Orencia (Abatacept) Demonstrates Consistent Safety And Effectiveness Over 7 Years

- Sustained efficacy observed with ORENCIA over time in patients completing trials -

- AIM trial data show long-term inhibition of structural damage progression -

COPENHAGEN--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE: BMY) today announced results of two ORENCIA® (abatacept) studies at the 2009 Annual European Congress of Rheumatology (EULAR) currently being held in Copenhagen, Denmark.

I. Phase IIb 100 trial (7 years)1

The first, a long-term extension (LTE) study, analysed ORENCIA’s safety and efficacy profile over 7 years of treatment in rheumatoid arthritis (RA) patients who have had an inadequate response to methotrexate (MTX).

Study design

During the 1 year randomised, double-blind (DB) placebo controlled period of this Phase IIb study, 339 patients with active RA and an inadequate response to MTX were randomised to receive either ORENCIA plus MTX or placebo plus MTX. On completion of the DB period, 219 patients entered the open-label LTE, receiving a fixed dose of ORENCIA 10 mg/kg (according to weight range) plus MTX every 4 weeks. During the LTE, safety assessments were performed once a month, and efficacy assessments quarterly.

Outcomes

During the LTE, treatment with ORENCIA and MTX in combination was generally well tolerated, with no increase in the frequency of safety events over time. The cumulative incidence of adverse events (AEs) was 366.1 per 100 patient years, serious AEs was 17.4 per 100 patient years and serious infections was 3.18 per 100 patient years. These data are consistent with previous data on ORENCIA in combination with MTX.

After 7 years, over half (52.1%) of ORENCIA patients (n=85) entering the LTE period remained on treatment. Over this 7 year period, discontinuations due to lack of efficacy and AEs were 11.0% and 19.2%, respectively.

While the LTE was principally designed to examine the long-term safety of ORENCIA, efficacy data were also collected (as observed) in those patients who remained in the LTE. At 7 years, of those patients still on ORENCIA (n=85):

69.7% achieved a low disease activity score (LDAS)
51.5% achieved remission (DAS28-CRP defined)
51.4% achieved an ACR 70 score
“The relevance of these long-term data should not be underestimated for a chronic and progressive disease such as rheumatoid arthritis,” commented Professor René Westhovens, University Hospital Leuven, Belgium. “These patients have to live with the disease, and in many cases, undergo treatment, for the rest of their lives. For both patients and clinicians therefore, it is important that a treatment has a proven long-term safety and efficacy profile.

As part of a comprehensive clinical trial programme, ORENCIA’s safety profile has already been studied through more than 10,000 patient years of exposure. These new data further reinforce ORENCIA, in combination with MTX, as a proven treatment option for moderate to severe active RA in adult patients who have had an insufficient response or intolerance to other disease-modifying anti-rheumatic drugs, including at least one tumour necrosis factor (TNF) inhibitor.2

II. AIM trial (5 years)3

The second study, also presented in Copenhagen this week is the AIM (Abatacept in Inadequate responders to Methotrexate) study LTE, which reinforces the long-term safety and efficacy profile of ORENCIA.

Study design

Of the 433 ORENCIA and 219 placebo treated patients who completed the 1 year, randomised DB, placebo controlled AIM trial, 378 ORENCIA and 161 placebo treated patients entered the open-label LTE period, receiving ORENCIA [~10 mg/kg] plus MTX.

Outcomes: efficacy & safety

ORENCIA patient retention rates remained high in the AIM LTE, with 70.4% of patients (n=266/378) remaining on treatment with ORENCIA plus MTX at year 5. Of these, 33.7% achieved clinical remission (DAS28 defined), and ACR 20, 50 and 70 response rates were 83.6%, 61.1% and 39.6%, respectively, at 5 years.

The types and incidence of AEs and serious AEs were similar between the DB and cumulative (combined DB + LTE) phases. During the DB phase, incidence rates of AEs were 303.4 per 100 patient years and serious AEs, 17.7 per 100 patient years. During the cumulative phase, incidence rates of AEs were 242.3 per 100 patient years and serious AEs, 13.9 per 100 patient years. Incidence rates of serious infections were 4.2 per 100 patient years in the DB period and 2.8 per 100 patient years in the cumulative phase.

Outcomes: inhibition of structural damage progression4

X-ray data from the AIM LTE, also presented at EULAR this week, demonstrated that over 5 years, ORENCIA inhibited structural damage progression in the majority of patients on treatment. 45.1% of patients (n=120) assessed at year 5 continued to show no progression in structural damage. 98% of patients who were non-progressors during years 1-4 remained non-progressors at year 5.

To view presentations on these data from leading RA experts, please log on to the following media webcast:

www.ra-webcast.com

Available from 09:00 CEST on Friday 12 June 2009

About ORENCIA

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 RA.5

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

ORENCIA in combination with methotrexate is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have had an insufficient response or intolerance to other disease-modifying anti-rheumatic drugs including at least one tumour necrosis factor (TNF) inhibitor.

A reduction in the progression of joint damage and improvement of physical function have been demonstrated during combination treatment with ORENCIA and methotrexate.

The safety profile of ORENCIA has been studied through more than 10,000 patient-years of exposure and has demonstrated a consistent safety profile to 7 years.2

Medicinal products, including ORENCIA, which affect the immune system, may affect host defences against infections and malignancies. 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). 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%. These rates are similar to that observed in the general RA population.6

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.

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.7,8

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to extend and enhance human life.

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

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

References:

1 Westhovens, R et al. Consistent Safety and Sustained Improvement in Disease Activity and Treatment Response Over 7 Years of Abatacept Treatment in Biologic-Naïve Patients with RA. EULAR 2009, abstract no. FRI0108.

2 Smitten, A et al. Descriptive Analysis of Serious Infections, Hospitalized Infections and Malignancies Over Time in the Abatacept Clinical Development Program: A Safety Update with >10,000 Person-Years of Exposure. EULAR 2008, abstract no. 1065.

3 Kremer JM et al. Abatacept Demonstrates Consistent Safety and Sustained Improvements in Efficacy Through 5 Years of Treatment in Biologic-Naïve Patients with RA. EULAR 2009, abstract no. FRI0263.

4 Genant, HK el al. Abatacept Increases the Proportion of Patients who Remain Free From Structural Damage Progression Through 5 Years in Methotrexate Inadequate Responders with RA.EULAR 2009, abstract no. FRI0253.

5 Kremer, JM et al. Treatment of Rheumatoid Arthritis by Selective Inhibition of T-Cell Activation with Fusion Protein CTLA4Ig. N. Engl. J. Med. 2003;349:1907–1915.

6 Simon, T et al. Ann Rheum Dis 2006;65(Suppl II):489.

7 United Nations. 2008 Revision Population Database.

8 Symons, D et al. The Global Burden of Rheumatoid Arthritis in the Year 2000.

Posted: June 2009

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