malignancies (1.3% ORENCIA vs 1.1%
placebo).
Malignancies: The overall frequency of malignancies was
similar between adult RA patients treated with ORENCIA or placebo.
However, more cases of lung cancer were observed in RA patients
treated with ORENCIA (0.2%) than those on placebo (0%). A higher
rate of lymphoma was seen compared to the general population;
however, patients with RA, particularly those with highly active
disease, are at a higher risk for the development of lymphoma. The
potential role of ORENCIA in the development of malignancies in
humans is unknown.
Most Frequent Adverse Events (≥10%): Headache, upper
respiratory tract infection, nasopharyngitis, and nausea were the
most commonly reported adverse events in the adult RA clinical
studies. Other events reported in ≥5% of JIA patients were
diarrhea, cough, pyrexia, and abdominal pain. In general, the
adverse events in JIA and adult PsA patients were similar in
frequency and type to those seen in adult RA patients.
Note concerning ORENCIA administration options:
Intravenous dosing has not been studied in patients younger than 6
years of age. The safety and efficacy of ORENCIA ClickJect™
Autoinjector for subcutaneous injection has not been studied in
patients under 18 years of age.
Please see Full Prescribing Information
at http://packageinserts.bms.com/pi/pi_orencia.pdf.
ORENCIA® (abatacept) is a registered trademark of
Bristol-Myers Squibb Company.
About Bristol-Myers Squibb
Immunoscience
With a robust pipeline of immunomodulatory therapies,
Bristol-Myers Squibb is committed to the discovery and
development of transformational medicines that could lead to
long-term remission in patients with immune-mediated diseases. As
we discover more about the immune system in such diseases with
substantial unmet medical needs, the potential for developing novel
therapies that target specific pathways in the immune system
continues to drive our research efforts.
About Bristol-Myers
Squibb
Bristol-Myers Squibb is a global biopharmaceutical
company whose mission is to discover, develop and deliver
innovative medicines that help patients prevail over serious
diseases. For more information about Bristol-Myers Squibb,
visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and
Facebook.
Bristol-Myers Squibb Forward-Looking
Statement
This press release contains "forward-looking statements" within
the meaning of the Private Securities Litigation Reform Act of 1995
regarding, among other things, the research, development and
commercialization of pharmaceutical products. All statements that
are not statements of historical facts are, or may be deemed to be,
forward-looking statements. Such forward-looking statements are
based on historical performance and current expectations and
projections about our future financial results, goals, plans and
objectives and involve inherent risks, assumptions and
uncertainties, including internal or external factors that could
delay, divert or change any of them in the next several years, that
are difficult to predict, may be beyond our control and could cause
our future financial results, goals, plans and objectives to differ
materially from those expressed in, or implied by, the statements.
These risks, assumptions, uncertainties and other factors include,
among others, that future study results will be consistent with the
results to date, that ORENCIA may not receive regulatory approval
for the additional indication described in this release and, if
approved, whether ORENCIA for such additional indication described
in this release will be commercially successful. No forward-looking
statement can be guaranteed. Forward-looking statements in this
press release should be evaluated together with the many risks and
uncertainties that affect Bristol-Myers Squibb's business and
market, particularly those identified in the cautionary statement
and risk factors discussion in Bristol-Myers Squibb's Annual Report
on Form 10-K for the year ended December 31, 2018, as updated by
our subsequent Quarterly Reports on Form 10-Q, Current Reports on
Form 8-K and other filings with the Securities and Exchange
Commission. The forward-looking statements included in this
document are made only as of the date of this document and except
as otherwise required by applicable law, Bristol-Myers Squibb
undertakes no obligation to publicly update or revise any
forward-looking statement, whether as a result of new information,
future events, changed circumstances or otherwise.
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Inquiries:Chrissy
Trank609-252-5609christina.trank@bms.com
Investors:Tim Power609-252-7509timothy.power@bms.com
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