Subcutaneous Formulation of ORENCIA® (abatacept)
Approved by European Commission
First biologic therapy available in both subcutaneous and intravenous formulations for adults
with moderate to severe active rheumatoid arthritis
[Paris, France. 5 October 2012] – Bristol-Myers Squibb announced today that the European
Commission has granted marketing authorisation for the subcutaneous formulation of
ORENCIA® (abatacept), in combination with methotrexate (MTX), for the treatment of adults
with moderate to severe active rheumatoid arthritis (RA).
Most of the currently available biologics for the treatment of RA are anti-TNF (anti-tumour
necrosis factor) agents. Abatacept works through a different mechanism of action (T-cell costimulation modulation) and is the only agent available in both self-injectable, subcutaneous
(SC) and intravenous (IV) formulations. Given that some patients prefer one route of
administration for specific reasons, the availability of both formulations addresses the needs and
preferences of patients and physicians.1
“ORENCIA is a true alternative to anti-TNFs – a first-line biologic therapy for RA patients that
now also offers the convenience of self-administration in a subcutaneous formulation,” said Prof.
Dr. Rieke Alten, Chief Physician, Department of Internal Medicine, Rheumatology, Clinical
Immunology and Osteology Schlosspark Clinic, Berlin. “ORENCIA provides a choice when
deciding how to treat adults with moderate to severe active RA by offering a proven mechanism
of action that is different from anti-TNFs.”
The European approval of the subcutaneous formulation of abatacept is based on the ACQUIRE
study, a pivotal phase III registrational trial, as well as long-term efficacy and safety data from
supporting phase II studies. In ACQUIRE, the single largest phase III registrational trial of
biologics in RA patients, the subcutaneous and intravenous formulations of abatacept were
compared and shown to be similar in terms of efficacy and safety (non-inferiority comparison).
1
The intravenous formulation of abatacept was first approved in the European Union in May 2007
and is a well-established treatment option for adult RA patients who have an inadequate response
to methotrexate alone or who have failed a first biologic DMARD.
Abatacept, in combination with methotrexate (MTX), is indicated for the treatment of moderate to
severe active RA in adult patients who responded inadequately to previous therapy with one or
more disease-modifying anti-rheumatic drugs (DMARDs), including MTX or a tumour necrosis
factor (TNF)-alpha inhibitor.2
“Many physicians use intravenous ORENCIA for RA because it has a unique mechanism of
action and a well-recognised efficacy and safety profile,” said Ron Cooper, President, BristolMyers Squibb. Europe. “We are pleased to be able to offer physicians and patients an efficacious
and convenient self-administered formulation.”
- Ends Notes to editors
Clinical Trials
ACQUIRE (Abatacept Comparison of Sub[QU]cutaneous versus Intravenous in inadequate
Responders to methotrexate) 3
In ACQUIRE, the goal was to demonstrate non-inferiority of the efficacy and comparability of the
safety of subcutaneous abatacept relative to intravenous administration in subjects with moderate
to severe active RA and experiencing inadequate response to MTX.
The trial, which was a randomised, multinational phase III study of 1,457 patients, showed that
abatacept achieved comparable rates of efficacy for the American College of Rheumatology
criteria of 20 percent (ACR20) response at month 6 in both groups of patients receiving SC
injections plus methotrexate (MTX) or IV infusions plus MTX (76.1 % vs 75.7, respectively).
2
ACR 50 and 70 responses were comparable between abatacept SC and IV as were improvements
in all patient-reported outcomes studied – pain, physical function and global assessment of disease
activity for abatacept SC and IV at month 6.
At month 6, 94% of patients receiving SC injections plus MTX and 94% of patients receiving
abatacept IV plus MTX remained in the study. The rate of injection site reactions (mostly mild)
was similar across both patient groups, occurring in 19 (2.6%) patients receiving subcutaneous
abatacept and 18 (2.5%) patients receiving intravenous abatacept.
This study demonstrated similar safety for patients treated with subcutaneous abatacept and
intravenous abatacept. These results are consistent with the safety profile of abatacept.2
About ORENCIA® (abatacept)
Abatacept is a selective co-stimulation modulator of T-cell activation. It is designed to prevent full
T-cell activation and inhibit the release of chemicals leading to joint inflammation and destruction
as observed in rheumatoid arthritis (RA).4,5,6,7.
Abatacept is the first biologic discovered and developed by Bristol-Myers Squibb and abatacept
IV was first approved for adult RA in May 2007 by the European Commission.
