European Commission Approves Bristol-Myers Squibb Company's ORENCIA in Combination with Methotrexate for Earlier Use as First-Line Biologic after DMARD Inadequate Response for the Treatment of Rheumatoid Arthritis

Published: Jul 07, 2010

PARIS--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE: BMY - News) has today announced that on 1 July 2010 the European Commission approved a new indication for ORENCIA® (abatacept), in combination with methotrexate (MTX), for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to previous therapy with one or more disease-modifying anti-rheumatic drugs (DMARDs) including MTX or a TNF-alpha inhibitor.1

“This is a very welcome decision from the European Commission and one which will potentially have a positive impact on treatment outcomes for RA patients who have already experienced inadequate response to a first DMARD,” said Dr. Manuela Le Bars, European Medical Lead for Immunoscience, Bristol-Myers Squibb. “There is a growing body of evidence to show that earlier use of ORENCIA may have significant benefits for patients – for both short-term and long-term efficacy. This new indication means patients have the potential to benefit sooner from incremental improvements in function and quality of life provided by ORENCIA.”

ORENCIA offers potential significant short-term and long-term efficacy

The approval of ORENCIA as a first line biologic after DMARD inadequate response was supported by data from a two-year open-label study from a trial in methotrexate (MTX)-naïve RA patients (AGREE), as well as by long-term open-label data from the core RA clinical trial programme in MTX inadequate responders (IR) (AIM, ATTEST, and a Phase IIb study) and in anti-TNF-IRs (ATTAIN and ARRIVE). These data indicate that ORENCIA may provide improved outcomes in short-term efficacy2,3,4,5 as well as durable and sustained long-term efficacy (up to seven years as demonstrated in the Phase IIb study) when used with MTX earlier in the RA treatment paradigm.6 In addition, a sustained reduction in the rate of progression of structural damage up to five years was demonstrated in the AIM trial.7

* In the AGREE trial in MTX-naïve patients, 53% of patients with RA who had not previously received treatment with a DMARD and were subsequently treated with ORENCIA plus MTX (n=256) achieved ACR50* at six months, compared to 38% of patients who were treated with placebo plus MTX (n=253) (p<0.001);8

* In the AIM trial in MTX-IR, 40% of patients with RA who had an inadequate response to MTX alone and were subsequently treated with ORENCIA plus MTX (n=424) achieved ACR50 at six months, compared to 17% of patients who were treated with placebo plus MTX (n=214) (p<0.001);9

* In the ATTAIN trial in TNF-IR, 20% of patients with RA who had an inadequate response to TNF inhibitors and were subsequently treated with ORENCIA plus DMARDs (n=256) achieved ACR50 at six months compared to 4% of patients who were treated with placebo plus DMARDs (n=133) (p<0.001);10

The ATTEST trial

In the ATTEST trial, which was a randomized double-blind study to assess the efficacy and safety of ORENCIA or infliximab versus placebo in MTX-IR, it was demonstrated that the efficacy of ORENCIA and of infliximab vs. placebo was similar at six months.4 Further improvement was observed with ORENCIA at 12 months4. At six months, the incidences of infections were 48.1% (75), 52.1% (86) and 51.8% (57) and the incidences of infections were 1.3% (2), 4.2% (7) and 2.7% (3) for the ORENCIA, infliximab and placebo groups, respectively.4 At 12 months, the incidences of infections were 59.6% (93), 68.5 (113) and the incidences of infections were 1.9% (3) and 8.5% (14) for the ORENCIA and infliximab groups, respectively.4 In those patients who initially received infliximab and then switched to ORENCIA, the reductions in the mean Disease Activity Score (DAS28)† from baseline were 3.29 at day 729 and 2.48 at day 365.1

“Control of the disease in all its aspects is the goal of treatment in RA,” said Prof. Dr. René Westhovens, of the University of Leuven in Belgium. “As with other DMARDs, ORENCIA has the potential to help patients reach a state of remission. The expanded indication of ORENCIA into an earlier line of RA treatment is part of the wider evolution of RA management that will increasingly allow us to slow the progression of the disease.”

*ACR is an American College of Rheumatology measure for treatment efficacy; ACR50 indicates a 50% improvement in tender or swollen joint counts as well as five other parameters used for disease assessment.

†The Disease Activity Score (DAS) is a combined index that was developed to measure disease activity in patients with Rheumatoid Arthritis (RA). DAS28 refers to the evaluation of disease activity by analysis of 28 joints for swelling or tenderness.

ORENCIA Safety Profile

The safety profile of ORENCIA has been studied in over 11,658 patient-years and it has remained stable up to seven years.11,12,13

In the double-blind and open-label clinical trials in 4,149 patients treated with ORENCIA during these 11,658 patient-years, the incidence rate of serious infections was 2.87 per 100 patient-years and the annualized incidence rate remained stable; the incidence rate of malignancies was 1.43 per 100 patient-years and the annualized incidence rate also remained stable.1 The incidence rate was consistent with that expected in an age- and gender-matched RA population. The incidence rate of autoimmune disorders also remained stable over time, with the most common autoimmune disorder being mild to moderate psoriasis.1

Medicinal products which affect the immune system, including ORENCIA, may affect host defences against infections and malignancies, and affect vaccination responses.

Serious infections, at least possibly related to treatment, were reported in 1.8% of patients with ORENCIA and in 1.0% of patients not treated by ORENCIA (receiving placebo).1 Some of these infections have been fatal. There is a need to evaluate and monitor patients regarding the risk of infection prior to and during treatment. In the placebo-controlled clinical trials, the frequency of malignancies with ORENCIA was 1.4% and with placebo 1.1%.1

ORENCIA, like other biologics, is contraindicated in patients with severe and uncontrolled infections such as sepsis and opportunistic infections and in patients with hypersensitivity to the active substance or to any of the excipients. Allergic reactions have been reported uncommonly with ORENCIA in clinical trials, where patients were not required to be pretreated to prevent allergic reactions. In the case of any serious allergic/anaphylactic reaction, ORENCIA should be discontinued.14,15

About rheumatoid arthritis

RA is a systemic, chronic, autoimmune disease characterised by inflammation in the lining of joints (or synovium), causing joint damage with chronic pain, stiffness and swelling. RA causes limited range of motion and decreased function as a result of affected joints losing their shape and alignment. RA may affect up to 7 million people in Europe.16,17


ORENCIA is a selective co-stimulation modulator of T-cell activation. ORENCIA is designed to prevent full T-cell activation and inhibit the release of chemicals leading to joint inflammation and destruction as observed in RA18,19,20,21 and pJIA.22

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

ORENCIA in combination with 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 DMARDs including MTX or a TNF-alpha inhibitor. A reduction in the progression of joint damage and improvement of physical function have been demonstrated during combination treatment with ORENCIA and MTX.

ORENCIA, in combination with MTX, is also indicated for the treatment of moderate to severe active polyarticular Juvenile Idiopathic Arthritis 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.

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.

ORENCIA® (abatacept) is a trademark of Bristol-Myers Squibb Company.

For information regarding ORENCIA, please consult the Summary of Product Characteristics.

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