Safety and efficacy data on the investigational subcutaneous formulation of ORENCIA in adults with moderate to severe rheumatoid arthritis to be presented at the American College of Rheumatology Annual Scientific Meeting
NEW YORK--(BUSINESS WIRE)-- Bristol-Myers Squibb Company (NYSE:BMY) announced today that new Phase III clinical data show that a weekly subcutaneous injection of an investigational formulation of ORENCIA® (abatacept), following a single intravenous (I.V.) loading dose, provided an improvement in disease activity similar to the improvement seen with monthly I.V. administration of ORENCIA in patients with moderate to severe rheumatoid arthritis (RA). Improvement in disease activity was measured using the ACR20 criteria (a measurement of RA disease state improvement). The ACQUIRE (Abatacept Comparison of Sub(Qu)cutaneous vs. Intravenous in Inadequate Responders to Methotrexate) trial is a multinational study involving 1,457 patients. ORENCIA has the potential to become the first biologic agent to offer physicians and their appropriate RA patients the flexibility to choose either weekly subcutaneous or monthly I.V. administration. The ACQUIRE results will be presented on November 10 at the American College of Rheumatology (ACR) Annual Scientific Meeting, which is being held in Atlanta from November 6 to 11.
The ACQUIRE trial met the primary endpoint of non-inferiority of subcutaneous to I.V. ORENCIA as measured by ACR20 score at 6 months. At Month 6, 76.1% of patients receiving subcutaneous injections versus 75.7% of patients receiving I.V. infusions achieved ACR20. Serious adverse events occurred in 4.2% of patients in the subcutaneous group and 4.9% of patients in the I.V. group. Of those, serious infections occurred in 0.7% of patients in the subcutaneous group versus 1.4% of patients in the I.V. group (with the most common being pneumonia) and malignancies occurred in 0.4% of patients in the subcutaneous group versus 0.7% of patients in the I.V. group (with the most common being basal cell carcinoma).
“These findings are significant because they demonstrate that subcutaneous ORENCIA may provide an additional administration option for patients and physicians,” said Mark C. Genovese, M.D., professor of medicine and co-chief, Division of Immunology and Rheumatology, Stanford University Medical Center, and lead author of the study. “It is important for patients and physicians to have treatment options when managing RA.”
The primary endpoint of this pivotal, double-blind multinational study was to determine non-inferiority of subcutaneous to I.V. of ORENCIA® (abatacept) by difference in ACR20 response at 6 months. ACR20 is an accepted measure of whether or not a patient achieved at least 20% improvement in RA disease state.1 At Month 6, 76.1% of patients receiving subcutaneous injections versus 75.7% of patients receiving I.V. infusions achieved ACR20, meeting the primary endpoint of non-inferiority of subcutaneous ORENCIA to the I.V. formulation. Secondary endpoints included ACR50 and ACR70 responses, physical function (measured using the Health Assessment Questionnaire Disability Index [HAQ-DI]) and immunogenicity (measured using enzyme-linked immunosorbent assay [ELISA]).
The study included 1,457 patients who have moderately to severely active RA and an inadequate response to methotrexate. Patients were randomized to weekly injections of a 1.0 mL solution containing a 125 mg subcutaneous dose of ORENCIA, with a single I.V. loading dose (~10 mg/kg) on Day 1, or I.V. ORENCIA (~10 mg/kg) on Days 1, 15, 29 and every 4 weeks thereafter, plus methotrexate (a minimum dose of 15 mg/week), for 6 months. To maintain blinding, patients randomized to subcutaneous ORENCIA received placebo I.V. infusions and patients randomized to I.V. ORENCIA received placebo subcutaneous injections. At Month 6, 94.2% of patients receiving subcutaneous injections and 93.8% of patients receiving I.V. ORENCIA remained on treatment.
