-
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)
PRINCETON, N.J.–(BUSINESS WIRE)–$BMY—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
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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.
Contacts
Bristol-Myers Squibb Company
Media Inquiries:
Chrissy
Trank
609–252–5609
christina.trank@bms.com
Investors:
Tim Power
609-252-7509
timothy.power@bms.com