Subcutaneous Formulation of ORENCIA® (abatacept) Approved by European Commission

Paris (ots/PRNewswire) -

Proven biologic is first therapy available in both subcutaneous
and intravenous formulations for adults with moderate to severe
active rheumatoid arthritis

Bristol-Myers Squibb announced today that the European Commission
has granted marketing authorisation for the subcutaneous formulation
of ORENCIA(R) (abatacept), in combination with methotrexate (MTX),
for the treatment of adults with moderate to severe active rheumatoid
arthritis (RA).

To view the Multimedia News Release, please click:

http://www.epresspack.net/mnr/subcutaneous-formulation-of-orencia
-abatacept-approved-by-european-commission

Most of the currently available biologics for the treatment of RA
are anti-TNF (anti-tumour necrosis factor) agents. ORENCIA works
through a different mechanism of action (T-cell co-stimulation
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 ORENCIA
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 ORENCIA were compared and shown to be
similar in terms of efficacy and safety (non-inferiority comparison).

The intravenous formulation of ORENCIA 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.

ORENCIA, 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 proven efficacy and safety profile",
said Ron Cooper, President, Bristol-Myers Squibb, Europe. "We are
pleased to be able to offer physicians and patients an efficacious
and convenient self-administered formulation."

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 ORENCIA
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 ORENCIA 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).

ACR 50 and 70 responses were comparable between ORENCIA SC and IV
as were improvements in all patient-reported outcomes studied - pain,
physical function and global assessment of disease activity for
ORENCIA SC and IV at month 6.

At month 6, 94% of patients receiving SC injections plus MTX and
94% of patients receiving ORENCIA 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 ORENCIA and 18 (2.5%) patients receiving intravenous
ORENCIA.

This study demonstrated similar safety for patients treated with
subcutaneous ORENCIA and intravenous ORENCIA. These results are
consistent with the safety profile of ORENCIA.[2]

AMPLE (Abatacept Versus Adalimumab Comparison in Biologic-Naïve
rheumatoid arthritis (RA) Subjects With Background
Methotrexate)[4],[5]

In addition to and separate from the pivotal trials, the safety
and efficacy of SC ORENCIA has been shown in the AMPLE study, the
first direct comparison of two biologics on a background of MTX.

Presented for the first time at the EULAR 2012 congress, AMPLE is
a 2-year, head-to-head trial of 646 patients comparing the
subcutaneous (SC) formulation of ORENCIA with adalimumab (HUMIRA(R))
- an anti-TNF - in a standard of care setting, namely on a background
of methotrexate (MTX) for biologic naïve patients with moderate to
severe RA.

AMPLE demonstrated that SC ORENCIA plus MTX achieved comparable
rates of efficacy for the American College of Rheumatology criteria
of 20 percent (ACR20) response at 1 year of 64.8% vs. 63.4% HUMIRA
plus MTX, with similar kinetics of response and inhibition of
radiographic progression at one year.

There were significantly fewer injection site reactions observed
with ORENCIA. The overall safety profiles of the two compounds were
similar.

About ORENCIA(R) (abatacept)

ORENCIA 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).[6],[7],[8],[9].

ORENCIA is the first biologic discovered and developed by
Bristol-Myers Squibb and ORENCIA IV was first approved for adult RA
in May 2007 by the European Commission.

ORENCIA, 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 ORENCIA 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 ORENCIA without an intravenous
loading dose.

The most frequently reported adverse reactions (greater than or
equal to 5%) among ORENCIA-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 ORENCIA, see the Product Information.

ORENCIA 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 ORENCIA
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.[10]

The intravenous formulation of ORENCIA, 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.
ORENCIA has not been studied in children under six years old.

For a full description of ORENCIA, 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_000958.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,[11] a
condition which can severely impact patients' quality of life and can
lead to increased mortality and morbidity.[12] The condition is more
common in women, who account for 75% of patients diagnosed with
RA.[13]

With appropriate treatment, patients can achieve better clinical
outcomes, resulting in more active days and improved well-being.[14]

ORENCIA 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.

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. Schiff M, Fleischmann R, Weinblatt M, et al. EULAR 2012
(Abstract 3409)

5. Schiff M, Fleischmann R, Weinblatt M, et al. EULAR 2012 (Oral
presentation)

6. Kremer M, et al. N Engl J Med 2003;349(20):1907-15.

7. Davis P, et al. Abstract submitted to ACR/ARHP Meeting 2008,
San Francisco Oct 24-29th 2008;08-A-2321-ACR.

8. European Medicines Agency (EMEA). ORENCIA Scientific
Discussion. 2007:1-36.

9. Buch MH, et al. Ann Rheum Dis 2009;68(7):1220-7.

10. European Medicines Agency website. Available at: http://www.e
ma.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/00070
1/human_med_000958.jsp&mid=WC0b01ac058001d124 Last Accessed 5
September 2012.

11. National Rheumatoid Arthritis Foundation Available at: http:/
/www.nras.org.uk/about_rheumatoid_arthritis/living_with_rheumatoid_ar
thritis/employment_benefits/european_fit_for_work_report.aspx Last
accessed 5 September 2012.

12. 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.

13. 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.

14. American College of Rheumatology. Available at: http://www.rh
eumatology.org/practice/clinical/patients/diseases_and_conditions/ra.
asp. Last accessed 5 September 2012.

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

ots Originaltext: Bristol-Myers Squibb GmbH & Co.KG aA
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