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Bristol-Myers Squibb's ORENCIA® (abatacept) Receives Second European Commission Approval in Less than a Year - New Approval for Treatment of Active Psoriatic Arthritis (PsA)1Bristol-Myers Squibb Company (NYSE: BMY) announced today that the European Commission (EC) has approved ORENCIA alone or in combination with methotrexate for the treatment of active Psoriatic Arthritis (PsA) in adult patients for whom the response to previous disease-modifying antirheumatic drug (DMARD) therapy, including methotrexate, has been inadequate, and additional systemic therapy for psoriatic skin lesions is not required.1 This approval, which allows for the expanded marketing of ORENCIA as a treatment for PsA in all 28 Member States of the EU, marks the second new indication for ORENCIA in less than a year; in September 2016, the European Commission approved ORENCIA, in combination with methotrexate (MTX), for the treatment of highly active and progressive disease in adult patients with rheumatoid arthritis (RA) not previously treated with MTX. PsA becomes the third autoimmune condition, along with rheumatoid arthritis and juvenile idiopathic arthritis, for which ORENCIA is approved to treat in Europe.1 "This EC approval builds on the well-established profile of ORENCIA in Rheumatoid Arthritis and exemplifies our commitment to ongoing clinical research of ORENCIA as a potential treatment for autoimmune conditions where treatment options are limited or where patients have not been helped enough by other medications," said Brian J. Gavin, Ph.D., Vice President, ORENCIA Development Lead at Bristol-Myers Squibb. "Despite the current availability of medications, there are many people with active Psoriatic Arthritis who are in need of a new treatment option; the approval of ORENCIA now provides a novel immunotherapy approach that may help these patients." The approval was based on results from two randomized, double-blind, placebo-controlled studies (Studies PSA-I and PSA-II) in which a higher proportion of patients achieved an ACR 20 response, the primary endpoint, after treatment with ORENCIA 10 mg/kg intravenous (IV) or 125 mg subcutaneous injection (SC) compared to placebo at Week 24: 47.5% versus 19.0% and 39.4% versus 22.3% (p< 0.05), respectively.1 Responses were seen regardless of prior tumor necrosis factor inhibitor (TNFi) treatment in both studies.1 In the phase 3 study, PsA-II, the proportion of radiographic non-progressors (=0 change from baseline) in total PsA-modified SHS on x-rays at Week 24 was greater with ORENCIA 125 mg SC (42.7%) than placebo (32.7% (10.0 [1.0, 19.1] estimate of difference [95% CI]).1 There were no adverse reactions that occurred at = 2% in either treatment group during the 24-week placebo-controlled period. The overall safety profile was comparable between studies PsA-I and PsA-II and consistent with the safety profile in rheumatoid arthritis.1 Headache, upper respiratory tract infection, nasopharyngitis, and nausea were the most commonly reported adverse events occurring at a rate of = 10% in patients taking ORENCIA in the adult RA clinical studies.1 In PsA, the immune system attacks healthy joints and skin.3 T-cell activation is involved in the pathogenesis of PsA.4 The costimulation blockade of ORENCIA inhibits T-cell activation and the resulting cascade of events that contribute to joint destruction. Both IV and SC injection formulations of ORENCIA are now approved to treat adult patients with active PsA.
