European Commission Approves Bristol-Myers Squibb’s ORENCIA® (abatacept) for the Treatment of Highly Active and Progressive Disease in Adult Patients with Rheumatoid Arthritis Not Previously Treated with Methotrexate
ORENCIA is the first biologic therapy with an EU indication
specifically applicable to the treatment of MTX-naive RA patients with
highly active and progressive disease
This approval marks the first time that MRI assessment of
structural and inflammatory measures of disease severity are cited in
SmPC to support an RA indication
PRINCETON, N.J.–(BUSINESS WIRE)–$BMY #Arthritis—Bristol-Myers
Squibb Company (NYSE: BMY) today announced that the European
Commission has approved ORENCIA® (abatacept)
intravenous (IV) infusion and subcutaneous (SC) injection, in
combination with methotrexate (MTX), for the treatment of highly active
and progressive disease in adult patients with rheumatoid arthritis (RA)
not previously treated with MTX. With this approval, ORENCIA is
the first biologic therapy with an indication in the European Union (EU)
specifically applicable to the treatment of MTX-naive RA patients with
highly active and progressive disease. Studies of ORENCIA
involving adult patients with high disease activity (mean DAS28-CRP of
5.4) accompanied by poor prognostic factors for rapidly progressive
disease (positive for anti-CCP antibodies (also known as ACPA), and/or
RF+, presence of baseline joint erosions) provided the clinical trial
evidence supporting the recommendation. This approval allows for the
expanded marketing of ORENCIA in all 28 Member States of the EU.
“Across the globe we remain committed to advancing care for those living
with RA. The European Commission’s approval of ORENCIA in the EU
for MTX-naive RA patients who have highly active and progressive disease
is a testament to Bristol-Myers Squibb’s commitment to advancing the
science of earlier identification of patients with progressive RA prior
to their suffering debilitating joint damage,” said Brian J. Gavin, Vice
President, ORENCIA Development Lead at Bristol-Myers Squibb.
The approval was based on data from two Phase 3 studies: In a 12 month,
multinational, double-blind, randomized, Phase 3B study of MTX-naive
patients with early, rapidly progressing RA, ORENCIA IV + MTX
demonstrated significant efficacy vs MTX alone for those with moderate
to severe RA.1 The study, AGREE (Abatacept study to Gauge
Remission and joint damage progression in MTX-naive patients with Early
Erosive RA), met its co-primary endpoints as defined by the
proportion of patients achieving DAS28-CRP < 2.6 at 1 year (41% vs 23%,
P<0.001) and inhibition of radiographic progression at 1 year (mean
change in total Sharp score: 0.6 vs 1.1, P=0.04).1 Headache,
upper respiratory tract infection, nasopharyngitis, and nausea were the
most commonly reported adverse events occurring at a rate of ≥ 10% in
patients taking ORENCIA in the adult RA clinical studies.1
The second Phase 3 data is from the AVERT (Assessing Very Early
Rheumatoid Arthritis Treatment) study, which
compared ORENCIA 125 mg subcutaneous + MTX combination therapy, ORENCIA
125 mg subcutaneous monotherapy, and MTX monotherapy in induction of
DAS28-defined remission following 12 months of treatment in 351 adult
patients with moderate to severe active, early RA (mean DAS28-CRP of
5.4; mean symptom duration less than 6.7 months) who had not been
treated with MTX or other DMARDs earlier (MTX-naive).2
Patients also had poor prognostic factors for rapidly progressive
disease (positive for anti-CCP antibodies, and/or RF+, presence of
baseline joint erosions).2 The co-primary endpoints compared
the proportion of patients with DAS28-defined remission (DAS28 CRP <2.6)
at month 12 and both months 12 and 18 for ORENCIA + MTX versus
MTX alone.2 At 12 months, significantly more patients on ORENCIA
combination therapy achieved DAS28-defined remission than MTX alone
(60.9%, ORENCIA + MTX; 45.2%, MTX alone).2 Similar
results at 12 months were seen with other measures of efficacy including
Boolean remission (37.0%, ORENCIA + MTX; 22.4%, MTX alone), CDAI
remission (42%, ORENCIA + MTX; 27.6% MTX alone), and SDAI
remission (42%, ORENCIA + MTX; 25% MTX alone).2 The
European Commission’s approval is based on clinical response to ORENCIA
as well as X-Ray and MRI assessments of structural and inflammatory
measures of disease severity.
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 in the
joints.3,4 RA causes decreased range of motion and function
in the joints.3,4 The condition is three times more common in
women than in men.3
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 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 for ORENCIA®
(abatacept)
Concomitant Use with TNF Antagonists: Concurrent therapy with
ORENCIA and a TNF antagonist 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. 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 (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 exacerbation, 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 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 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. Other events
reported in ≥5% of JIA patients were diarrhea, cough, pyrexia, and
abdominal pain. In general, the adverse events in pediatric patients
were similar in frequency and type to those seen in adult patients.
Note concerning SC ORENCIA: The safety and efficacy of SC ORENCIA
have 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 learn 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” 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, 2015 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.
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References |
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| 1. |
Westhovens R, Robles M, Ximenes AC, et al. Clinical Efficacy and Safety of Abatacept in Methotrexate-Naïve Patients with Early Rheumatoid Arthritis and Poor Prognostic Factors. Ann Rheum Dis. 2009;68(12):1870-1877. |
|
| 2. |
Emery P, Huizinga TW, et al. Evaluating Drug-free Remission With Abatacept in Early Rheumatoid Arthritis. Ann Rheum Dis. 2015;74(1):19-26. |
|
| 3. | Rheumatoid Arthritis. American College of Rheumatology. August 2012. | |
| 4. |
Centers for Disease Control and Prevention. Rheumatoid Arthritis. |
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Contacts
Bristol-Myers Squibb Company
Media:
Robert Perry,
407-492-4616
rob.perry@bms.com
or
Investors:
Bill
Szablewski, 609-252-5894
william.szablewski@bms.com
