ORENCIA® (abatacept) Shows Comparable Efficacy to Humira® (adalimumab) in
Year Two Data from Head-to-Head Study in Patients with Moderate to Severe
AMPLE Study results highlighted during a press conference at the European
League Against Rheumatism (EULAR) Annual congress
*Year 2 data shows similar efficacy between ORENCIA plus methotrexate (MTX)
and Humira plus MTX, consistent with the year 1 result which demonstrated
comparable efficacy based on a non-inferiority endpoint for ACR 20
*Radiographic non-progression at 2 years was achieved by 85 percent of
patients on ORENCIA plus MTX and 84 percent of patients on Humira plus MTX
*The frequency of adverse events was overall similar in both groups; there
were numerically fewer discontinuations due to adverse events, serious
adverse events, serious infections, and fewer local injection site
reactions in patients treated with ORENCIA plus MTX
PRINCETON, N.J. -- June 11, 2013
Bristol-Myers Squibb Company (NYSE: BMY) today announced the results of year
two data from AMPLE (Abatacept Versus Adalimumab Comparison in Biologic-Naïve
rheumatoid arthritis (RA) Subjects With Background Methotrexate), a
first-of-its-kind trial of 646 patients comparing the subcutaneous (SC)
formulation of ORENCIA^® (abatacept) vs. Humira^® (adalimumab), each on a
background of MTX, in biologic naïve patients with moderate to severe RA. The
AMPLE year two data are being presented this week at the European League
Against Rheumatism (EULAR) annual congress and highlighted during a congress
AMPLE met its primary endpoint as measured by non-inferiority of ACR20
(American College of Rheumatology 20 percent improvement) at year one. The
ORENCIA regimen achieved comparable rates of efficacy vs. the Humira regimen
(64.8% vs. 63.4%, respectively). Onset of response was also generally similar
for the two groups.
Year two of the study remained investigator-blinded. At year two, the ORENCIA
regimen achieved the same rate of efficacy (60%) as the Humira regimen based
on ACR20. ACR50, 70, and 90, considered to be more stringent measures of
efficacy, as well as DAS-28-CRP, were assessed over 24 months and were
generally similar for the two arms.
Radiographic progression was also assessed at two years with 85% of patients
on the ORENCIA regimen and 84% of patients on the Humira regimen achieving
“Results from the second year of the AMPLE study confirm what we saw in year
one data,” said Michael Schiff, M.D., M.A.C.R., University of Colorado, and
principal AMPLE study investigator, “namely, that efficacy was comparable for
the two agents in this study.”
At 24 months, overall safety data were similar for both groups, including
frequency of adverse events (92.8% and 91.5%), serious adverse events (13.8%
and 16.5%), and malignancies (2.2% and 2.1%) for the ORENCIA regimen and the
Humira regimen, respectively. Discontinuations due to adverse events were 3.8%
for the ORENCIA regimen and 9.5% for the Humira regimen, while
discontinuations due to serious adverse events were 1.6% for the ORENCIA
regimen and 4.9% for the Humira regimen. Additionally, zero of the 12 patients
who experienced serious infections in the ORENCIA group discontinued, while
nine of the 19 patients who experienced serious infections in the Humira group
discontinued. Autoimmune events, of mild or moderate severity, were reported
in 3.8% of patients in the ORENCIA group and 1.8% of patients in the Humira
group. Injection site reactions were reported in 4.1% of patients taking the
ORENCIA regimen and 10.4% of patients taking the Humira regimen.
“The two year follow-up data from AMPLE provide important information on the
clinical profile of abatacept (ORENCIA) plus MTX as a first biologic treatment
option for patients with severe to moderate RA,” said Dr. Schiff.
