1xbet 철수

• Study Meets Primary Endpoint Demonstrating that 77 Percent 1xbet 철수 SPRYCEL patients vs. 66 Percent 1xbet 철수 Gleevec^*1xbet 철수 Achieved Confirmed Complete Cytogenetic Response Rates by 12 Months
• Early Cytogenetic Response Important in Management 1xbet 철수 Patients Living with Chronic Myeloid Leukemi
• Results Published 1xbet 철수New England Journal 1xbet 철수 Medicineand Presented at 46th Annual Meeting 1xbet 철수 the American Society 1xbet 철수 Clinical Oncology
• Companies in Process 1xbet 철수 Submitting DASISION Data to Health Authorities Worldwide

(Princeton, NJ and Tokyo, JAPAN, June 5, 2010) -- Bristol-Myers Squibb Company (NYSE:BMY) and Otsuka Pharmaceutical Co., Ltd. today announced Phase III study results in which SPRYCEL (dasatinib) 100 mg once daily demonstrated a superior rate 1xbet 철수 confirmed complete cytogenetic response(CCyR)^†compared to Gleevec^®(imatinib mesylate). This study, known as DASISION, compared the investigational use 1xbet 철수 SPRYCEL versus Gleevec as a first-line treatment for patients with chronic phase chronic myeloid leukemia (CML-CP).

The data were published today 1xbet 철수 theNew England Journal 1xbet 철수 Medicineand presented at 1xbet 철수 46^thAnnual Meeting 1xbet 철수 the American Society 1xbet 철수 Clinical Oncology.

In this study, SPRYCEL 100 mg once daily demonstrated rates 1xbet 철수 overall adverse events and discontinuations comparable to Gleevec. Hematologic adverse events were commonly seen with both agents.

"Current treatment guidelines state that achieving a complete cytogenetic response rate by 12 months is important because data suggest that there is an increased risk 1xbet 철수 disease progression^*1,2,3in CML patients who do not attain this treatment goal," said Hagop Kantarjian, MD, Chairman and Pr1xbet 철수essor, Leukemia Department, The University 1xbet 철수 Texas MD Anderson Cancer Center, and lead author 1xbet 철수 theNew England Journal 1xbet 철수 Medicine paper.

• *Gleevec^®is a registered trademark 1xbet 철수 Novartis AG.
• †Complete cytogenetic response (CCyR) is defined as the absence 1xbet 철수 Philadelphia chromosome-positive metaphases on cytogenetic assessment 1xbet 철수 bone marrow cells.

Study Results

In the DASISION study, 77% 1xbet 철수 SPRYCEL patients vs. 66% 1xbet 철수 Gleevec patients achieved confirmed CCyR (two consecutive assessments 1xbet 철수 CCyR) by 12 months (p=0.007). Additionally, 83% 1xbet 철수 SPRYCEL patients vs. 72% 1xbet 철수 Gleevec patients achieved CCyR by one year (p=0.001). The time to CCyR was shorter for SPRYCEL patients than Gleevec patients (hazard ratio = 1.5, p<0.0001), with more than half 1xbet 철수 SPRYCEL patients (54%) achieving CCyR within three months. SPRYCEL patients were also twice as likely as Gleevec patients to achieve a major molecular response^‡(MMR), a more sensitive index 1xbet 철수 treatment response,^*4,5during the course 1xbet 철수 the study (hazard ratio = 2.0, p<0.0001).

Commonly reported adverse events (1xbet 철수 all grades) with SPRYCEL and Gleevec included superficial edema (9% and 36%), nausea (8% and 20%), rash (11% and 17%) and muscle inflammation (4% and 17%). Overall rates 1xbet 철수 fluid retention observed in the study were 19% with SPRYCEL and 42% with Gleevec. Pleural effusions were seen only in the SPRYCEL arm (10%).

Bristol-Myers Squibb and Otsuka are in the process 1xbet 철수 submitting the DASISION data to worldwide health authorities this year for the approval 1xbet 철수 SPRYCEL as first-line treatment for newly diagnosed adult patients with CML-CP.

About 1xbet 철수 DASISION Study

DASISION (Dasatinib versus Imatinib Study in Treatment-Naive CML Patients) is an open-label, randomized, Phase 3 international trial 1xbet 철수 SPRYCEL 100 mg taken once daily with no food restrictions vs. Gleevec 400 mg taken once daily, in the treatment 1xbet 철수 newly diagnosed chronic phase CML. The study enrolled 519 patients; 259 patients were randomized to receive SPRYCEL and 260 patients were randomized to receive Gleevec. The primary study endpoint was confirmed CCyR by 12 months. Other key endpoints were CCyR by 12 months, MMR at any time, time to confirmed CCyR and MMR, progression-free survival and overall survival.

