Healthcare Industry News: Methotrexate
News Release - October 20, 2009
New Data Describe Safety of Subcutaneous Administration of ORENCIA(R) (abatacept) For Patients with Moderate to Severe Rheumatoid ArthritisNEW YORK--(HSMN NewsFeed)--Bristol-Myers Squibb Company (NYSE:BMY ) announced today that new clinical data support continued development of a subcutaneous administration of ORENCIA(R) (abatacept) for patients with moderate to severe rheumatoid arthritis.
Bristol Myers-Squibb has a comprehensive development program underway to evaluate the potential subcutaneous administration of ORENCIA through an injection into the skin in adults with moderate to severe rheumatoid arthritis. ORENCIA is already available for the treatment of adults with moderate to severe rheumatoid arthritis. The subcutaneous program utilizes a new formulation of ORENCIA, which has been specifically designed for subcutaneous administration.
These data, from a 4-month open-label trial involving 100 patients, were presented today at the American College of Rheumatology Annual Scientific Meeting. The study showed that weekly administration of a 125 mg subcutaneous dose of ORENCIA resulted in minimal, transient immunogenicity prior to Month 4 after repeat dosing. The immunogenicity was similar whether ORENCIA was administered in combination with Methotrexate, a common treatment for rheumatoid arthritis, or as a monotherapy. At Month 4, patients had no antibody response to subcutaneous ORENCIA.
“These new data assessing subcutaneous ORENCIA confirm no new safety signal, demonstrate efficacy both in combination with Methotrexate and as monotherapy and show no immunogenicity with the subcutaneous formulation at 4 months,” said Peter T. Nash, M.D., associate professor, Department of Medicine, University of Queensland, Brisbane, Australia.
Of the 100 patients enrolled in the open-label study, 51 received subcutaneous ORENCIA plus Methotrexate and 49 received subcutaneous ORENCIA monotherapy. ORENCIA was self-administered once weekly at a fixed dose of 125 mg in a ready-to-use pre-filled syringe.
The primary objective of the short-term open-label treatment period was to evaluate the immunogenicity of ORENCIA when used with or without Methotrexate in the absence of an IV loading dose of ORENCIA.
Acute injection site reactions were reported in 7 patients (3 patients in the ORENCIA(R) (abatacept) plus Methotrexate cohort and 4 patients in the ORENCIA monotherapy cohort). These reactions did not result in discontinuation of study medication. Five common types of injection site reactions were pre-specified (erythema, pain, pruritus, bruising and swelling). Of these, 2 patients reported injection site pain (1 patient in the ORENCIA plus Methotrexate cohort and 1 patient in the ORENCIA monotherapy cohort) and 4 reported injection site pruritus (3 patients in the ORENCIA plus Methotrexate cohort and 1 patient in the ORENCIA monotherapy cohort). Overall adverse event rates were similar between the subcutaneous ORENCIA plus Methotrexate cohort (72.5%) and the subcutaneous ORENCIA monotherapy cohort (65.3%). There was one serious adverse event considered drug-related in each cohort (Pneumocystis jiroveci pneumonia in the subcutaneous ORENCIA plus Methotrexate cohort and pneumonia in the subcutaneous ORENCIA monotherapy cohort). No malignancies, autoimmune disorders or deaths were reported in the 4 month trial.
ORENCIA is a prescription medicine that is used to treat adults with moderate to severe RA including those who have not been helped enough by other medicines for RA. ORENCIA may prevent further damage to bones and joints, and may help the individual’s ability to perform daily activities. In adults, ORENCIA may be used alone or with disease-modifying anti-rheumatic drugs (DMARDs) other than tumor necrosis factor (TNF) antagonists.
ORENCIA also reduces signs and symptoms in children and adolescents six years of age and older with moderate to severe polyarticular JIA. In children and adolescents, ORENCIA may be used alone or with MTX.
ORENCIA should not be used with TNF antagonists and is not recommended for use with other biologic RA therapy, such as anakinra.
Important Safety Information About ORENCIA
Concomitant Use with TNF antagonists: Concurrent therapy with ORENCIA and a biologic DMARD is not recommended. In controlled clinical trials, adult 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.
