WASHINGTON, Nov. 13 /PRNewswire-FirstCall/ -- Bristol-Myers Squibb Company today announced results of the double-blind phase of an ongoing study, which show ORENCIA(R) (abatacept) demonstrated improvement in children with active juvenile idiopathic arthritis (JIA) who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate or TNF antagonists, as measured by the ACR’s Pediatric (ACR Pedi) criteria for improvement of JIA. 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“In this trial of children with active JIA, approximately 53 percent of participants withdrawn from ORENCIA treatment and given placebo experienced disease flares compared to 20 percent of participants continuing to receive ORENCIA,” said Edward H.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 Pediatrics, Division of Rheumatology, Cincinnati Children’s Hospital Medical Center, 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 Pediatrics, Cincinnati Children’s Hospital Medical Center, presented the open-label phase of the study on Sunday, November 12.
Details of Part A of the Trial
In 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), diarrhea (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 Trial
For 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 Arthritis
Juvenile 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.
Important Safety Information about ORENCIA(R) (abatacept)
Before receiving treatment with ORENCIA, individuals should notify their healthcare providers if they currently are receiving treatment with a TNF antagonist (e.g., Enbrel(R), Humira(R), Remicade(R)) or Kineret(R) to treat rheumatoid arthritis (RA). These individuals may have a higher risk of experiencing serious infections if they receive treatment with ORENCIA together with other biologic medications for RA. People receiving treatment with ORENCIA also should notify their healthcare providers if they are taking any other medications including hormones, over-the-counter medicines, vitamins, supplements or herbal products.
Individuals should discuss their risks of infection with their healthcare providers. People should inform their healthcare providers of any infections that they may have, including infections in a specific location in or on the body (such as an open cut or sore), or an infection that involves the whole body (such as the flu), as these types of infection could put individuals at risk for serious side effects from ORENCIA. Additionally, individuals should alert their healthcare providers if they have infections that won’t heal or have histories of recurring infections.
People who have had tuberculosis (TB), have had a positive skin test for TB, or who recently have been in close contact with someone who has had TB should inform their healthcare providers. If these individuals develop any of the symptoms of TB (i.e., a dry cough that doesn’t improve, weight loss, fever, night sweats, etc.), they should notify their healthcare providers immediately. Before initiating treatment with ORENCIA, healthcare providers may examine individuals for TB or perform a skin test to determine the presence of TB.
Additionally, individuals should inform their healthcare providers if they are scheduled to have surgery, or if they recently received a vaccination or are scheduled to receive any vaccinations. Before receiving ORENCIA, people should alert their healthcare providers if they have a history of chronic obstructive pulmonary (lung) disease (COPD), as taking ORENCIA may cause their COPD symptoms to worsen.
Pregnant women, women planning to get pregnant or women thinking about becoming pregnant should inform their healthcare providers prior to starting treatment with ORENCIA(R)(abatacept). It is not known if exposure to ORENCIA poses risks to unborn infants. Women should alert their healthcare providers if they are breastfeeding, as these individuals will need to decide either to breastfeed or to receive treatment with ORENCIA, but not both.
Like all medicines that affect the immune system, ORENCIA can cause serious side effects, including serious infections, allergic reactions and malignancies. Individuals receiving treatment with ORENCIA are at increased risk for developing infections including pneumonia and other infections caused by viruses, bacteria or fungi. Individuals should immediately contact their healthcare providers if they feel sick or experience any infection during treatment with ORENCIA. Allergic reactions to ORENCIA therapy may also occur. These reactions are usually mild or moderate, generally occur within the first 24 hours of an infusion and can include hives, swollen face, eyelids, lips, tongue, throat or difficulty breathing. There have been two serious allergic reactions reported in individuals following ORENCIA infusion. There have also been cases of certain kinds of cancer in individuals receiving ORENCIA. In clinical trials, the frequency of malignancies for ORENCIA was 1.3 percent. 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
Dosing and Administration
ORENCIA is administered 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.
About ORENCIA(R) (abatacept)
ORENCIA is indicated for reducing signs and symptoms, inducing major clinical response, slowing 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.
ORENCIA, a selective modulator of a co-stimulatory signal required for full T-cell activation, was discovered and developed by Bristol-Myers Squibb Company.
Bristol-Myers Squibb is a global pharmaceutical and related health care products company whose mission is to extend and enhance human life.
Bristol-Myers Squibb Company
CONTACT: Media - Sarah Koenig, Phone: +1-609-252-4145, Mobile:+1-908-397-5379, sarah.koenig@bms.com; or Investors - John Elicker, Phone:+1-212-546-3775, john.elicker@bms.com, or Blaine Davis, Phone:+1-212-546-4631, blaine.davis@bms.com