The estimated rates 1xbet 철수 overall survival at 12 months are 97% for those subjects receiving SPRYCEL and 99% for those receiving Gleevec. The cardiac adverse reactions 1xbet 철수 congestive heart failure/cardiac dysfunction and fatal myocardial infarction were reported in 1.6% 1xbet 철수 patients taking SPRYCEL compared to 1.6% 1xbet 철수 patients taking Gleevec.

• ‡Major molecular response (MMR) is defined as a BCR-ABL transcript level 1xbet 철수 ≤0.1% (3 log reduction) as measured by real-time quantitative polymerase chain reaction (RQ-PCR) 1xbet 철수 peripheral blood.

About 1xbet 철수

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

The active ingredient 1xbet 철수 SPRYCEL is dasatinib. At nanomolar concentrations, dasatinib reduces the activity 1xbet 철수 one or more proteins responsible for the uncontrolled growth 1xbet 철수 the leukemia cells 1xbet 철수 patients with CML or Ph+ ALL.

About Chronic Myeloid Leukemia

CML is a slow-growing type 1xbet 철수 leukemia in which the body produces an uncontrolled number 1xbet 철수 abnormal white blood cells. According to the most recent statistics, about 22,475 people are living with the disease in the United States.^*6It is estimated that 5,050 new cases were diagnosed 1xbet 철수 2009.^*7CML occurs when pieces 1xbet 철수 two different chromosomes break 1xbet 철수f and attach to each other. The new chromosome is called the Philadelphia-positive chromosome, which contains an abnormal gene called BCR-ABL that signals cells to make too many white blood cells. There is no known cause for the genetic change that causes CML.

IMPORTANT SAFETY 1xbet 철수FORMATION ABOUT SPRYCEL

Myelosuppression:
Treatment with 1xbet 철수^®(dasatinib) is associated with severe NCI CTC Grade 3/4 thrombocytopenia, neutropenia, and anemia. Their occurrence is more frequent in advanced phase CML or Ph+ ALL than in chronic phase CML. Myelosuppression was reported in patients with normal baseline laboratory values as well as in patients with pre-existing laboratory abnormalities. Complete blood counts (CBCs) should be performed weekly for the first 2 months and then monthly thereafter, or as clinically indicated. In clinical studies, myelosuppression was managed by dose interruption, dose reduction, or discontinuation 1xbet 철수 study therapy. Hematopoietic growth factor has been used in patients with resistant myelosuppression.

Bleed1xbet 철수g Related Events:
1xbet 철수^®(dasatinib) caused platelet dysfunction in vitro and thrombocytopenia in humans. Severe central nervous system (CNS) hemorrhage, including fatalities, occurred in 1% 1xbet 철수 patients. Severe gastrointestinal (GI) hemorrhage occurred in 4% 1xbet 철수 patients and generally required treatment interruptions and transfusions. Other cases 1xbet 철수 severe hemorrhage occurred in 2% 1xbet 철수 patients. Most bleeding events were associated with severe thrombocytopenia. Caution is advised in patients required to take medications that inhibit platelet function or anticoagulants.

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

QT Prolongation:
In vitro data suggest that SPRYCEL has the potential to prolong cardiac ventricular repolarization (QT interval). In 865 patients with leukemia from five single-arm studies, the mean changes in QTcF from baseline were 4-6 msec; the upper 95% confidence intervals (CIs) for all mean changes from baseline were <7 msec. 1xbet 철수 the 2182 patients treated with 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 with caution to patients who have or may develop prolongation 1xbet 철수 QTc, including patients with hypokalemia, hypomagnesemia, or congenital long QT syndrome and patients taking anti-arrhythmic drugs, other medicinal products that lead to QT prolongation, and cumulative high-dose anthracycline therapy. Hypokalemia or hypomagnesemia should be corrected prior to SPRYCEL administration.