Additional Information About Studies PSA-I and
PSA-II In PsA-I, 170 patients received placebo or ORENCIA IV at Days 1, 15, 29, and then every 28 days thereafter in a double blind manner for 24 weeks, followed by open-label ORENCIA 10 mg/kg IV every 28 days.1 Patients were randomized to receive placebo or ORENCIA 3 mg/kg, 10 mg/kg (weight range-based dosing: 500 mg for patients weighing less than 60 kg, 750 mg for patients weighing 60 to 100 kg, and 1000 mg for patients weighing greater than 100 kg), or two doses of 30 mg/kg followed by weight range-based dosing of 10 mg/kg without escape for 24 weeks, followed by open label ORENCIA 10 mg/kg monthly IV every month.1 Patients were allowed to receive stable doses of concomitant methotrexate, low dose corticosteroids (equivalent to = 10 mg of prednisone) and/or NSAIDs during the trial. At enrollment, approximately 60% of patients were receiving methotrexate.1 In PsA-II, also known as ASTRAEA, 424 patients were randomized 1:1 to receive weekly doses of SC placebo or ORENCIA 125 mg without a loading dose for 24 weeks, followed by open-label ORENCIA 125 mg SC weekly.1 Patients were allowed to receive stable doses of concomitant methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, low dose corticosteroids (equivalent to = 10 mg of prednisone) and/or NSAIDs during the trial. At randomization, 60.4% of patients were receiving methotrexate.1
About Psoriatic Arthritis U.S. Indications/Usage and Important Safety Information for ORENCIA® (abatacept) Indication and Usage Adult Rheumatoid Arthritis (RA): ORENCIA® (abatacept) is indicated for reducing signs and symptoms, inducing major clinical response, inhibitin the progression of structural damage, and improving physical function in adult patients with moderately to severely active RA. ORENCIA may be used as monotherapy or concomitantly with disease-modifying, anti-rheumatic drugs (DMARDs) other than tumor necrosis factor (TNF) antagonists. Juvenile Idiopathic Arthritis (JIA): ORENCIA® (abatacept) is indicated for reducing signs and symptoms in patients 2 years of age and older with moderately to severely active polyarticular JIA. ORENCIA may be used as monotherapy or concomitantly with methotrexate (MTX). Adult Psoriatic Arthritis (PsA): ORENCIA® (abatacept) is indicated for the treatment of adult patients with active PsA. Important Limitations of Use: ORENCIA should not be administered concomitantly with TNF antagonists, and is not recommended for use concomitantly with other biologic RA therapy, such as anakinra. Important Safety Information for ORENCIA® (abatacept) Concomitant Use with TNF Antagonists: Concurrent therapy with ORENCIA and a TNF antagonist is not recommended. In controlled clinical trials, adult RA patients receiving concomitant intravenous 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: Anaphylaxis or anaphylactoid reactions can occur during or after an infusion and can be life-threatening. There were 2 cases (<0.1%; n=2688) of anaphylaxis or anaphylactoid reactions in clinical trials with adult RA patients treated with intravenous ORENCIA. Other reactions potentially associated with drug hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred in <0.9% of patients. There was one case of a hypersensitivity reaction with ORENCIA in JIA clinical trials (0.5%; n=190). In postmarketing experience, a case of fatal anaphylaxis following the first infusion of ORENCIA was reported. Appropriate medical support measures for treating hypersensitivity reactions should be available for immediate use. If an anaphylactic or other serious allergic reaction occurs, administration of ORENCIA should be stopped immediately and permanently discontinued, with appropriate therapy instituted. Infections: Serious infections, including sepsis and pneumonia, have been reported in patients receiving ORENCIA. Some of these infections have been fatal. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy which, in addition to their underlying disease, could further predispose them to infection. 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. The efficacy of vaccination in patients receiving ORENCIA is not known. ORENCIA 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, including COPD exacerbations, cough, rhonchi, and dyspnea. In adult RA studies, 97% of COPD patients treated with ORENCIA developed adverse reactions versus 88% treated with placebo and respiratory disorders occurred more frequently in patients treated with ORENCIA compared to those on placebo (43% vs 24%, respectively), including COPD exacerbation, cough, rhonchi, and dyspnea. A greater percentage of adult RA 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 for intravenous administration 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 pyrroloquinoline quinone (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. ORENCIA for subcutaneous (SC) administration does not contain maltose; therefore, patients do not need to alter their glucose monitoring. Pregnancy: There are no adequate and well-controlled studies of ORENCIA use in pregnant women and the data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk. A pregnancy registry has been established to monitor pregnancy outcomes in women exposed to ORENCIA during pregnancy. Healthcare professionals are encouraged to register patients by calling 1-877-311-8972. Lactation: There is no information regarding the presence of abatacept in human milk, the effects on the breastfed infant, or the effects on milk production. However, abatacept was present in the milk of lactating rats dosed with abatacept. Most Serious Adverse Reactions: Serious infections (3% ORENCIA vs 1.9% placebo) and malignancies (1.3% ORENCIA vs 1.1% placebo). Malignancies: The overall frequency of malignancies was similar between adult RA patients treated with ORENCIA or placebo. However, more cases of lung cancer were observed in RA 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. Other events reported in =5% of JIA patients were diarrhea, cough, pyrexia, and abdominal pain. In general, the adverse events in JIA and adult PsA patients were similar in frequency and type to those seen in adult RA patients. Note concerning ORENCIA administration options: Intravenous dosing has not been studied in patients younger than 6 years of age. The safety and efficacy of ORENCIA ClickJect™ Autoinjector for subcutaneous injection has not been studied in patients under 18 years of age. 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