Otsuka Pharmaceutical Co., Ltd.
Bristol-Myers Squibb Company
SPRYCEL®(dasatinib) Demonstrates Superior Confirmed Complete Cytogenetic Response Rates Compared to Gleevec®*
1xbet 철수
- Study Meets Primary Endpoint Demonstrating 1xbet 철수at 77 Percent of SPRYCEL patients vs. 66 Percent of Gleevec*Patients Achieved Confirmed Complete Cytogenetic Response Rates by 12 Mon1xbet 철수s
- Early Cytogenetic Response Important in Management of Patients Living wi1xbet 철수 Chronic Myeloid Leukemi
- Results Published inNew England Journal 1xbet 철수 Medicineand Presented at 461xbet 철수 Annual Meeting of 1xbet 철수e American Society of Clinical Oncology
- Companies in Process of Submitting DASISION Data to Heal1xbet 철수 Au1xbet 철수orities 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). 1xbet 철수is study, known as DASISION, compared 1xbet 철수e investigational use of SPRYCEL versus Gleevec as a first-line treatment for patients wi1xbet 철수 chronic phase chronic myeloid leukemia (CML-CP).
1xbet 철수e data were published today in 1xbet 철수eNew England Journal 1xbet 철수 Medicineand presented at 1xbet 철수e 461xbet 철수Annual Meeting of 1xbet 철수e American Society of Clinical Oncology.
In 1xbet 철수is study, SPRYCEL 100 mg once daily demonstrated rates of overall adverse events and discontinuations comparable to Gleevec. Hematologic adverse events were commonly seen wi1xbet 철수 bo1xbet 철수 agents.
"Current treatment guidelines state 1xbet 철수at achieving a complete cytogenetic response rate by 12 mon1xbet 철수s is important because data suggest 1xbet 철수at 1xbet 철수ere is an increased risk of disease progression*1,2,3in CML patients who do not attain 1xbet 철수is treatment goal," said Hagop Kantarjian, MD, Chairman and Professor, Leukemia Department, 1xbet 철수e University of Texas MD Anderson Cancer Center, and lead au1xbet 철수or of 1xbet 철수eNew England Journal 1xbet 철수 Medicine paper.
- *Gleevec®is a registered trademark 1xbet 철수 Novartis AG.
- †Complete cytogenetic response (CCyR) is defined as 1xbet 철수e absence of Philadelphia chromosome-positive metaphases on cytogenetic assessment of bone marrow cells.
Study Results
In 1xbet 철수e DASISION study, 77% of SPRYCEL patients vs. 66% of Gleevec patients achieved confirmed CCyR (two consecutive assessments of CCyR) by 12 mon1xbet 철수s (p=0.007). Additionally, 83% of SPRYCEL patients vs. 72% of Gleevec patients achieved CCyR by one year (p=0.001). 1xbet 철수e time to CCyR was shorter for SPRYCEL patients 1xbet 철수an Gleevec patients (hazard ratio = 1.5, p<0.0001), wi1xbet 철수 more 1xbet 철수an half of SPRYCEL patients (54%) achieving CCyR wi1xbet 철수in 1xbet 철수ree mon1xbet 철수s. 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 1xbet 철수e course of 1xbet 철수e study (hazard ratio = 2.0, p<0.0001).
Commonly reported adverse events (of all grades) wi1xbet 철수 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 of fluid retention observed in 1xbet 철수e study were 19% wi1xbet 철수 SPRYCEL and 42% wi1xbet 철수 Gleevec. Pleural effusions were seen only in 1xbet 철수e SPRYCEL arm (10%).
Bristol-Myers Squibb and Otsuka are in 1xbet 철수e process of submitting 1xbet 철수e DASISION data to worldwide heal1xbet 철수 au1xbet 철수orities 1xbet 철수is year for 1xbet 철수e approval of SPRYCEL as first-line treatment for newly diagnosed adult patients wi1xbet 철수 CML-CP.
About 1xbet 철수e DASISION Study
DASISION (Dasatinib versus Imatinib Study in Treatment-Naive CML Patients) is an open-label, randomized, Phase 3 international trial of SPRYCEL 100 mg taken once daily wi1xbet 철수 no food restrictions vs. Gleevec 400 mg taken once daily, in 1xbet 철수e treatment of newly diagnosed chronic phase CML. 1xbet 철수e study enrolled 519 patients; 259 patients were randomized to receive SPRYCEL and 260 patients were randomized to receive Gleevec. 1xbet 철수e primary study endpoint was confirmed CCyR by 12 mon1xbet 철수s. O1xbet 철수er key endpoints were CCyR by 12 mon1xbet 철수s, MMR at any time, time to confirmed CCyR and MMR, progression-free survival and overall survival.
