Five-Year Data Demonstrate Long-Term Efficacy and Safety with ORENCIA(R) (abatacept) in Adults with Rheumatoid Arthritis Who had an Inadequate Response to Methotrexate

- Data Presented at American College of Rheumatology Annual Meeting -

Bristol-Myers Squibb Company
(NYSE: BMY) today announced that cumulative five-year data from an
open-label long-term extension of a Phase IIb trial demonstrate the
long-term efficacy and safety of ORENCIA(R) (abatacept) in adult rheumatoid
arthritis (RA) patients who had an inadequate response to methotrexate
(MTX). The data show that, in these patients, ORENCIA provided sustained
improvements in ACR responses, physical function and health-related quality
of life. These data, combined with the retention rates observed in this
study, demonstrate that ORENCIA provides durable long-term clinical
benefits in patients with active RA who had an inadequate response to MTX.
Results of this study were presented at the 2007 American College of
Rheumatology (ACR) Annual Scientific Meeting.
    “Studying the long-term efficacy of a treatment is important because RA
is a chronic disease,” said Joel Kremer, M.D., Chief of Rheumatology,
Albany Medical College. “These data are important because they show that
ORENCIA is efficacious and has an acceptable safety profile over an
extended period of time in patients with an inadequate response to
methotrexate.”
    Details of the Study
    Patients in the initial one-year, double-blind, placebo-controlled
randomized trial received MTX and either ORENCIA (10 mg/kg or 2 mg/kg) or
placebo administered as a 30-minute intravenous infusion on Days 1, 15 and
30, and every four weeks thereafter, in addition to MTX. The primary
endpoint of the double-blind portion of the study was ACR 20 at 6 months
(60 percent for ORENCIA(R) (abatacept) vs. 35.5 percent for placebo). All
patients completing the double-blind period were eligible to continue in
the open-label long-term extension, in which all participants received a
fixed dose of ORENCIA approximating 10 mg/kg every four weeks, in addition
to MTX. Efficacy, health- related quality of life and safety were assessed.
    Of the 235 patients completing the double-blind period, 219 entered the
long-term extension (ORENCIA 10 mg/kg=84; ORENCIA 2 mg/kg=68; placebo=67),
and 130 (59.4 percent) continued in the trial for five years. Baseline RA
characteristics for long-term extension patients were similar between
groups at initial randomization (mean disease duration: 8.2 – 9.9 years).
    Data included in this as-observed analysis were from the original group
receiving a dose approximating 10 mg/kg of ORENCIA in the one-year double
blind phase (n=115) through five years’ total treatment (n=56). At Year 1,
improvements in ACR 20, 50 and 70 responses* observed in this group were 77
percent, 53 percent and 29 percent, respectively. At Year 5, improvements
in ACR 20, 50 and 70 responses were sustained (83 percent, 65 percent and
40 percent, respectively). More than one-third of these patients achieved
an ACR 70 response at Year 5.
    Physical function and health-related quality of life were assessed
using the modified Health Assessment Questionnaire Disability Index
(mHAQ-DI) and Short-Form 36 (SF-36), respectively. Clinically meaningful
improvement in physical function was observed in 54.8 percent of patients
at Year 1 and 52.8 percent of patients at Year 5 (n=53). Improvements in
health-related quality of life were also maintained at Year 5. The mean
improvement from baseline in the physical component summary was 9.7 at Year
1 (mean score 40.6) and was stable at 9.7 at Year 5 (mean score 41.7). The
mean improvement in the mental component was 6.1 at Year 1 (mean score
52.3) and 5.4 at Year 5 (mean score 50.8). Improvements in all individual
component scores of the SF-36 were also observed at Year 1 and maintained
at Year 5.
    The safety analysis represents five years of cumulative data. This
includes all patients who received at least one dose of ORENCIA during the
one-year double-blind period and all patients who entered the open-label
period who received at least one dose of ORENCIA plus all patients
randomized to receive placebo (n=287). The incidence rates observed during
the five-year cumulative period for serious adverse events (SAEs),
infections, serious infections, malignancies and autoimmune events were
consistent with both the double-blind period and the integrated safety
summary, which is comprised of seven core RA studies representing
approximately 8,400 patient years of exposure. The incidence rates for SAEs
in the double-blind period, five-year cumulative period and the integrated
safety summary were 20/100 pt-years, 18.9/100 pt-yrs and 15.4/100 pt-yrs,
respectively. The incidence rates for infections in the double-blind
period, five-year cumulative period and the integrated safety summary were
94.2/100 pt-years, 77.3/100 pt-yrs and 79.2/100 pt-yrs, respectively. The
incidence rates for serious infections in the double-blind period,
five-year cumulative period and the integrated safety summary were 2.1/100
pt-years, 3.0/100 pt-yrs and 3.0/100 pt-yrs, respectively. The incidence
rates for malignancies in the double-blind period, five-year cumulative
period and the integrated safety summary were 2.1/100 pt- years, 1.5/100
pt-yrs and 1.3/100 pt-yrs, respectively. A total of 12 autoimmune
disorders, the most frequent of which were psoriasis and cutaneous
vasculitis, were reported in 12 patients in the cumulative study period.
