ORENCIA(R) (abatacept) Data Demonstrated Improvement in Children and Adolescents With Juvenile Idiopathic Arthritis as Measured by the Validated ACR Paediatric Criteria

In addition, no child receiving ORENCIA during the six-month double-blind phase had a serious adverse event (SAE) or discontinued due to an adverse event (AE). The data were presented today at a late-breaking session of the 2006 American College of Rheumatology (ACR) Annual Scientific Meeting.

The study, designed to assess the efficacy and safety of ORENCIA in children and adolescents (ages 6-17 years) with a mean age of 12.4 years with JIA, consists of three phases: a four-month treatment period in which all participants received ORENCIA and response was assessed (Part A), a six-month randomized double-blind phase where responders received either ORENCIA or placebo (Part B) and an open-label phase designed to assess long-term safety and efficacy (Part C). Results from Part A were presented at an ACR Concurrent Abstract Session on Sunday, November 12; findings from the double- blind phase (Part B) were presented at a late-breaking data presentation at ACR today."In this trial of children with active JIA, approximately 53 percent of participants withdrawn from ORENCIA treatment and given placebo experienced disease flares compared to 20 percent of participants continuing to receive ORENCIA," said Edward H. Giannini, M.Sc., Dr.P.H., Professor of Paediatrics, Division of Rheumatology, Cincinnati Children's Hospital Medical Centre, OH, co-principal investigator of the study and presenter of the late-breaker data from the double-blind placebo phase of the study. Co-principal investigator Daniel J. Lovell, M.D., M.P.H., Professor of Paediatrics, Cincinnati Children's Hospital Medical Centre, presented the open-label phase of the study on Sunday, November 12.Details of Part A of the TrialIn the initial four-month phase of the trial, 190 children and adolescents with JIA, 72 percent of whom were female, who had inadequately responded to one or more DMARDs received ORENCIA (10 mg/kg IV; maximum 1,000 mg). Of the 190 participants, 28 percent previously had failed one or more biologic DMARDs. Seventy-four percent were on methotrexate (MTX) at study start and continued to receive MTX throughout the study (mean dosage was 13.2 mg/m2/week). Participants discontinued any DMARD other than MTX prior to the first dose of study medication.The participants were evaluated using the ACR's validated scale for the assessment of improvement of JRA/JIA (ACR Pedi). Of the 190 participants, 123 (64.7 percent) had an ACR Pedi 30 response; 49.5 percent had an ACR Pedi 50 response and 28.4 percent had an ACR Pedi 70 response.Of the six SAEs reported during Part A of the study, three were related to JIA (flare and arthropathy). The remaining three were varicella, ovarian cyst and acute lymphocytic leukemia. All SAEs were considered by the investigators to be unlikely related to or unrelated to study medication. Adverse events (AEs) were reported in 70 percent of participants. Those reported in greater than or equal to 5 percent of participants included headache (13 percent), nausea (10 percent), cough (9 percent), diarrhoea (9 percent), upper respiratory tract infection (7 percent), pyrexia (6 percent), nasopharyngitis (6 percent) and upper abdominal pain (5 percent).Details of Part B of the TrialFor the second phase of the study, 122 of the 123 participants who achieved an ACR Pedi 30 response in the first phase were randomized in a 1:1 ratio to receive double-blind therapy with either ORENCIA or placebo every 28 days for up to six months. The primary objective of the study was time to disease flare. Forty-eight patients in the ORENCIA group and 46 in the placebo group received concomitant MTX therapy. The mean dosage of MTX was 13.5 mg/m2/week for the ORENCIA group and 12.9 mg/m2/week for the placebo group. Approximately 70 percent of both the ORENCIA and placebo groups were female. Those who experienced disease flares during the trial were offered open-label ORENCIA therapy in Part C of the trial. Safety assessments were performed at each visit. Of the 122 participants, a total of 33 out of 62 (53.2 percent) of the children receiving placebo experienced disease flares compared to 12 out of 60 (20 percent) receiving ORENCIA.Two of the participants receiving placebo experienced SAEs: one case of hematoma and one case of both varicella and encephalitis; neither child discontinued participation in the trial. No child receiving ORENCIA during the six-month double-blind phase had an SAE.Adverse events were reported in 61.7 percent (n=36) of participants treated with ORENCIA and 54.8 percent (n=34) of participants receiving placebo. Those occurring in greater than or equal to 3.5 percent in the ORENCIA and placebo groups, respectively, included: - Influenza: 8.3 percent (n=5) and 6.5 percent (n=4) - Bacteriuria: 6.7 percent (n=4) and 0 percent - Nasopharyngitis: 6.7 percent (n=4) and 4.8 percent (n=3) - Pyrexia: 6.7 percent (n=4) and 8.1 percent (n=5) - Upper respiratory tract infection: 6.7 percent (n=4) and 8.1 percent (n=5) - Abdominal pain: 5 percent (n=3) and 1.6 percent (n=1) - Gastroenteritis: 5 percent (n=3) and 1.6 percent (n=1) - Headache: 5 percent (n=3) and 1.6 percent (n=1) - Sinusitis: 5 percent (n=3) and 3.2 percent (n=2) - Nausea: 3.3 percent (n=2) and 6.5 percent (n=4) - Rhinitis: 1.7 percent (n=1) and 6.5 percent (n=4) Infusional AEs occurred in two participants from each group. About Juvenile Idiopathic ArthritisJuvenile idiopathic arthritis (JIA) -- also commonly known as juvenile rheumatoid arthritis (JRA) -- is a chronic, autoimmune disease, causing chronic pain, stiffness and swelling of the joints, which may ultimately lead to joint damage and deformities. The disease begins before the age of 16 and affects about 1 child in every 1,000 in the United States. Despite current therapies, some individuals with JIA experience ongoing disease and many eventually worsen, resulting in severe joint damage and abnormal joint function.(Source: Annual Scientific Meeting: American College of Rheumatology : November 2006.)