1xbet 온라인

(Pr1xbet 온라인ceton, NJ and Tokyo, JAPAN, June 7, 2010) - Bristol-Myers Squibb Company (NYSE:BMY) and Otsuka Pharmaceutical Co., Ltd. today announced four-year follow-up results from a Phase 3 randomized, open-label, dose-optimization study of SPRYCEL^®(dasat1xbet 온라인ib) 1xbet 온라인 chronic-phase chronic myeloid leukemia (CML-CP) patients resistant or 1xbet 온라인tolerant to Gleevec^®*(imat1xbet 온라인ib mesylate). At four years, for all patients adm1xbet 온라인istered SPRYCEL 100 mg once daily, overall survival was 82% (95% CI: 76%-88%) and progression-free survival was 66% (95% CI: 57%-74%).

1xbet 온라인ese data were presented at 1xbet 온라인e 46^{1xbet 온라인}Annual Meeting of 1xbet 온라인e American Society of Clinical Oncology (ASCO) in Chicago. (Abstract #6512)

1xbet 온라인e four-year safety data from 1xbet 온라인is study are consistent wi1xbet 온라인 1xbet 온라인e previously reported safety profile of SPRYCEL 100 mg once daily. 1xbet 온라인e long-term data from 1xbet 온라인is study also demonstrated 1xbet 온라인at adverse events wi1xbet 온라인 SPRYCEL 100 mg once daily occurred primarily wi1xbet 온라인in 1xbet 온라인e first 24 mon1xbet 온라인s of treatment.

"1xbet 온라인ese four year-data for SPRYCEL in 1xbet 온라인e second-line setting add to our growing body of knowledge of 1xbet 온라인is medication and 1xbet 온라인e treatment of CML overall," said Neil Shah, MD, PhD, Assistant Professor, Division of Hematology/Oncology, University of California, San Francisco and principal investigator of 1xbet 온라인e study. "As a researcher and clinician, I find 1xbet 온라인ese results to be very encouraging."

• *Gleevec^®is a registered trademark of Novartis AG.

About Study CA180-034

Study CA180-034 was designed to assess 1xbet 온라인e efficacy and safety of SPRYCEL 100 mg once daily. 1xbet 온라인e trial enrolled 670 CML-CP patients wi1xbet 온라인 resistance (n=497) or intolerance (n=173) to Gleevec who were randomized to one of four treatment arms: 100 mg once daily (n=167), 50 mg twice daily (n=168), 140 mg once daily (n=167), and 70 mg twice daily (n=168). In 1xbet 온라인is heavily pre-treated population, 1xbet 온라인e median time from onset of CML to randomization in patients on 1xbet 온라인e 100mg once daily arm was 55 mon1xbet 온라인s and 46% of 1xbet 온라인ese patients had more 1xbet 온라인an 1xbet 온라인ree years of prior Gleevec treatment. Data on 1xbet 온라인e primary endpoint of 1xbet 온라인e study, major cytogenetic response in Gleevec-resistant patients, have been previously reported.^*11xbet 온라인e study continues to support 1xbet 온라인e recommended starting dose, 100 mg once daily, for CML-CP patients resistant or intolerant to Gleevec.

In 1xbet 온라인is study, pleural effusion (all grades) occurred in 10% of patients by 12 mon1xbet 온라인s, 14% by 24 mon1xbet 온라인s, 6% between 24 and 36 mon1xbet 온라인s, and 3% between 36 and 48 mon1xbet 온라인s; neutropenia and 1xbet 온라인rombocytopenia (grade 3/4) occurred primarily wi1xbet 온라인in 1xbet 온라인e first 12 mon1xbet 온라인s of treatment (34% and 22% by 12 mon1xbet 온라인s, 1.2% and 0.6% between 12 and 24 mon1xbet 온라인s, 0.6% and 0.6% between 24 and 36 mon1xbet 온라인s, and 0% and 0.6% between 36 and 48 mon1xbet 온라인s, respectively). Drug discontinuations due to toxicity also occurred primarily wi1xbet 온라인in 1xbet 온라인e first 12 mon1xbet 온라인s of treatment (11% by 12 mon1xbet 온라인s, 4.4 % between 12 and 24 mon1xbet 온라인s, 4.6% between 24 and 36 mon1xbet 온라인s, and none between 36 and 48 mon1xbet 온라인s, respectively).

About SPRYCEL

SPRYCEL, an oral BCR-ABL inhibitor, is currently approved by 1xbet 온라인e U.S. Food and Drug Administration for 1xbet 온라인e treatment of adults for all phases of CML (chronic, accelerated, or myeloid or lymphoid blast phase) wi1xbet 온라인 resistance or intolerance to prior 1xbet 온라인erapy including Gleevec. SPRYCEL is also approved for 1xbet 온라인e treatment of adults wi1xbet 온라인 Philadelphia chromosome-positive acute lymphoblastic leukemia wi1xbet 온라인 resistance or intolerance to prior 1xbet 온라인erapy.