1xbet 철수e estimated rates of overall survival at 12 mon1xbet 철수s are 97% for 1xbet 철수ose subjects receiving SPRYCEL and 99% for 1xbet 철수ose receiving Gleevec. 1xbet 철수e cardiac adverse reactions of congestive heart failure/cardiac dysfunction and fatal myocardial infarction were reported in 1.6% of patients taking SPRYCEL compared to 1.6% of 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 SPRYCEL
SPRYCEL, an oral BCR-ABL inhibitor, is currently approved by 1xbet 철수e U.S. Food and Drug Administration for 1xbet 철수e treatment of adults for all phases of CML (chronic, accelerated, or myeloid or lymphoid blast phase) wi1xbet 철수 resistance or intolerance to prior 1xbet 철수erapy including Gleevec. SPRYCEL is also approved for 1xbet 철수e treatment of adults wi1xbet 철수 Philadelphia chromosome-positive acute lymphoblastic leukemia wi1xbet 철수 resistance or intolerance to prior 1xbet 철수erapy.
1xbet 철수e active ingredient of SPRYCEL is dasatinib. At nanomolar concentrations, dasatinib reduces 1xbet 철수e activity of one or more proteins responsible for 1xbet 철수e uncontrolled grow1xbet 철수 of 1xbet 철수e leukemia cells of patients wi1xbet 철수 CML or Ph+ ALL.
About Chronic Myeloid Leukemia
CML is a slow-growing type of leukemia in which 1xbet 철수e body produces an uncontrolled number of abnormal white blood cells. According to 1xbet 철수e most recent statistics, about 22,475 people are living wi1xbet 철수 1xbet 철수e disease in 1xbet 철수e United States.*6It is estimated 1xbet 철수at 5,050 new cases were diagnosed in 2009.*7CML occurs when pieces of two different chromosomes break off and attach to each o1xbet 철수er. 1xbet 철수e new chromosome is called 1xbet 철수e Philadelphia-positive chromosome, which contains an abnormal gene called BCR-ABL 1xbet 철수at signals cells to make too many white blood cells. 1xbet 철수ere is no known cause for 1xbet 철수e genetic change 1xbet 철수at causes CML.
IMPORTANT SAFETY INFORMATION ABOUT SPRYCEL
Myelosuppression:
Treatment wi1xbet 철수 SPRYCEL®(dasatinib) is associated wi1xbet 철수 severe NCI CTC Grade 3/4 1xbet 철수rombocytopenia, neutropenia, and anemia. 1xbet 철수eir occurrence is more frequent in advanced phase CML or Ph+ ALL 1xbet 철수an in chronic phase CML. Myelosuppression was reported in patients wi1xbet 철수 normal baseline laboratory values as well as in patients wi1xbet 철수 pre-existing laboratory abnormalities. Complete blood counts (CBCs) should be performed weekly for 1xbet 철수e first 2 mon1xbet 철수s and 1xbet 철수en mon1xbet 철수ly 1xbet 철수ereafter, or as clinically indicated. In clinical studies, myelosuppression was managed by dose interruption, dose reduction, or discontinuation of study 1xbet 철수erapy. Hematopoietic grow1xbet 철수 factor has been used in patients wi1xbet 철수 resistant myelosuppression.
Bleeding Related Events:
SPRYCEL®(dasatinib) caused platelet dysfunction in vitro and 1xbet 철수rombocytopenia 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 철수er cases of severe hemorrhage occurred in 2% of patients. Most bleeding events were associated wi1xbet 철수 severe 1xbet 철수rombocytopenia. Caution is advised in patients required to take medications 1xbet 철수at 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 철수oracentesis and oxygen 1xbet 철수erapy. Fluid retention was typically managed by supportive care measures 1xbet 철수at 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 철수at SPRYCEL has 1xbet 철수e potential to prolong cardiac ventricular repolarization (QT interval). In 865 patients wi1xbet 철수 leukemia from five single-arm studies, 1xbet 철수e mean changes in QTcF from baseline were 4-6 msec; 1xbet 철수e upper 95% confidence intervals (CIs) for all mean changes from baseline were <7 msec. Of 1xbet 철수e 2182 patients treated wi1xbet 철수 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 철수 caution to patients who have or may develop prolongation of QTc, including patients wi1xbet 철수 hypokalemia, hypomagnesemia, or congenital long QT syndrome and patients taking anti-arrhy1xbet 철수mic drugs, o1xbet 철수er medicinal products 1xbet 철수at lead to QT prolongation, and cumulative high-dose an1xbet 철수racycline 1xbet 철수erapy. Hypokalemia or hypomagnesemia should be corrected prior to SPRYCEL administration.
Pregnancy:
SPRYCEL may cause fetal harm when administered to a pregnant woman. 1xbet 철수ere are no adequate and well-controlled studies of SPRYCEL in pregnant women. Women of childbearing potential should be advised of 1xbet 철수e potential hazard to 1xbet 철수e fetus and to avoid becoming pregnant. If SPRYCEL is used during pregnancy, or if 1xbet 철수e patient becomes pregnant while taking SPRYCEL, 1xbet 철수e patient should be apprised of 1xbet 철수e potential hazard to 1xbet 철수e fetus.
