Bristol-Myers Squibb GmbH & Co.KG aA

ORENCIA® ? (abatacept) Demonstrates Comparable Efficacy to Humira® (adalimumab) in Patients with Moderate to Severe Rheumatoid Arthritis in First Head-to-Head Study of These Agents

Paris (ots/PRNewswire) - ?

        - ORENCIA demonstrated comparable efficacy to HUMIRA based on a
          non-inferiority endpoint for ACR20 response at 1 year
        - Kinetics of response for ACR20, 50 and 70, and inhibition of radiographic
          progression were generally comparable over 12 months
        - AMPLE is the first head-to-head study in adults with rheumatoid arthritis
          comparing two biologic drugs each on a background of methotrexate 

Bristol-Myers Squibb Company [http://www.bms.com] today announced the results of AMPLE (Abatacept Versus Adalimumab Comparison in Biologic-Naïve rheumatoid arthritis (RA) Subjects With Background Methotrexate), a head-to-head clinical trial of 646 patients comparing the subcutaneous (SC) formulation of ORENCIA(R) (abatacept)vs. HUMIRA(R) (adalimumab), each on a background of methotrexate (MTX), in biologic naïve patients with moderate to severe RA. AMPLE met its primary endpoint (as measured by non-inferiority) and demonstrated that abatacept 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% adalimumab plus MTX.

ACR50, 70 and major clinical response (ACR70 for 6 consecutive months), considered to be more stringent measures of efficacy, as well as DAS-28-CRP, were also assessed at 1 year and found to be generally comparable for the two arms. Kinetics of response and inhibition of radiographic progression were generally comparable for the two groups over a 12-month period. Injection-site reactions (a key secondary endpoint) were statistically significantly fewer in the abatacept plus MTX group. Discontinuations due to adverse events were 3.5% for abatacept plus MTX compared to 6.1% for adalimumab plus MTX while discontinuations due to serious adverse events were 1.3% for abatacept plus MTX compared to 3% for adalimumab plus MTX. Autoimmune events (mild to moderate in severity) reported in the abatacept SC plus MTX group was 3.1% and 1.2% in the adalimumab plus MTX group. Other safety outcomes were similar at 12 months. The results of AMPLE were presented today at the European League Against Rheumatism (EULAR) Annual European Congress of Rheumatology.

"Results from AMPLE provide important information comparing the efficacy of abatacept SC to adalimumab, including kinetics of response," said Michael Schiff, M.D., M.A.C.R., University of Colorado, and principal AMPLE study investigator. "The results demonstrate comparability between two agents for the primary endpoint of ACR20 and provides relevant data on ACR50 and 70."

"AMPLE is the first head-to-head study between two biologics which incorporates radiographic progression endpoints and provides important data on erosions and joint space narrowing in patients using abatacept SC and adalimumab, both on a background of methotrexate," said Désirée van der Heijde, M.D. Ph.D., Professor of Rheumatology, Leiden University Medical Center.

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 abatacept SCplus MTX group and 328 in the adalimumab plus MTX group. Patients were stratified by disease activity and randomized to either 125 mg abatacept SC weekly (without an IV load) or 40 mg adalimumab every other week, both on background MTX. The primary endpoint was to determine non-inferiority of abatacept SC plus MTX to adalimumab plus MTX by a difference in 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.

Detailed Study Results

Of 646 patients who were randomized and treated, 86.2% (274 of 318) abatacept SC plus MTX patients and 82% (269 of 328) adalimumab plus MTX patients completed 12 months.

Comparable ACR20 response rates at year 1 were 64.8% (95% confidence interval [CI]: 59.5, 70.0) for abatacept SC plus MTX and 63.4% (95% CI: 58.2, 68.6) for adalimumab plus MTX. The estimated difference between groups (95% CI) was 1.8 (-5.6, 9.2) supporting non-inferiority of abatacept SC plus MTX to adalimumab plus MTX.

Kinetics of response was generally comparable between the two groups for ACR20, 50 and 70 through the end of year 1. At 4 weeks, the ACR20 response rates were 42.5% abatacept SC plus MTX vs. 47.6% for adalimumab plus MTX, which remained comparable to the end of year 1 (64.8% abatacept SC plus MTX, 63.4% adalimumab plus MTX). Patients achieved generally comparable ACR50 and ACR70 responses between the abatacept SC plus MTX at year one (ACR50 and 70 were 46.2% and 29.2%, respectively) and adalimumab plus MTX groups (ACR50 and 70 were 46% and 26.2%, respectively).

