Bristol-Myers
Squibb Company (NYSE:BMY) today announced results of several new
sub-analyses of the Phase IIIb AVERT (Assessing
Very Early
Rheumatoid arthritis Treatment)
trial that investigated the use of Orencia plus methotrexate
(MTX) in biologic and MTX-naïve citrullinated protein (CCP)-positive
early moderate to severe rheumatoid arthritis (RA) patients. These data
were presented this week at the American College of Rheumatology (ACR)
2014 annual meeting.
Orencia is currently indicated in adults for moderate to severe
RA. Orencia should not be administered with tumor necrosis factor
antagonists and should not be used with other biologic RA drugs.
One of the analyses looked at anti-CCP antibodies, which are a marker of
RA and may contribute to disease progression. The analysis assessed the
development of anti-CCP antibodies in patients with early rapidly
progressing RA by measuring isotypes (related antibody classes) and the
number of epitopes (a specific area of an antigen to which an antibody
binds) recognized after treatment with Orencia plus MTX, Orencia
alone, or MTX alone. Results demonstrated Orencia plus MTX
numerically reduced the concentrations of all CCP isotypes and the
average number of epitopes recognized over one year of treatment more
than Orencia alone or MTX alone.
“Important results were seen in CCP-positive patients,” said T.W.J.
Huizinga, MD, PhD, Leiden University Medical Center, Leiden Netherlands.
“The results of our analysis demonstrate that patients who start
treatment with a combination of Orencia plus methotrexate in
early rheumatoid arthritis may potentially slow disease progression.”
Over 12 months of treatment, 6.7 percent, 12.1 percent, and 7.8 percent
of patients on Orencia plus MTX, Orencia alone, and MTX
alone, respectively, experienced a serious adverse event and 1.7
percent, 4.3 percent and 2.6 percent led to discontinuation. Serious
infections were observed in 0.8 percent of patients in the combination
arm and 3.4 percent in the Orencia monotherapy arm. None of the
patients in the MTX alone arm experienced a serious infection.
Malignancies were reported in 0.8 percent, 1.7 percent, and 0 percent of
patients in the Orencia + MTX, Orencia, and MTX arms,
respectively.
Additional AVERT Sub-Analyses Findings
Additionally at ACR, investigators presented 12-month efficacy data from
AVERT, including new results assessing the effect of Orencia on
more clinically stringent remission criteria than DAS-defined (DAS28 CRP
<2.6) remission, as well as new MRI data.
Significantly more patients on Orencia plus MTX achieved the
stringent clinical endpoint of Boolean-defined remission at 12 months
(37 percent Orencia plus MTX; 26.7 percent Orencia alone;
22.4 percent MTX alone; P<0.05). Higher remission rates as compared to
MTX or Orencia alone were consistent across other clinically
stringent measures, including CDAI remission (42 percent Orencia
plus MTX; 31 percent Orencia alone; 27.6 percent MTX alone;
P<0.05) and SDAI remission (42 percent Orencia plus MTX; 29.3
percent Orencia alone; 25 percent MTX alone; P<0.05). A small but
significantly higher number of patients treated with Orencia plus
MTX were able to maintain drug-free remission up to month 18 and six
months after drug withdrawal, according to the remission threshold of
DAS28-CRP <2.4 (13 percent Orencia plus MTX; vs. 3.5 percent
MTX alone; P=0.002).
Sustained improvements on MRI endpoints were also observed at six months
after stopping combination therapy with Orencia plus MTX vs. MTX
alone, including improved measurements of both joint inflammation and
joint erosion. At 18 months of this post-hoc analysis, the adjusted mean
change from baseline in total synovitis score was -1.34 for Orencia
plus MTX vs. -0.49 for MTX alone; -2.03 for Orencia plus MTX vs.
0.34 for MTX alone in total osteitis score; and 0.13 for Orencia
plus MTX vs. 2.00 for MTX alone in total erosion score (p<0.05 for all
three measures).
“The new AVERT findings presented at ACR reinforce Bristol-Myers
Squibb’s commitment to understanding the disease pathology of RA and the
results associated with earlier treatment with a combination of Orencia
plus methotrexate,” said Douglas Manion, M.D., head of Specialty
Development, Bristol-Myers Squibb. “Collectively, the efficacy, safety
and real-world data presented at ACR will provide clinicians with
valuable insights into treatment response and outcomes in patients with
early rheumatoid arthritis.”
Patient-Reported Outcomes
Orencia plus MTX improved patient-reported outcomes for fatigue,
pain, physical functioning and participation in daily activities
compared to MTX. At 12 months, the Orencia plus MTX treatment arm
reported a significant improvement in fatigue (-34.9) vs. MTX alone
(-26.7; P<0.05); and in health-related quality of life score, 13.9 for Orencia
plus MTX vs. 10.9 for MTX alone; (P<0.05). Recent EULAR recommendations
reinforce the need to assess a treatment’s impact on the patient’s daily
activities and overall quality of life.
About the AVERT Trial
The AVERT trial includes 351 adult patients with symptoms of moderate to
severe RA for less than two years, positive for anti-CCP antibodies,
DAS28 CRP >3.2 and naïve to treatment with methotrexate and biologic
therapies for RA. The patients were randomly assigned to 12 months of
weekly treatment in one of three groups: Orencia 125 mg
subcutaneous plus MTX; Orencia 125 mg subcutaneous alone; or MTX
alone.
Indications/Usage and Important Safety Information for ORENCIA® (abatacept)
Indications/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 is also indicated
for reducing signs and symptoms in pediatric patients aged 6 years and
older with moderately to severely active polyarticular JIA. ORENCIA may
be used as monotherapy or concomitantly with methotrexate (MTX).
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
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: Anaphylaxis or anaphylactoid reactions can
occur during or after an infusion and can be life-threatening. In
controlled, double-blind and open-label clinical trials, anaphylaxis and
anaphylactoid reactions were reported in <0.1% of adult patients dosed
with intravenous ORENCIA. Other reactions potentially associated with
drug hypersensitivity, such as hypotension, urticaria, and dyspnea, that
occurred within 24 hours of ORENCIA infusion, were uncommon (<1% each).
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 (abatacept) 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 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 (SC)
administration does not contain maltose; therefore, patients do not need
to alter their glucose monitoring.
Pregnant and Nursing Mothers: ORENCIA should be used during
pregnancy only if clearly needed. The risk for development of autoimmune
diseases in humans exposed in utero to 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 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.
Note concerning SC ORENCIA: The safety and efficacy of SC ORENCIA
has not been studied in patients under 18 years of age.
Please
see Full Prescribing Information.
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, and swelling. RA
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 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). The
safety and efficacy of Orencia SC has not been studied in
patients under 18 years of age.
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 practitioner.
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 http://www.bms.com,
or follow us on Twitter at http://twitter.com/bmsnews
Orencia is a registered trademark of Bristol-Myers Squibb Company.
About Bristol-Myers Squibb Immunoscience
The immune system is the body’s natural defense against disease. These
processes come into play in almost every human disease. That is why
Bristol-Myers Squibb is focused on exploring ways to harness the body’s
own immune system to treat immune-related diseases with high unmet
medical needs, including RA – a chronic, systemic, inflammatory
autoimmune disorder that affects the joints.
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 the research, development and commercialization of
pharmaceutical products. 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.
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, 2013 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.
Copyright Business Wire 2014