ORENCIA® (abatacept) Shows Comparable Efficacy to Humira® (adalimumab) in Year Two Data from Head-to-Head Study in Patients with Moderate to Severe Rheumatoid Arthritis

PARIS, June 11, 2013 /PRNewswire/ --

AMPLE Study results highlighted during a press conference at the European League Against Rheumatism (EULAR) Annual congress

• Year 2 data shows similar efficacy between ORENCIA plus methotrexate (MTX) and Humira plus MTX, consistent with the year 1 result which demonstrated comparable efficacy based on a non-inferiority endpoint for ACR 20 response
• Radiographic non-progression at 2 years was achieved by 85 percent of patients on ORENCIA plus MTX and 84 percent of patients on Humira plus MTX
• The frequency of adverse events was overall similar in both groups; there were numerically fewer discontinuations due to adverse events, serious adverse events, serious infections, and fewer local injection site reactions in patients treated with ORENCIA plus MTX

Bristol-Myers Squibb Company (NYSE: BMY) today announced the results of year two data from AMPLE (Abatacept Versus Adalimumab Comparison in Biologic-Naïve rheumatoid arthritis (RA) Subjects With Background Methotrexate), a first-of-its-kind trial of 646 patients comparing the subcutaneous (SC) formulation of ORENCIA^® (abatacept) vs. Humira^® (adalimumab), each on a background of MTX, in biologic naïve patients with moderate to severe RA. The AMPLE year two data were presented today at the European League Against Rheumatism (EULAR) Annual congress and highlighted during a congress press conference.

AMPLE met its primary endpoint as measured by non-inferiority of ACR20 (American College of Rheumatology 20 percent improvement) at year one. The ORENCIA regimen achieved comparable rates of efficacy vs. the Humira regimen (64.8% vs. 63.4%, respectively). Onset of response was also generally similar for the two groups.

Year two of the study remained investigator-blinded. At year two, the ORENCIA regimen achieved the same rate of efficacy (60%) as the Humira regimen based on ACR20. ACR50, 70, and 90, considered to be more stringent measures of efficacy, as well as DAS-28-CRP, were assessed over 24 months and were generally similar for the two arms.

Radiographic progression was also assessed at two years with 85% of patients on the ORENCIA regimen and 84% of patients on the Humira regimen achieving radiographic non-progression.

"Results from the second year of the AMPLE study confirm what we saw in year one data," said Michael Schiff, M.D., M.A.C.R., University of Colorado, and principal AMPLE study investigator, "namely, that efficacy was comparable for the two agents in this study."

At 24 months, overall safety data were similar for both groups, including frequency of adverse events (92.8% and 91.5%), serious adverse events (13.8% and 16.5%), and malignancies (2.2% and 2.1%) for the ORENCIA regimen and the Humira regimen, respectively. Discontinuations due to adverse events were 3.8% for the ORENCIA regimen and 9.5% for the Humira regimen, while discontinuations due to serious adverse events were 1.6% for the ORENCIA regimen and 4.9% for the Humira regimen. Additionally, zero of the 12 patients who experienced serious infections in the ORENCIA group discontinued, while nine of the 19 patients who experienced serious infections in the Humira group discontinued. Autoimmune events, of mild or moderate severity, were reported in 3.8% of patients in the ORENCIA group and 1.8% of patients in the Humira group. Injection site reactions were reported in 4.1% of patients taking the ORENCIA regimen and 10.4% of patients taking the Humira regimen.

"The 2 year follow-up data from AMPLE provide important information on the clinical profile of ORENCIA plus MTX as a first biologic treatment option for patients with severe to moderate RA," said Dr. Schiff.

Notes to editors

About the AMPLE study^[i],[ii]

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

Presented at the 2013 European League Against Rheumatism (EULAR) Annual congress, AMPLE is a 2-year, head-to-head trial of 646 patients comparing the subcutaneous (SC) formulation of abatacept with adalimumab  - 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.

The primary endpoint of the study was to determine non-inferiority of abatacept plus MTX to adalimumab plus MTX based on ACR 20 at 12 months. Secondary endpoints at one and two years included inhibition of radiographic progression, safety, injection site reactions and retention.

AMPLE demonstrated that SC 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% HUMIRA plus MTX, with similar kinetics of response and inhibition of radiographic progression at one year. At year two, comparable efficacy was maintained, with 60% of patients on either abatacept or adalimumab achieving an ACR20 response. Both agents achieved similar response rates (ACR20, 50, 70 and 90), disease status scores (DAS 28-CRP, SDAI, CDAI) and levels of radiographic progression inhibition.

The overall safety data were similar for abatacept and adalimumab, including incidence of AEs (92.8% vs 91.5%), SAEs (13.8% vs 16.5%) and malignancies (2.2% vs 2.1%), with some notable exceptions:

• Discontinuations due to AEs were less than half as common with abatacept compared with adalimumab (3.8% vs 9.5%).
• Discontinuations due to SAEs with abatacept were also less than half as common compared with adalimumab (1.6% vs 4.9%).
• Autoimmune events were reported in 3.8% of patients in the abatacept group and 1.8% of patients in the adalimumab group. All of these autoimmune events were mild or moderate in severity and are consistent with those expected in an RA population.

In addition, in terms of tolerability, injection-site reactions occurred less frequently in those treated with abatacept compared with adalimumab (4.1% vs 10.4%, no discontinuation with abatacept) at 12 months.

The types of AEs and SAEs were consistent with those shown in previous abatacept or adalimumab studies.

About abatacept

Abatacept is the first RA biologic agent to be available in both an intravenous (IV) and a self-injectable, subcutaneous (SC) formulation.^[iii],[iv]

Abatacept, in either injectable formulation (IV or SC), is a treatment designed to reduce the signs and symptoms, reduce the progression of joint damage and improve physical function in adults with rheumatoid arthritis (RA). In Europe, it is indicated for use in combination with methotrexate (MTX) to treat moderate to severe active RA in adults who have had an inadequate response to a disease-modifying anti-rheumatic drug (DMARD), including MTX or a tumour necrosis factor (TNF) antagonist (also known as an anti-TNF).

In addition, abatacept IV is approved for use in children six years of age and older with polyarticular juvenile idiopathic arthritis (JIA) who have responded inadequately to other treatments including at least one anti-TNF agent.

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__Product_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.

In Europe, more than 2.9 million people are affected by RA,^[v] a condition which can severely impact patients' quality of life and can lead to increased mortality and morbidity.^[vi] The condition is more common in women, who account for 75% of patients diagnosed with RA.^[vii]

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

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 in 2012 offers 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.

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

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

iii. Orencia IV SPC. Available from: http://www.medicines.org.uk/emc/medicine/19714/SPC/ORENCIA+250+mg+powder+for+concentrate+for+solution+for+infusion/ [http://www.medicines.org.uk/emc/medicine/19714/SPC/ORENCIA+250+mg+powder+for+concentrate+for+solution+for+infusion ] Last accessed: May 2013

iv. Orencia SC SPC. Available from: http://www.medicines.org.uk/emc/medicine/27216/SPC/ORENCIA+125+mg+solution+for+injection+(pre-filled+syringe)/ [http://www.medicines.org.uk/emc/medicine/27216/SPC/ORENCIA+125+mg+solution+for+injection+(pre-filled+syringe) ] Last accessed: May 2013

v. 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.

vi. 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.

vii. 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.

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

SOURCE Bristol-Myers Squibb