About the Study
AMPLE is a phase IIIb randomized, investigator-blinded multinational study of
24 months duration with a 12 month efficacy primary endpoint (non-inferiority
for ACR20). The study included 646 adult biologic-naïve patients with active
moderate to severe RA and inadequate response to MTX; 318 in the ORENCIA plus
MTX group and 328 in the Humira plus MTX group. Patients were stratified by
disease activity and randomized to either 125 mg ORENCIA SC weekly or 40 mg
Humira every other week, both on background MTX. The primary endpoint was to
determine non-inferiority of ORENCIA plus MTX to Humira plus MTX based on
ACR20 response at 12 months. Secondary endpoints included injection site
reactions, radiographic non-progression as assessed using the van der Heijde
modified total Sharp score (mTSS) method, safety and retention. The complete
year one study results were published in the January 2013 volume of
Arthritis& Rheumatism, the official monthlyjournalof the American College
Detailed Study Results
Of 646 patients who were randomized and treated, 79.2% (252 of 318) ORENCIA
plus MTX patients and 74.7% (245 of 328) Humira plus MTX patients completed
the full 24 month study.
Comparable ACR20 response rates at year two were 59.7% for ORENCIA plus MTX
and 60.1% for Humira plus MTX.
Onset of response was also generally comparable between the two groups for
ACR20, 50 and 70 with responses remaining comparable through two years.
Additionally, 30.2% patients in both treatment groups showed a major clinical
response (an ACR70 score maintained for ≥6 months) at two years. A DAS28-CRP
score ≤3.2 was achieved by 65.3% of ORENCIA plus MTX patients and 68.0% of
HUMIRA plus MTX patients, while 50.6% of ORENCIA plus MTX and 53.3% of HUMIRA
plus MTX achieved a score <2.6.
Paired radiographic images were available at baseline and year two for 80.8%
(257/318) and 79.3% (260/328) of patients in the ORENCIA plus MTX and Humira
plus MTX groups respectively. The distribution of change in total score from
baseline to year two showed that inhibition of radiographic damage was similar
in both treatment groups, and included most patients. Inhibition of
radiographic progression was seen in both component scores (Erosion Score: 0.4
± 2.6 and 0.4 ± 5.0; Joint Space Narrowing Score: 0.5 ± 2.2 and 0.7 ± 3.8) in
the ORENCIA plus MTX and Humira plus MTX groups respectively. At year two, the
non-progression rate (change from baseline ≤SDC =2.2) was 84.8% and 83.8% in
the ORENCIA plus MTX and Humira plus MTX groups respectively.
At year two, the cumulative rates of adverse events (AEs) were 92.8% and
91.5%, and serious adverse events were 13.8% and 16.5%, in the ORENCIA plus
MTX and Humira plus MTX groups, respectively. Discontinuations due to AEs
occurred in 3.8% and 9.5% of the ORENCIA plus MTX and Humira plus MTX patients
respectively (estimate of difference: -5.7 [95%CI: -9.5, -1.9]).
Discontinuations due to SAEs occurred in 1.6% and 4.9% in the ORENCIA plus MTX
and Humira plus MTX groups respectively (estimate of difference: -3.3 [95%CI:
-9.5, -1.9]). One death occurred in each treatment group, neither of which was
attributed to the study medications. Overall, 76.1% of the ORENCIA plus MTX
patients and 71.3% of the Humira plus MTX patients had an infection over two
years. During the study period, serious infections occurred in 12 (3.8%) and
19 (5.8%) patients of which five and 10 occurred during year two, for ORENCIA
plus MTX vs. Humira plus MTX, respectively. Discontinuations due to serious
infections were zero of the 12 patients with serious infections for Orencia
plus MTX compared to nine of the 19 patients with serious infections, for
Humira plus MTX. Injection site reactions were reported in 4.1% of patients
taking ORENCIA plus MTX and 10.4% of patients taking Humira plus MTX over two
years. Autoimmune events, of moderate or mild severity, were reported in 12
patients (3.8%) in the ORENCIA plus MTX group and six patients (1.8%) in the
Humira plus MTX group. Malignancies occurred in seven patients (2.2%) in the
ORENCIA plus MTX group and seven patients (2.1%) in the Humira plus MTX group.
About Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a systemic, chronic, autoimmune disease
characterized by inflammation in the lining of joints (or synovium), causing
joint damage with chronic pain, stiffness, swelling and fatigue. RA causes
limited range of motion and decreased joint function. The condition is more
common in women than in men, who account for 75% of patients diagnosed with
ORENCIA SC and IV 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 rheumatoid arthritis. ORENCIA may be used as monotherapy or
concomitantly with disease-modifying antirheumatic drugs (DMARDs) other than
tumor necrosis factor (TNF) antagonists.
