FDA Approves Labeling Update for Orencia (abatacept) to Inhibit Structural Joint Damage in Adults with Moderate to Severe Rheumatoid Arthritis
PRINCETON, N.J., (April 25, 2007) -- Bristol-Myers Squibb Company (NYSE: BMY) announced that the U.S. Food and Drug Administration (FDA) has approved an update to the ORENCIA® (abatacept) product labeling regarding the progression of structural joint damage -- an important measure in the treatment of rheumatoid arthritis (RA). The indication was strengthened from “slowing” to “inhibiting” the progression of structural damage in adult patients with moderately to severely active RA who have had an inadequate response to one or more disease-modifying, anti-rheumatic drugs (DMARDs), such as methotrexate (MTX) or tumor necrosis factor (TNF) antagonists.
ORENCIA is indicated 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 RA 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, which was first approved on December 23, 2005, is a selective co-stimulation modulator of a signal required for full T-cell activation and works in a fundamentally different way than cytokine antagonists, including TNF antagonists.
Powerful Data Showed Inhibition of Radiographic
The labeling change is supported by two-year radiographic data from the Phase III AIM (Abatacept in Inadequate responders to MTX) trial, which met the co-primary endpoints of ACR 20 scores at six months, Health Assessment Questionnaire Disability Index (HAQ-DI) scores at one year and joint Erosion Scores (ES) at one year. Fifty-six percent of ORENCIA® (abatacept)/MTX-treated patients had no progression during the first year compared to 45 percent of placebo/MTX-treated patients. In the open-label extension period of the study, 75 percent of patients initially randomized to ORENCIA and MTX and 65 percent of patients initially randomized to placebo and MTX were evaluated radiographically at Year 2. Progression of structural damage in ORENCIA/MTX-treated patients was further reduced in the second year of treatment. Following two years of treatment with ORENCIA/MTX, 51 percent of patients had no progression of structural damage as defined by a change in the Genant-Modified Total Sharp Score (TSS) of zero or less compared with baseline. More than half of patients on ORENCIA had no radiographic progression in either Year 1 or Year 2 (56 percent and 65 percent, respectively).
Improvement Across Clinical Measures
This radiographic impact was consistent with benefits seen in clinical measures of disease activity as assessed by ACR 20, 50 and 70 scores (indicating 20 percent, 50 percent and 70 percent improvement in signs and symptoms of RA, respectively)1, and HAQ-DI (Disability Index of the Health Assessment Questionnaire) in the open-label extension period of the AIM trial.2 These data support the use of ORENCIA in patients with active RA who have had an inadequate response to MTX, and who were continued on their stable dose of MTX.
Concurrent therapy with ORENCIA and a biologic DMARD is not recommended. In controlled clinical trials, patients receiving concomitant ORENCIA and TNF antagonist therapy experienced more infections (63 percent) and serious infections (4.4 percent) compared to patients treated with only TNF antagonists (43 percent and 0.8 percent, respectively), without an important enhancement of efficacy. In clinical trials for ORENCIA, the most serious adverse events were serious infections (3.0 percent of patients treated with ORENCIA and 1.9 percent of patients treated with placebo) and malignancies (1.3 percent of patients treated with ORENCIA and 1.1 percent of patients treated with placebo). The most frequent adverse events occurring in greater than or equal to 10 percent of patients treated with ORENCIA were headache, upper respiratory tract infection nasopharyngitis and nausea.
Important Safety Information about ORENCIA®
Concurrent therapy with ORENCIA and a biologic DMARD is not recommended. In controlled clinical trials, patients receiving concomitant ORENCIA and TNF antagonist therapy experienced more infections (63 percent) and serious infections (4.4 percent) compared to patients treated with only TNF antagonists (43 percent and 0.8 percent, respectively), without an important enhancement of efficacy.
Caution should be exercised in patients with a history of infection or underlying conditions which predispose them to infections. Treatment with ORENCIA should be discontinued if a patient develops a serious infection. Patients should be screened for tuberculosis and, if positive, should be treated according to standard medical practice prior to therapy with ORENCIA.
Less than one percent of patients treated with ORENCIA experienced hypersensitivity reactions, including two cases of anaphylaxis or anaphylactoid reactions. Other events potentially associated with drug hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred in less than 0.9 percent of patients treated with ORENCIA and generally occurred within 24 hours of an infusion with ORENCIA. Appropriate medical support measures for the treatment of hypersensitivity reactions should be available for immediate use in the event of a reaction.
Live vaccines should not be given concurrently with ORENCIA or within three months of its discontinuation.