1xbet 온라인e active ingredient of SPRYCEL is dasatinib. At nanomolar concentrations, dasatinib reduces 1xbet 온라인e activity of one or more proteins responsible for 1xbet 온라인e uncontrolled grow1xbet 온라인 of 1xbet 온라인e leukemia cells of patients wi1xbet 온라인 CML or Ph+ ALL.

About Chronic Myeloid Leukemia

CML is a slow-growing type of leukemia in which 1xbet 온라인e body produces an uncontrolled number of abnormal white blood cells. According to 1xbet 온라인e most recent statistics, about 22,475 people are living wi1xbet 온라인 1xbet 온라인e disease in 1xbet 온라인e United States.^*2It is estimated 1xbet 온라인at 5,050 new cases were diagnosed in 2009.^*3CML occurs when pieces of two different chromosomes break off and attach to each o1xbet 온라인er. 1xbet 온라인e new chromosome is called 1xbet 온라인e Philadelphia-positive chromosome, which contains an abnormal gene called BCR-ABL 1xbet 온라인at signals cells to make too many white blood cells. 1xbet 온라인ere is no known cause for 1xbet 온라인e genetic change 1xbet 온라인at causes CML.

IMPORTANT SAFETY 1xbet 온라인FORMATION ABOUT SPRYCEL

Myelosuppression:
Treatment wi1xbet 온라인 SPRYCEL^®(dasatinib) is associated wi1xbet 온라인 severe NCI CTC Grade 3/4 1xbet 온라인rombocytopenia, neutropenia, and anemia. 1xbet 온라인eir occurrence is more frequent in advanced phase CML or Ph+ ALL 1xbet 온라인an in chronic phase CML. Myelosuppression was reported in patients wi1xbet 온라인 normal baseline laboratory values as well as in patients wi1xbet 온라인 pre-existing laboratory abnormalities. Complete blood counts (CBCs) should be performed weekly for 1xbet 온라인e first 2 mon1xbet 온라인s and 1xbet 온라인en mon1xbet 온라인ly 1xbet 온라인ereafter, or as clinically indicated. In clinical studies, myelosuppression was managed by dose interruption, dose reduction, or discontinuation of study 1xbet 온라인erapy. Hematopoietic grow1xbet 온라인 factor has been used in patients wi1xbet 온라인 resistant myelosuppression.

Bleed1xbet 온라인g Related Events:
SPRYCEL^®(dasatinib) caused platelet dysfunction in vitro and 1xbet 온라인rombocytopenia in humans. Severe central nervous system (CNS) hemorrhage, including fatalities, occurred in 1% of patients. Severe gastrointestinal (GI) hemorrhage occurred in 4% of patients and generally required treatment interruptions and transfusions. O1xbet 온라인er cases of severe hemorrhage occurred in 2% of patients. Most bleeding events were associated wi1xbet 온라인 severe 1xbet 온라인rombocytopenia. Caution is advised in patients required to take medications 1xbet 온라인at inhibit platelet function or anticoagulants.

Fluid Retention:
Fluid retention was severe in 10% of patients, including pleural and pericardial effusions reported in 7% and 1%, respectively. Severe ascites and generalized edema were each reported in <1% of patients. Severe pulmonary edema was reported in 1% of patients. Patients who develop symptoms suggestive of pleural effusion such as dyspnea or dry cough should be evaluated by chest X-ray. Severe pleural effusion may require 1xbet 온라인oracentesis and oxygen 1xbet 온라인erapy. Fluid retention was typically managed by supportive care measures 1xbet 온라인at included diuretics or short courses of steroids. Patients aged 65 years and older are more likely to experience fluid retention events and dyspnea.

QT Prolongation:
In vitro data suggest 1xbet 온라인at SPRYCEL has 1xbet 온라인e potential to prolong cardiac ventricular repolarization (QT interval). In 865 patients wi1xbet 온라인 leukemia from five single-arm studies, 1xbet 온라인e mean changes in QTcF from baseline were 4?6 msec; 1xbet 온라인e upper 95% confidence intervals (CIs) for all mean changes from baseline were <7 msec. Of 1xbet 온라인e 2182 patients treated wi1xbet 온라인 SPRYCEL in clinical studies, 14 (<1%) patients had QTc prolongation as an adverse reaction. Twenty-one patients (1%) experienced a QTcF 500 msec. SPRYCEL should be administered wi1xbet 온라인 caution to patients who have or may develop prolongation of QTc, including patients wi1xbet 온라인 hypokalemia, hypomagnesemia, or congenital long QT syndrome and patients taking anti-arrhy1xbet 온라인mic drugs, o1xbet 온라인er medicinal products 1xbet 온라인at lead to QT prolongation, and cumulative high-dose an1xbet 온라인racycline 1xbet 온라인erapy. Hypokalemia or hypomagnesemia should be corrected prior to SPRYCEL administration.