Abatacept, in combination with methotrexate (MTX), is indicated for the treatment of moderate to
severe active RA in adult patients who responded inadequately to previous therapy with one or
more disease-modifying anti-rheumatic drugs (DMARDs) including MTX or a tumor necrosis
factor (TNF) inhibitor. A reduction in the progression of joint damage and improvement of
physical function has been demonstrated during combination treatment with abatacept and MTX.
The new self-injectable formulation can be administered weekly through an injection under the
skin following a single IV loading dose. Patients who are unable to receive an infusion may
initiate weekly injections of subcutaneous abatacept without an intravenous loading dose.
Date of preparation: September 2012, 427UK12NP053
3
The most frequently reported adverse reactions (≥ 5%) among abatacept-treated patients are
headache, nausea, and upper respiratory tract infections. In younger patients, side effects are
similar to adults. For the full list of all side effects reported with abatacept, see the Product
Information.
Abatacept should not be prescribed to persons who are hypersensitive to abatacept or any of the
other ingredients. It must not be used in patients with severe and uncontrolled infections, such
as sepsis or opportunistic infections. Patients who receive abatacept are given a special alert
card that explains this restriction and instructs them to contact their doctor immediately if they
develop an infection during a course of treatment.8
The intravenous formulation of abatacept, in combination with MTX, is also indicated for the
treatment of moderate to severe active polyarticular Juvenile Idiopathic Arthritis (pJIA) in
paediatric patients six years of age and older who have had an insufficient response to other
DMARDs, including at least one TNF inhibitor. Abatacept has not been studied in children under
six years old.
For a full description of abatacept, including efficacy and safety profile, please consult the
Summary of Product Characteristics (SmPC):
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000701/human_med_00
0958.jsp&mid=WC0b01ac058001d124
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.
In Europe, more than 2.9 million people are affected by RA,9 a condition which can severely
impact patients’ quality of life and can lead to increased mortality and morbidity.10 The condition
is more common in women, who account for 75% of patients diagnosed with RA.11
Date of preparation: September 2012, 427UK12NP053
4
With appropriate treatment, patients can achieve better clinical outcomes, resulting in more active
days and improved well-being.12
Abatacept is one of the biologic treatment options indicated in adult patients with moderate to
severely active RA for patients who respond inadequately to previous DMARDs. The approval of
the new subcutaneous formulation will offer one more option, giving some patients the
opportunity to treat themselves at home.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company committed to discovering,
developing and delivering innovative medicines that help patients prevail over serious diseases.
ORENCIA is a registered trademark of Bristol-Myers Squibb Company. All other trademarks are
property of their respective owners.
###
Media: Celine Van Doosselaere, celine.vandoosselaere@bms.com, +33.1.58.83.60.27
Investors: John Elicker, john.elicker@bms.com, +1 (609) 252-4611
References
1
Scarpato S, et al. “Patient preferences in the choice of anti-TNF therapies in rheumatoid arthritis. Results from a questionnaire
survey (RIVIERA study)” Rheumatology (2010) 49 (2): 289-294. doi: 10.1093/rheumatology/kep354. First published online:
November 17, 2009
2
Orencia SmPC.
3 Genovese MC et al. Subcutaneous abatacept versus intravenous abatacept: a phase IIIb non-inferiority study in patients with an
inadequate response to methotrexate. Arthritis Rheum 2011;63:2854–64. doi: 10.1002/art.30463
4 Kremer M, et al. N Engl J Med 2003;349(20):1907-15.
5 Davis P, et al. Abstract submitted to ACR/ARHP Meeting 2008, San Francisco Oct 24-29th 2008;08-A-2321-ACR.
6 European Medicines Agency (EMEA). ORENCIA Scientific Discussion. 2007:1-36.
7 Buch MH, et al. Ann Rheum Dis 2009;68(7):1220-7.
8 European Medicines Agency website. Available at:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000701/human_med_000958.jsp&mid=WC0b0
1ac058001d124 Last Accessed 5 September 2012.
9 National Rheumatoid Arthritis Foundation Available at:
http://www.nras.org.uk/about_rheumatoid_arthritis/living_with_rheumatoid_arthritis/employment_benefits/european_fit_for_work
_report.aspx Last accessed 5 September 2012.
10 March L and Lapsley H. “What are the costs to society and the potential benefits from the effective management of early
rheumatoid arthritis?” Best Practice & Research Clinical Rheumatology 2001;15(1):171-185.
11 National Institute of Arthritis and Musculoskeletal and Skin Diseases. National Institutes of Health. U.S.Department of Health
and Human Services. Rheumatoid Arthritis. May 2004.
12 American College of Rheumatology. Available at:
http://www.rheumatology.org/practice/clinical/patients/diseases_and_conditions/ra.asp. Last accessed 5 September 2012.
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