ORENCIA IV is indicated for reducing signs and symptoms in pediatric patients
6 years of age and older with moderately to severely active polyarticular
juvenile idiopathic arthritis. ORENCIA IV may be used as monotherapy or
concomitantly with methotrexate (MTX). ORENCIA SC has not been studied in
ORENCIA should not be administered concomitantly with TNF antagonists. ORENCIA
is not recommended for use concomitantly with other biologic rheumatoid
arthritis (RA) therapy, such as anakinra.
ORENCIA is intended for use under the guidance of a physician or healthcare
Important Safety Information
Concomitant Use with TNF antagonists:Concurrent therapy with ORENCIA and a
biologic DMARD is not recommended. In controlled clinical trials, adult
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:Less than 1% of adult patients treated with ORENCIA
experienced hypersensitivity reactions, including some cases of anaphylaxis or
anaphylactoid reactions. Other events potentially associated with drug
hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred
in less than 0.9% of patients treated with ORENCIA^® (abatacept) and generally
occurred within 24 hours of infusion. There was 1 case of a hypersensitivity
reaction with ORENCIA in JIA clinical trials (0.5%; n =190). Appropriate
medical support measures for treating hypersensitivity reactions should be
available for immediate use in the event of a reaction.
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 as it 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 (abatacept) developed adverse events more
frequently than those treated with placebo (97% vs. 88%, respectively).
Respiratory disorders occurred more frequently in patients treated with
ORENCIA compared to those on placebo (43% vs. 24%, respectively), including
COPD exacerbations, cough, rhonchi, and dyspnea. A greater percentage of
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 pyrroloquinolinequinone (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 administration does not contain maltose; therefore, patients do
not need to alter their glucose monitoring.
Pregnant and Nursing Mothers:ORENCIA^®(abatacept) should be used during
pregnancy only if clearly needed. The risk for development of autoimmune
diseases in humans exposedin uteroto abatacept has not been determined.
Nursing mothers should be informed of the risk/benefit of continued
breast-feeding or discontinuation of the drug. A pregnancy registry has been
established to monitor fetal outcomes. Healthcare professionals are encouraged
to register pregnant patients exposed to ORENCIA by calling 1-877-311-8972.
Most Serious Adverse Reactions:Serious infections (3% ORENCIA vs. 1.9%
placebo) and malignancies (1.3% ORENCIA vs. 1.1% placebo). In general, adverse
events in pediatric and adolescent patients were similar in frequency and type
to those seen in adult patients.
Malignancies:The overall frequency of malignancies was similar between adult
patients treated with ORENCIA (abatacept) or placebo. However, more cases of
lung cancer were observed in 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.
For USFull Prescribing Information, visit
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, visitwww.bms.com, or follow
us on Twitter athttp://twitter.com/bmsnews.
ORENCIA^® is a registered trademark of Bristol-Myers Squibb Company.
Bristol-Myers Squibb Forward Looking Statement
This press release contains "forward-looking statements" as that term is
defined in the Private Securities Litigation Reform Act of 1995 regarding
product development. Such forward-looking statements are based on current
expectations and involve inherent risks and uncertainties, including factors
that could delay, divert or change any of them, and could cause actual
outcomes and results to differ materially from current expectations. No
forward-looking statement can be guaranteed. Among other risks, there can be
no guarantee that the clinical trials of these compounds will support
regulatory filings, or that the compounds will receive regulatory approvals
or, if approved, that they will become commercially successful products.
Forward-looking statements in this press release should be evaluated together
with the many uncertainties that affect Bristol-Myers Squibb's business,
particularly those identified in the cautionary factors discussion in
Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December
31, 2012, in our Quarterly Reports on Form 10-Q and our Current Reports on
Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information, future
events or otherwise.
Chris Clark, 609-252-6269
Celine Van Doosselaere, +33-1-5883-6027
John Elicker, 609-252-4611
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