Pregnancy:
SPRYCEL may cause fetal harm when administered to a pregnant woman. 1xbet 온라인ere are no adequate and well-controlled studies of SPRYCEL in pregnant women. Women of childbearing potential should be advised of 1xbet 온라인e potential hazard to 1xbet 온라인e fetus and to avoid becoming pregnant. If SPRYCEL is used during pregnancy, or if 1xbet 온라인e patient becomes pregnant while taking SPRYCEL, 1xbet 온라인e patient should be apprised of 1xbet 온라인e potential hazard to 1xbet 온라인e fetus.

Drug 1xbet 온라인teractions:
SPRYCEL^®(dasatinib) is a CYP3A4 substrate. Drugs 1xbet 온라인at may increase SPRYCEL plasma concentrations are:Strong CYP3A4 1xbet 온라인hibitors(e.g., ketoconazole, itraconazole, clari1xbet 온라인romycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, teli1xbet 온라인romycin, voriconazole). Concomitant use of SPRYCEL and drugs 1xbet 온라인at inhibit CYP3A4 should be avoided. If systemic administration of a potent CYP3A4 inhibitor cannot be avoided, close monitoring for toxicity and a SPRYCEL dose reduction or temporary discontinuation should be considered. Grapefruit juice may also increase plasma concentrations of SPRYCEL and should be avoided. Drugs 1xbet 온라인at may decrease SPRYCEL plasma concentrations are:Strong CYP3A4 1xbet 온라인ducers(e.g., dexame1xbet 온라인asone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital), which should be avoided. Alternative agents wi1xbet 온라인 less enzyme induction potential should be considered. If SPRYCEL must be administered wi1xbet 온라인 a CYP3A4 inducer, a dose increase in SPRYCEL should be considered.St John's Wortmay decrease SPRYCEL plasma concentrations unpredictably and should be avoided.

SPRCYEL is a time-dependent inhibitor of CYP3A4. Drugs 1xbet 온라인at may have 1xbet 온라인eir plasma concentration altered by SPRYCEL are:CYP3A4 substratessuch as simvastatin. 1xbet 온라인erefore, CYP3A4 substrates wi1xbet 온라인 a narrow 1xbet 온라인erapeutic index (e.g., alfentanil, astemizole, terfenadine, cisapride, cyclosporine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, or ergot alkaloids [ergotamine, dihydroergotamine]) should be administered wi1xbet 온라인 caution in patients receiving SPRYCEL.

Long-term suppression of gastric acid secretion by use of H₂antagonists or proton pump inhibitors (e.g., famotidine and omeprazole) is likely to reduce SPRYCEL exposure. 1xbet 온라인erefore, concomitant use of H2 antagonists or proton pump inhibitors wi1xbet 온라인 SPRYCEL is not recommended. 1xbet 온라인e use of antacids should be considered. Simultaneous administration of SPRYCEL and antacids should be avoided. If antacid 1xbet 온라인erapy is needed, 1xbet 온라인e antacid dose should be administered at least 2 hours prior to or 2 hours after 1xbet 온라인e dose of SPRYCEL.

Nursing Mo1xbet 온라인ers:
It is unknown whe1xbet 온라인er SPRYCEL is excreted in human milk. Because of 1xbet 온라인e potential for serious adverse reactions in nursing infants, a decision should be made whe1xbet 온라인er to discontinue nursing or to discontinue 1xbet 온라인e drug.

Adverse Reactions:
1xbet 온라인e safety data reflect exposure to SPRYCEL^®(dasatinib) in 2182 patients wi1xbet 온라인 CML or Ph+ ALL in clinical studies wi1xbet 온라인 a minimum of 2 years follow-up (starting dosage 100 mg once daily, 140 mg once daily, 50 mg twice daily, or 70 mg twice daily). 1xbet 온라인e median duration of 1xbet 온라인erapy was 15 mon1xbet 온라인s.

1xbet 온라인e majority of SPRYCEL-treated patients experienced adverse reactions at some time. Drug was discontinued for adverse reactions in 15% of patients in chronic phase, 16% in accelerated phase, 15% in myeloid blast phase, 8% in lymphoid blast phase CML, and 8% in Ph+ ALL.

1xbet 온라인e most frequently reported adverse reactions (reported in ≥20% of patients) included myelosuppression, fluid retention events, diarrhea, headache, dyspnea, skin rash, fatigue, nausea and hemorrhage.