Abatacept SC plus MTX and adalimumab plus MTX treatment groups showed generally comparable inhibition of radiographic damage; at 12 months, mean change in radiographic non-progression rates as assessed using the mTSS method (0.58 and 0.38, respectively), erosion score (0.29 and -0.01, respectively) and joint narrowing (0.28 and 0.39, respectively) were observed.

Injection-site reactions occurred in significantly fewer patients in the abatacept SCplus MTX group than the adalimumab plus MTX group (3.8% vs. 9.1%, 95% CI: [-9.13, -1.62]; p=0.006). Other safety outcomes were similar between abatacept SC plus MTX and adalimumab plus MTX treatment groups including rates of adverse events (34.9% and 39.9%), serious adverse events (10.1% and 9.1%), overall infections (63.2% and 61.3%), serious infections (2.2% and 2.7%) and malignancies (1.6% and 1.2%), respectively. Discontinuations due to adverse events were 3.5% in the abatacept plus MTX group and 6.1% in the adalimumab plus MTX group and discontinuations due to serious adverse events were 1.3% in the abatacept plus MTX group and 3% in the adalimumab plus MTX group. No serious infections in the abatacept SC plus MTX group led to discontinuation; 5 of the 9 in the adalimumab plus MTX group led to discontinuation. Autoimmune events (mild to moderate in severity) reported in the abatacept SC plus MTX group was 3.1% and 1.2% in the adalimumab plus MTX group.

About ORENCIA(R) (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)[i,ii,iii,iv] and polyarticular Juvenile Idiopathic Arthritis (pJIA).[v]

Abatacept is the first biologic discovered and developed in Bristol-Myers Squibb research centres and abatacept intravenous (IV) was first approved for adult RA in May 2007 by the European Commission. Abatacept SC is not currently licensed in the European Union.

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 antirheumatic drugs (DMARDs) including MTX or a tumor necrosis factor (TNF) antagonist. A reduction in the progression of joint damage and improvement of physical function has been demonstrated during combination treatment with abatacept and MTX.

Abatacept, in combination with MTX, is also indicated for the treatment of moderate to severe active 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.

The most frequently reported adverse reactions (greater than or equal to 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.[vi]

For a full description of abatacept, including efficacy and safety profile, please consult the Summary of Product Characteristics (SmPC):

http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Produ ct_Information/human/000701/WC500048935.pdf

.

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. RA affects about one percent of the world's population[vii], including over 2.9 million[viii] people in the EU. The condition is more common in women than in men, who account for 75% of patients diagnosed with RA.[ix]

Abatacept is one treatment option indicated in adult patients with moderately to severely active RA. In the US, Abatacept may be used as a monotherapy or concomitantly with DMARDs other than TNF antagonists. In the EU, Abatacept may be used only in combination with methotrexate. Abatacept is not recommended for use concomitantly with other biologic RA therapy, such as anakinra.

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

          i) Kremer M, et al. N Engl J Med 2003;349(20):1907-15.
          ii) Davis P, et al. Abstract submitted to ACR/ARHP Meeting 2008, San Francisco
          Oct 24-29th 2008;08-A-2321-ACR.
          iii) European Medicines Agency (EMEA). ORENCIA Scientific Discussion. 2007:1-36.
          iv) Buch MH, et al. Ann Rheum Dis 2009;68(7):1220-7.
          v) Ruperto N, et al. Lancet 2008;372(9636):383-91.
          vi)
       http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000701/human_med_000958.jsp&mid=WC0b01ac058001d124
          EMA website. consulted 10 May 2012.
          vii) World Health Organization. "Chronic rheumatic conditions." Available at
       http://www.who.int/chp/topics/rheumatic/en Accessed on 25 May 2012
          viii) National Rheumatoid Arthritis Society (NRAS) Fit for work report.
          Available at:
       http://www.nras.org.uk/about_rheumatoid_arthritis/living_with_rheumatoid_arthritis/employment_benefits/european_fit_for_work_report.aspx
          . Accessed on 25 May 2012
          ix) 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. 

Contact:

European Media: Celine Van Doosselaere,
celine.vandoosselaere@bms.com, +33-1-58-83-60-27; Non-European Media,
including USA: Ken Dominski, ken.dominski@bms.com, +1-609-252-5251;
Investors: John Elicker, +1-609-252-4611, john.elicker@bms.com



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