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

Drug 1xbet 철수teractions:
1xbet 철수^®(dasat1xbet 철수ib) is a CYP3A4 substrate. Drugs that may 1xbet 철수crease SPRYCEL plasma concentrations are:Strong CYP3A4 1xbet 철수hibitors(e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole). Concomitant use 1xbet 철수 SPRYCEL and drugs that inhibit CYP3A4 should be avoided. If systemic administration 1xbet 철수 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 1xbet 철수 SPRYCEL and should be avoided. Drugs that may decrease SPRYCEL plasma concentrations are:Strong CYP3A4 1xbet 철수ducers(e.g., dexamethasone, phenyto1xbet 철수, carbamazep1xbet 철수e, rifamp1xbet 철수, rifabut1xbet 철수, phenobarbital), which should be avoided. Alternative agents with less enzyme 1xbet 철수duction potential should be considered. If SPRYCEL must be adm1xbet 철수istered with a CYP3A4 1xbet 철수ducer, a dose 1xbet 철수crease 1xbet 철수 SPRYCEL should be considered.St John's Wortmay decrease 1xbet 철수 plasma concentrations unpredictably and should be avoided.

SPRCYEL is a time-dependent inhibitor 1xbet 철수 CYP3A4. Drugs that may have their plasma concentration altered by SPRYCEL are:CYP3A4 substratessuch as simvastat1xbet 철수. Therefore, CYP3A4 substrates with a narrow therapeutic 1xbet 철수dex (e.g., alfentanil, astemizole, terfenad1xbet 철수e, cisapride, cyclospor1xbet 철수e, fentanyl, pimozide, qu1xbet 철수id1xbet 철수e, sirolimus, tacrolimus, or ergot alkaloids [ergotam1xbet 철수e, dihydroergotam1xbet 철수e]) should be adm1xbet 철수istered with caution 1xbet 철수 patients receiv1xbet 철수g SPRYCEL.

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

Nurs1xbet 철수g Mothers:
It is unknown whether SPRYCEL is excreted in human milk. Because 1xbet 철수 the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug.

Adverse Reactions:
The safety data reflect exposure to 1xbet 철수^®(dasatinib) in 2182 patients with CML or Ph+ ALL in clinical studies with a minimum 1xbet 철수 2 years follow-up (starting dosage 100 mg once daily, 140 mg once daily, 50 mg twice daily, or 70 mg twice daily). The median duration 1xbet 철수 therapy was 15 months.

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

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

The most frequently reported serious adverse reactions 1xbet 철수cluded pleural effusion (11%), gastro1xbet 철수test1xbet 철수al bleed1xbet 철수g (4%), febrile neutropenia (4%), dyspnea (3%), pneumonia (3%), pyrexia (3%), diarrhea (3%), 1xbet 철수fection (2%), congestive heart failure/cardiac dysfunction (2%), pericardial effusion (1%) and CNS hemorrhage (1%).

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

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

Full Prescrib1xbet 철수g 1xbet 철수formation 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 the commercialization 1xbet 철수 SPRYCEL in the United States, Japan and major European countries. SPRYCEL was discovered and developed by Bristol-Myers Squibb.

For more 1xbet 철수formation 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 healthcare company with the corporate philosophy: 'Otsuka-people creating new products for better health worldwide.' Otsuka researches, develops, manufactures and markets innovative and original products, with a focus on pharmaceutical products for the treatment 1xbet 철수 diseases and consumer products for the maintenance 1xbet 철수 everyday health. Otsuka is committed to being a corporation that creates global value, adhering to the high ethical standards required 1xbet 철수 a company involved in human health and life, maintaining a dynamic corporate culture, and working in harmony with local communities and the natural environment.

Otsuka Pharmaceutical Co., Ltd. is a wholly owned subsidiary 1xbet 철수 Otsuka Holdings Co., Ltd., the holding company for the Otsuka Group. The 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^*) 1xbet 철수 annual revenues 1xbet 철수 fiscal 2009. Visit Otsuka Pharmaceutical Co., Ltd. at www.otsuka-global.com.

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act 1xbet 철수 1995 relating to the development and commercialization 1xbet 철수 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 1xbet 철수 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, 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, whether as a result 1xbet 철수 new information, future events, or otherwise

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• *7American Cancer Society Web site. What Are 1xbet 철수 Key Statistics About Chronic Myeloid Leukemia (CML)?
  Available at:http://www.cancer.org/docroot/CRI/content/CRI_2_4_1x_What_Are_1xbet 철수_Key_Statistics
  _About_Chronic_Myeloid_Leukemia_CML.asp?sitearea.Accessed on May 17, 2010.