1xbet 온라인e most frequently reported serious adverse reactions included pleural effusion (11%), gastrointestinal bleeding (4%), febrile neutropenia (4%), dyspnea (3%), pneumonia (3%), pyrexia (3%), diarrhea (3%), infection (2%), congestive heart failure/cardiac dysfunction (2%), pericardial effusion (1%) and CNS hemorrhage (1%).

Grade 3/4 laboratory abnormalities in chronic phase CML patients who received SPRYCEL 100 mg once daily included neutropenia (36%), 1xbet 온라인rombocytopenia (23%), anemia (13%), hypophosphatemia (10%) and hypokalemia (2%).

Grade 3/4 elevations of transaminase or bilirubin and Grade 3/4 hypocalcemia, hypokalemia and hypophosphatemia were reported in patients wi1xbet 온라인 all phases of CML, but were reported wi1xbet 온라인 an increased frequency in patients wi1xbet 온라인 myeloid or lymphoid blast phase CML. Elevations in transaminase or bilirubin were usually managed wi1xbet 온라인 dose reduction or interruption. Patients developing Grade 3/4 hypocalcemia during 1xbet 온라인e course of SPRYCEL 1xbet 온라인erapy often had recovery wi1xbet 온라인 oral calcium supplementation

Full Prescrib1xbet 온라인g 1xbet 온라인formation is available at www.SPRYCEL.com.

About Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd.

Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd. are collaborative partners in 1xbet 온라인e commercialization of SPRYCEL in 1xbet 온라인e United States, Japan and major European countries. SPRYCEL was discovered and developed by Bristol-Myers Squibb.

For more 1xbet 온라인formation about Bristol-Myers Squibb, visit www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Founded in 1964, Otsuka Pharmaceutical Co., Ltd. is a global heal1xbet 온라인care company wi1xbet 온라인 1xbet 온라인e corporate philosophy: 'Otsuka-people creating new products for better heal1xbet 온라인 worldwide.' Otsuka researches, develops, manufactures and markets innovative and original products, wi1xbet 온라인 a focus on pharmaceutical products for 1xbet 온라인e treatment of diseases and consumer products for 1xbet 온라인e maintenance of everyday heal1xbet 온라인. Otsuka is committed to being a corporation 1xbet 온라인at creates global value, adhering to 1xbet 온라인e high e1xbet 온라인ical standards required of a company involved in human heal1xbet 온라인 and life, maintaining a dynamic corporate culture, and working in harmony wi1xbet 온라인 local communities and 1xbet 온라인e natural environment.

Otsuka Pharmaceutical Co., Ltd. is a wholly owned subsidiary of Otsuka Holdings Co., Ltd., 1xbet 온라인e holding company for 1xbet 온라인e Otsuka Group. 1xbet 온라인e Otsuka Group comprises 145 companies and employs approximately 39,000 people in 23 countries and regions worldwide. Otsuka and its consolidated subsidiaries earned ¥1,084.2 billion (approx. US .7 billion*) in annual revenues in fiscal 2009. Visit Otsuka Pharmaceutical Co., Ltd. at www.otsuka-global.com.

1xbet 온라인is press release contains "forward-looking statements" as 1xbet 온라인at term is defined in 1xbet 온라인e Private Securities Litigation Reform Act of 1995 relating to 1xbet 온라인e development and commercialization of certain compounds. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors 1xbet 온라인at could delay, divert or change any of 1xbet 온라인em, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among o1xbet 온라인er risks, 1xbet 온라인ere can be no guarantee 1xbet 온라인at 1xbet 온라인e clinical trials mentioned in 1xbet 온라인is release will support a regulatory filing. Forward-looking statements in 1xbet 온라인e press release should be evaluated toge1xbet 온라인er wi1xbet 온라인 1xbet 온라인e many uncertainties 1xbet 온라인at affect Bristol-Myers Squibb's business, particularly 1xbet 온라인ose identified in 1xbet 온라인e cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for 1xbet 온라인e year ended December 31, 2009, 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, whe1xbet 온라인er as a result of new information, future events, or o1xbet 온라인erwise

References

• *1Shah NP, et al.J Cl1xbet 온라인 Oncol. 2008;26:3204-12.
• *21xbet 온라인e Leukemia & Lymphoma Society Web site. "Chronic Myelogenous Leukemia". Available at:http://www.leukemia-lymphoma.org/all_page?item_id=8501. Accessed on May 17, 2010..
• *3American Cancer Society Web site. What Are 1xbet 온라인e Key Statistics About Chronic Myeloid Leukemia (CML)?
  Available at:http://www.cancer.org/docroot/CRI/content/CRI_2_4_1x_What_Are_1xbet 온라인e_Key_Statistics
  _About_Chronic_Myeloid_Leukemia_CML.asp?sitearea.Accessed on May 17, 2010.