    During the five-year cumulative period, 32 patients (11.1 percent)
discontinued due to SAEs. A total of five deaths occurred through five
years of the study; all were considered to be unlikely related or unrelated
to study medication.
    About ORENCIA(R) (abatacept)
    ORENCIA is indicated in the United States for reducing signs and
symptoms, inducing major clinical response, inhibiting the progression of
structural damage, and improving physical function in adults with
moderately to severely active rheumatoid arthritis who have had an
inadequate response to one or more DMARDs, such as methotrexate or TNF
antagonists. ORENCIA may be used as monotherapy or concomitantly with
DMARDs other than TNF antagonists. ORENCIA should not be administered
concomitantly with TNF antagonists and is not recommended for use
concomitantly with anakinra.
    Dosing and Administration
    ORENCIA is administered by a healthcare professional as a 30-minute
intravenous infusion at a fixed dose based on body weight range
approximating 10 mg/kg at day 0, 2 weeks, 4 weeks, and every 4 weeks
thereafter. Acute infusion-related reactions were experienced in nine
percent of people treated with ORENCIA and in six percent of people treated
with placebo. According to the full prescribing information, the most
frequently reported infusion- related adverse events (1 percent to 2
percent) were dizziness, headache, and hypertension. In pivotal studies,
premedications were not required. However, appropriate medical support
measures for the treatment of hypersensitivity reactions should be
available for immediate use in the event of a reaction.
    Important Safety Information about ORENCIA(R) (abatacept)
    Before receiving treatment with ORENCIA individuals should tell their
doctor if they are taking a TNF blocker (e.g., Enbrel(R), Humira(R),
Remicade(R)) to treat rheumatoid arthritis (RA). ORENCIA should not be
taken with these medications because of a higher chance of getting a
serious infection. Individuals should also tell their doctor if they are
taking Kineret(R) to treat RA. ORENCIA should not be taken with Kineret.
People taking ORENCIA should notify their doctor if they are taking any
other medications including hormones, over-the-counter medicines, vitamins,
supplements or herbal products.
    Individuals should let their doctor know if they have any kind of
infection including an infection that is in only one place of the body
(such as an open cut or sore) or an infection that is in the whole body
(such as the flu). Having an infection could increase the risk for serious
side effects from ORENCIA. It is also important for individuals to let
their doctor know if they have an infection that won’t go away or a history
of infections that keep coming back.
    People who have had tuberculosis (TB), a positive skin test for TB,
recent close contact with someone who has had TB or develop any of the
symptoms of TB (a dry cough that doesn’t go away, weight loss, fever, night
sweats) should call their doctor right away. Before starting treatment with
ORENCIA, a doctor may examine the individual for TB or perform a skin test.
    In addition, individuals should let their doctor know if they are
scheduled to have surgery or any vaccination or have recently received a
vaccination. People should inform their doctor if they have a history of
chronic obstructive pulmonary (lung) disease (COPD). Taking ORENCIA(R)
(abatacept) may cause COPD symptoms to get worse.
    People who have diabetes and use a blood glucose monitor to check their
sugar levels should tell their doctor. The infusion of ORENCIA contains
maltose, a sugar that can give falsely high blood glucose readings with
some monitors on the day the infusion is received. The doctor may recommend
a different monitor.
    Women who are pregnant, planning to become pregnant or are thinking
about becoming pregnant should tell their doctor. It is not known if
ORENCIA can harm an unborn baby. Women who are breast-feeding should also
inform their doctor. They will need to decide to either breast-feed or
receive treatment with ORENCIA(R) (abatacept), but not both.
    Like all medicines that affect your immune system, ORENCIA can cause
serious side effects. The possible serious side effects include serious
infections and allergic reactions. Also, rare cases of certain kinds of
cancers have been reported.
    People taking ORENCIA are at increased risk for developing infections
including pneumonia, and other infections caused by viruses, bacteria, or
fungi. Individuals should call their doctor immediately if they feel sick
or get any infection during treatment with ORENCIA.
    Allergic reactions are usually mild or moderate, generally occur within
the first 24 hours of an infusion, and include hives, swollen face,
eyelids, lips, tongue, throat, or trouble breathing. There have been some
serious allergic reactions reported in people that received an infusion of
ORENCIA.
    There have been rare cases of certain kinds of cancer in people
receiving ORENCIA. The role of ORENCIA in the development of cancer is not
known. The more common side effects with ORENCIA are headache, upper
respiratory tract infection, sore throat, and nausea.
    For Full Prescribing Information, please visit http://www.ORENCIA.com or
http://www.bms.com
    Bristol-Myers Squibb Company is a global pharmaceutical and related
health care products company whose mission is to extend and enhance human
life.
    * Based on the percentages of patients achieving ACR 20, 50 and 70
responses, indicating 20 percent, 50 percent and 70 percent improvements in
ACR criteria, respectively.