Hypersensitivity: Less than 1 percent of adult patients treated with ORENCIA(R) (abatacept) experienced hypersensitivity reactions, including some 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 infusion. There was 1 case of a hypersensitivity reaction with ORENCIA in JIA clinical trials (0.5 percent; n = 190). Appropriate medical support measures for treating hypersensitivity reactions should be available for immediate use in the event of a reaction.
Infections: Caution should be exercised in patients with a history of infection or underlying conditions which may predispose them to infections. Treatment with ORENCIA should be discontinued if a patient develops a serious infection. Patients should be screened for tuberculosis, and viral hepatitis in accordance with published guidelines, and if positive, treated according to standard medical practice prior to therapy with ORENCIA.
Immunizations: Live vaccines should not be given concurrently with ORENCIA or within 3 months of its discontinuation as it may blunt the effectiveness of some immunizations. It is recommended that JIA patients be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating therapy with ORENCIA.
Use in Patients with Chronic Obstructive Pulmonary Disease (COPD): Adult 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 those on placebo (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 those on placebo (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 monitored for worsening of their respiratory status.
Blood Glucose Testing: ORENCIA contains 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, such as those based on glucose dehydrogenase nicotine adenine dinucleotide (GDH-NAD), glucose oxidase, or glucose hexokinase test methods.
Pregnant and Nursing Mothers: ORENCIA(R) (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. A pregnancy registry has been established to monitor fetal outcomes. Healthcare professionals are encouraged to register pregnant patients exposed to ORENCIA by calling 1-877-311-8972.
Most Serious Adverse Reactions: Serious infections (3 percent ORENCIA vs. 1.9 percent placebo) and malignancies (1.3 percent ORENCIA vs. 1.1 percent placebo). In general, adverse events in pediatric and adolescent patients were similar in frequency and type to those seen in adult patients.
Malignancies: The overall frequency of malignancies was similar between adult patients treated with ORENCIA or placebo. However, more cases of lung cancer were observed in patients treated with ORENCIA (0.2 percent) than those on placebo (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.
Most Frequent Adverse Events (=10 percent): Headache, upper respiratory tract infection, nasopharyngitis, and nausea were the most commonly reported adverse events in the adult RA clinical studies.
Please see accompanying Full Prescribing Information, or visit www.ORENCIA.com or www.bms.com.
About Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a systemic,1 chronic, autoimmune disease characterized by inflammation in the lining of joints (or synovium), causing joint damage with chronic pain, stiffness, swelling and fatigue.2 RA causes limited range of motion and decreased function as a result of affected joints losing their shape and alignment.3
RA affects about one percent of the world's population,4 including more than one million people in the United States.1 The condition is more common in women than in men, who account for 75 percent of patients diagnosed with RA.2 ORENCIA(R) (abatacept) is one treatment option indicated in adult patients with moderately to severely active RA. ORENCIA may be used as monotherapy or concomitantly with DMARDs other than TNF antagonists. ORENCIA is not recommended for use concomitantly with other biologic RA therapy, such as anakinra.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 relating to the development and commercialization of certain compounds. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that the clinical trials mentioned in this release will support a regulatory filing. Forward-looking statements in the press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2008, its Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company committed to discovering, developing and delivering innovative medicines that help patients prevail over serious diseases. For more information, please visit www.bms.com.
ORENCIA is a registered trademark of Bristol-Myers Squibb.
1 Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, Liang MH, Kremers HM, Mayes MD, Merkel PA, Pillemer SR, Reveille JD, Stone JH; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008;Jan;58(1):15-25.
2 American College of Rheumatology, Patient Education, Rheumatoid Arthritis. Available at: http://www.rheumatology.org/public/factsheets/ra_new.asp?aud=pat2. Accessed May 2006.
3 National Institute of Arthritis and Musculoskeletal and Skin Diseases. National Institutes of Health. U.S. Department of Health and Human Services. Rheumatoid Arthritis. May 2004.
4 Lee DM, Weinblatt ME. Rheumatoid Arthritis. The Lancet. 2001;358:903-11.
Source: Bristol-Myers Squibb
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