Chronic Obstructive Pulmonary Disease (COPD) patients treated with ORENCIA developed adverse events more frequently than those treated with placebo (97 percent vs 88 percent, respectively). Respiratory disorders occurred more frequently in patients treated with ORENCIA compared to placebo-treated patients (43 percent vs 24 percent, respectively), including COPD exacerbations, cough, rhonchi, and dyspnea. A greater percentage of patients treated with ORENCIA developed a serious adverse event compared to placebo-treated patients (27 percent vs 6 percent), including COPD exacerbation (3 of 37 patients [8 percent]) and pneumonia (1 of 37 patients [3 percent]). Use of ORENCIA in patients with RA and COPD should be undertaken with caution and such patients should be monitored for worsening of their respiratory status.
Infusions of ORENCIA contain maltose which may result in falsely elevated blood glucose readings on the day of infusion when using blood glucose monitors with test strips utilizing glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ). Consider using monitors and advising patients to use monitors that do not react with maltose.
ORENCIA® (abatacept) should be used during pregnancy only if clearly needed. The risk for development of autoimmune diseases in humans exposed in utero to abatacept has not been determined.
Nursing mothers should be informed of the risk/benefit of continued breast-feeding or discontinuation of the drug.
The most serious adverse reactions were serious infections (3 percent ORENCIA vs 1.9 percent placebo) and malignancies (1.3 percent ORENCIA vs 1.1 percent placebo).
The overall frequency of malignancies was similar in the patients treated with ORENCIA and placebo-treated patients. However, more cases of lung cancer were observed in patients treated with ORENCIA (0.2 percent) than placebo-treated patients (0 percent). A higher rate of lymphoma was seen compared to the general population; however, patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. The potential role of ORENCIA in the development of malignancies in humans is unknown.
The most frequent adverse events occurring in greater than or equal to 10 percent of patients treated with ORENCIA were headache, upper respiratory tract infection, nasopharyngitis, and nausea.
About Rheumatoid Arthritis
Rheumatoid arthritis is a systemic, chronic, autoimmune disease characterized by inflammation in the lining of joints (or synovium), causing joint damage with chronic pain, stiffness, and swelling.3 RA causes limited range of motion and decreased function as a result of affected joints losing their shape and alignment.3
RA affects about 1 percent of the world’s population,4 including more than two million people in the United States.5 In this population, ORENCIA is indicated to treat adults with moderately to severely active RA who have had an inadequate response to one or more DMARDs. RA is more common in women than in men, who account for 75 percent of patients diagnosed.5
The Role of T Cells in Rheumatoid Arthritis
One type of cell found within the immune system is a T cell.6 When T cells are activated, it is thought that they may start a chain of events that leads to the inflammation, pain and joint damage of RA.6 ORENCIA works at the T-cell level, blocking one of the signals of the antigen-presenting cell that causes a T cell to become fully activated,1 thereby helping to modulate the downstream activity of cells such as B cells and macrophages, which are involved in the RA inflammatory cascade.6
This is different than other biologic therapies, which work at the cytokine level of the immune system process.7,8,9,10 Cytokines are a class of proteins that are mostly produced by immune system cells, including T cells.6 Some cytokines are thought to have primary roles in the development of RA.6
For Full Prescribing Information, please visit www.ORENCIA.com or
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1Kremer JM, Westhovens R, Russell A, et al Long-term Efficacy of Abatacept Through 2 Years of Treatment in Rheumatoid Arthritis Patients in the AIM Trial [poster]. Presented at American College of Rheumatology Annual Scientific Meeting; November 10-15, 2006 Washington DC.
2Kremer JM, Emery P, Becker JC, Aranda R, Teng J, Westhovens, R. Abatacept Provides Significant and Sustained Benefits in Clinical and Patient-reported Outcomes Through 2 Years in Patients with Rheumatoid Arthritis and an Inadequate Response to Methotrexate: the Long-term Extension of the AIM Trial [poster]. Presented at European League Against Rheumatism Annual Scientific Meeting: June 21-24, 2006. Amsterdam, The Netherlands.
3Guidelines for the management of rheumatoid arthritis; 2002 update. Arthritis & Rheumatism. 2002;46(2):328-346.
4Lee DM and Weinblatt ME. Rheumatoid arthritis. Lancet. 2001;358:903-911.
5American College of Rheumatology Web site. Rheumatoid arthritis. http://www.rheumatology.org/public/factsheets/ra_new.asp?aud=pat#3 Accessed March 22, 2007.
6Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med. 2001;344:907-916.
7Humira® (adalimumab). Prescribing Information. Abbott Laboratories. North Chicago, IL 60064. February 2007.
8Enbrel® (etanercept). Prescribing Information. Manufactured by Immunex Corporate. Thousand Oaks, CA 91320. Marketed by Amgen and Wyeth Pharmaceuticals Inc. February 2007.
9Remicade® (infliximab). Prescribing Information. Centocor, Inc. Malvern, PA 19355. December 2006.
10Kineret® (anakinra). Prescribing Information. Amgen Inc. Thousand Oaks, CA 91320. December 2006.
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Posted: April 2007