The proportions of subcutaneous and I.V. patients who achieved a HAQ-DI response (defined as an improvement in HAQ-DI score of ≥0.3 units from baseline) at Month 6 were 69.8% and 65.0%, respectively. Adverse events were reported in 67.0% and 65.2% of patients in the subcutaneous versus I.V. groups, respectively, over 6 months. Serious adverse events were reported in 4.2% and 4.9% of patients in the subcutaneous versus I.V. groups, respectively, over the same time period. Adverse events of particular interest when using biologic therapies, including serious infections, malignancies and pre-specified autoimmune events, occurred in ≤1.4% of patients in the subcutaneous and I.V. groups, with the most common being pneumonia, basal cell carcinoma and psoriasis. Local subcutaneous injection-site reactions occurred in 2.6% of patients receiving subcutaneous ORENCIA® (abatacept) and 2.5% of patients receiving subcutaneous placebo; no patients discontinued due to injection-site reactions. ORENCIA-induced antibodies were observed in 1.1% and 2.3% of subcutaneous and I.V. patients, respectively.
About the ORENCIA® (abatacept) Subcutaneous Development Program
The Phase III development program consists of the pivotal efficacy trial and three supportive safety studies. These supportive studies evaluated safety and efficacy when switching patients from I.V. to subcutaneous ORENCIA therapy (data to be presented at the ACR meeting); immunogenicity, safety and efficacy when withdrawing patients from and re-introducing them to subcutaneous ORENCIA therapy (data to be presented at the ACR meeting); and immunogenicity, safety and efficacy of monotherapy ORENCIA (data presented previously).
About ORENCIA® (abatacept) I.V.
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 antirheumatic 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 juvenile idiopathic arthritis (JIA). In children and adolescents, ORENCIA may be used alone or with methotrexate (MTX).
ORENCIA should not be used with TNF antagonists and is not recommended for use with other biologic RA therapy, such as anakinra.
About Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a systemic,2 chronic, autoimmune disease characterized by inflammation in the lining of joints (or synovium), causing joint damage with chronic pain, stiffness, swelling and fatigue.3 RA causes limited range of motion and decreased function as a result of affected joints losing their shape and alignment.4
RA affects about 1% of the world's population,5 including more than one million people in the United States.2 The condition is more common in women than in men, who account for 75% of patients diagnosed with RA.3 ORENCIA® (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.
Important Safety Information About ORENCIA® (abatacept) I.V.
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%) and serious infections (4.4%) compared to patients treated with only TNF antagonists (43% and 0.8%, respectively), without an important enhancement of efficacy.
Hypersensitivity: Less than 1% of adult patients treated with ORENCIA 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% of patients treated with ORENCIA and generally occurred within 24 hours of infusion. There was one case of a hypersensitivity reaction with ORENCIA in JIA clinical trials (0.5%; 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® (abatacept) developed adverse events more frequently than those treated with placebo (97% vs. 88%, respectively). Respiratory disorders occurred more frequently in patients treated with ORENCIA compared to those on placebo (43% vs. 24%, 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% vs. 6%), including COPD exacerbation [3 of 37 patients (8%)] and pneumonia [1 of 37 patients (3%)]. 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 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 (3.0% ORENCIA vs. 1.9% placebo) and malignancies (1.3% ORENCIA vs. 1.1% 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%) than those on placebo (0%). 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%): Headache, upper respiratory tract infection, nasopharyngitis and nausea were the most commonly reported adverse events in the adult RA clinical studies.
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 regarding product development. 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 subcutaneous formulation of Orencia will receive regulatory approval or, if approved, that it will become a commercially successful product. Forward-looking statements in this 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, 2009, in our Quarterly Reports on Form 10-Q and our 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 whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.
ORENCIA is a registered trademark of Bristol-Myers Squibb.
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2 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.
3 American College of Rheumatology, Practice Management, Rheumatoid Arthritis. Available at: http://www.rheumatology.org/practice/clinical/patients/diseases_and_conditions/ra.asp. Accessed September 2010.
4 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.
5 Lee DM, Weinblatt ME. Rheumatoid Arthritis. The Lancet. 2001;358:903-11.
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