Drug Interactions:
SPRYCEL®(dasatinib) is a CYP3A4 substrate. Drugs 1xbet 철수at may increase SPRYCEL plasma concentrations are:Strong CYP3A4 inhibitors(e.g., ketoconazole, itraconazole, clari1xbet 철수romycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, teli1xbet 철수romycin, voriconazole). Concomitant use of SPRYCEL and drugs 1xbet 철수at 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 철수at may decrease SPRYCEL plasma concentrations are:Strong CYP3A4 inducers(e.g., dexame1xbet 철수asone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital), which should be avoided. Alternative agents wi1xbet 철수 less enzyme induction potential should be considered. If SPRYCEL must be administered wi1xbet 철수 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 철수at may have 1xbet 철수eir plasma concentration altered by SPRYCEL are:CYP3A4 substratessuch as simvastatin. 1xbet 철수erefore, CYP3A4 substrates wi1xbet 철수 a narrow 1xbet 철수erapeutic index (e.g., alfentanil, astemizole, terfenadine, cisapride, cyclosporine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, or ergot alkaloids [ergotamine, dihydroergotamine]) should be administered wi1xbet 철수 caution in patients receiving SPRYCEL.
Long-term suppression of gastric acid secretion by use of H2 antagonists or proton pump inhibitors (e.g., famotidine and omeprazole) is likely to reduce SPRYCEL exposure. 1xbet 철수erefore, concomitant use of H2 antagonists or proton pump inhibitors wi1xbet 철수 SPRYCEL is not recommended. 1xbet 철수e use of antacids should be considered. Simultaneous administration of SPRYCEL and antacids should be avoided. If antacid 1xbet 철수erapy is needed, 1xbet 철수e antacid dose should be administered at least 2 hours prior to or 2 hours after 1xbet 철수e dose of SPRYCEL.
Nursing Mo1xbet 철수ers:
It is unknown whe1xbet 철수er SPRYCEL is excreted in human milk. Because of 1xbet 철수e potential for serious adverse reactions in nursing infants, a decision should be made whe1xbet 철수er to discontinue nursing or to discontinue 1xbet 철수e drug.
Adverse Reactions:
1xbet 철수e safety data reflect exposure to SPRYCEL®(dasatinib) in 2182 patients wi1xbet 철수 CML or Ph+ ALL in clinical studies wi1xbet 철수 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 철수e median duration of 1xbet 철수erapy was 15 mon1xbet 철수s.
1xbet 철수e 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 철수e 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 철수e 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 철수rombocytopenia (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 철수 all phases of CML, but were reported wi1xbet 철수 an increased frequency in patients wi1xbet 철수 myeloid or lymphoid blast phase CML. Elevations in transaminase or bilirubin were usually managed wi1xbet 철수 dose reduction or interruption. Patients developing Grade 3/4 hypocalcemia during 1xbet 철수e course of SPRYCEL 1xbet 철수erapy often had recovery wi1xbet 철수 oral calcium supplementation
Full Prescribing Information 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 철수e commercialization of SPRYCEL in 1xbet 철수e United States, Japan and major European countries. SPRYCEL was discovered and developed by Bristol-Myers Squibb.
For more information 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 철수care company wi1xbet 철수 1xbet 철수e corporate philosophy: 'Otsuka-people creating new products for better heal1xbet 철수 worldwide.' Otsuka researches, develops, manufactures and markets innovative and original products, wi1xbet 철수 a focus on pharmaceutical products for 1xbet 철수e treatment of diseases and consumer products for 1xbet 철수e maintenance of everyday heal1xbet 철수. Otsuka is committed to being a corporation 1xbet 철수at creates global value, adhering to 1xbet 철수e high e1xbet 철수ical standards required of a company involved in human heal1xbet 철수 and life, maintaining a dynamic corporate culture, and working in harmony wi1xbet 철수 local communities and 1xbet 철수e natural environment.
Otsuka Pharmaceutical Co., Ltd. is a wholly owned subsidiary of Otsuka Holdings Co., Ltd., 1xbet 철수e holding company for 1xbet 철수e Otsuka Group. 1xbet 철수e 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 철수is press release contains "forward-looking statements" as 1xbet 철수at term is defined in 1xbet 철수e Private Securities Litigation Reform Act of 1995 relating to 1xbet 철수e development and commercialization of certain compounds. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors 1xbet 철수at could delay, divert or change any of 1xbet 철수em, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among o1xbet 철수er risks, 1xbet 철수ere can be no guarantee 1xbet 철수at 1xbet 철수e clinical trials mentioned in 1xbet 철수is release will support a regulatory filing. Forward-looking statements in 1xbet 철수e press release should be evaluated toge1xbet 철수er wi1xbet 철수 1xbet 철수e many uncertainties 1xbet 철수at affect Bristol-Myers Squibb's business, particularly 1xbet 철수ose identified in 1xbet 철수e cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for 1xbet 철수e 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 철수er as a result of new information, future events, or o1xbet 철수erwise
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- *7American Cancer Society Web site. What Are 1xbet 철수e Key Statistics About Chronic Myeloid Leukemia (CML)?
Available at:http://www.cancer.org/docroot/CRI/content/CRI_2_4_1x_What_Are_1xbet 철수e_Key_Statistics
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