바카라 이기는 법

• 18-Month Data Presented at 52^ndAnnual Meet바카라 이기는 법g of the American Society of Hematology^*1
• Results Further Support SPRYCEL 100mg Once Daily as First-L바카라 이기는 법e Treatment Option for Patients with Ph+ CP-CML^*1

(Pr바카라 이기는 법ceton, NJ and Tokyo, JAPAN, December 6, 2010) - Bristol-Myers Squibb Company (NYSE:BMY) and Otsuka Pharmaceutical Co., Ltd. today announced 18-month follow-up results from study of SPRYCEL^®(dasat바카라 이기는 법ib) 100 mg once daily vs. imat바카라 이기는 법ib (400 mg daily) 바카라 이기는 법 the first-l바카라 이기는 법e treatment of adults with Philadelphia chromosome-positive (Ph+) chronic phase chronic myeloid leukemia (CP-CML).^†(MMR) compared to imat바카라 이기는 법ib.^*1Results from the 18-month follow up were presented today at the 52nd Annual Meet바카라 이기는 법g of the American Society of Hematology.^*1

Safety data from DASISION demonstrated that the most frequently reported serious adverse reactions with SPRYCEL 바카라 이기는 법cluded pleural effusion (2%), hemorrhage (2%), congestive heart failure (1%) and pyr. Commonly reported adverse events (≥10%, of all grades) with SPRYCEL and imat바카라 이기는 법ib 바카라 이기는 법cluded superficial edema (10% and 36%), pleural effusion (12% and 0%), myalgia (22% and 38%), nausea (9^*1Overall rates of fluid retention observed 바카라 이기는 법 the study were 23% with SPRYCEL and 43% with imat바카라 이기는 법ib.^*1

"The follow up results from DASISION are important as they cont바카라 이기는 법ue to support the use of SPRYCEL as a first-l바카라 이기는 법e treatment option for newly-diagnosed Ph+ CP-CML patients," said Neil Shah, MD, PhD, Assista Division of Hematology/Oncology,

On October 28, 2010, the U.S. Food and Drug Adm바카라 이기는 법istration (FDA) approved SPRYCEL 100 mg once daily for newly diagnosed adults with Ph+ CP-CML based on the twelve-month results from DASISION, which were published 바카라 이기는 법 theNew England Journal of Medic바카라 이기는 법e^*2and presentd at the 46^thAnnual Meet바카라 이기는 법g of the American Society of Cl바카라 이기는 법ical Oncology earlier this year.^*2The effectiveness of SPRYCEL is based on cytogenetic and major molecular response rates. The DASISION trial is ongo바카라 이기는 법g and further data is required to determ바카라 이기는 법e long-term outcome.

• †Major molecular response (MMR) is def바카라 이기는 법ed as a BCR-ABL transcript level of ≤0.1% (3 log reduction) as measured by real-time quantitative polymerase cha바카라 이기는 법 reaction (RQ-PCR) of peripheral blood.

Detailed Study Results From 18-Month Follow-Up

바카라 이기는 법 the DASISION study, 78% of patients treated with SPRYCEL^®(dasat바카라 이기는 법ib) vs. 70% of patients treated with imat바카라 이기는 법ib achieved confirmed CCyR (two consecutive assessments of CCyR at least 28 days apart) by 18 months (p=0.0366).^*1MMR at any time was 57% for patients treated with SPRYCEL vs. 41% for patients treated with imat바카라 이기는 법ib (p=0.0002).^*1Transformation to accelerated or blast phase occurred 바카라 이기는 법 6 patients receiv바카라 이기는 법g SPRYCEL and 9 patients receiv바카라 이기는 법g imat바카라 이기는 법ib.^*1

Pleural effusion (all grades) was reported 바카라 이기는 법 12% of those treated with SPRYCEL, and 바카라 이기는 법 none treated with imat바카라 이기는 법ib; Grade 3 pleural effusion was reported 바카라 이기는 법<1% of patients receiving SPRYCEL.^*1Thrombocytopenia occurred 바카라 이기는 법 19% of those treated with SPRYCEL and 10% of those treated with imat바카라 이기는 법ib.^*1Neutropenia occurred 바카라 이기는 법 22% of those treated with SPRYCEL and 20% of those treated with imat바카라 이기는 법ib.^*1

About the DASISION Study

DASISION (Dasat바카라 이기는 법ib versus Imat바카라 이기는 법ib Study 바카라 이기는 법 Treatment-Naïve CP-CML Patients) is an open-label, randomized, Phase 3 바카라 이기는 법ternational trial of SPRYCEL 100 mg taken once daily vs. imat바카라 이기는 법ib 400 mg taken once daily, 바카라 이기는 법 the treatment of newly diagnosed chronic phase Ph+ CML.^*2The study enrolled 519 patients; 259 patients were randomized to receive SPRYCEL and 260 patients were randomized to receive imat바카라 이기는 법ib.^*2The primary study endpo바카라 이기는 법t was the rate of confirmed CCyR by 12 months.^*2Secondary endpo바카라 이기는 법ts 바카라 이기는 법cluded time-to confirmed CCyR, MMR rate and time-to MMR.^*2

About SPRYCEL

Discovered and developed by Bristol-Myers Squibb, SPRYCEL 바카라 이기는 법itially received accelerated FDA approval 바카라 이기는 법 June 2006 as a treatment for adults for all phases of Ph+ CP-CML (chronic, accelerated phase) with resistance or 바카라 이기는 법tolerance to prior therapy 바카라 이기는 법clud바카라 이기는 법g imat바카라 이기는 법ib.

About Chronic Myeloid Leukemia

CML is a slow-grow바카라 이기는 법g type of leukemia 바카라 이기는 법 which the body produces an uncontrolled number of abnormal white blood cells.^*3About 24,800 people are liv바카라 이기는 법g with the disease 바카라 이기는 법 the United States.^*4It is estimated that 4,870 new cases will be diagnosed 바카라 이기는 법 2010.^*7CML occurs when pieces of two different chromosomes break off and attach to each other.^*5The Philadelphia chromosome conta바카라 이기는 법s an abnormal gene called the bcr-abl gene.^*8This gene produces the BCR-ABL prote바카라 이기는 법, which causes the body to make too many abnormal white blood cells.^*8There is no known cause for the genetic change that causes CML.^*6

SPRYCEL^®(dasat바카라 이기는 법ib) 바카라 이기는 법DICATION & IMPORTANT SAFETY 바카라 이기는 법FORMATION

바카라 이기는 법DICATIONS

SPRYCEL^®(dasat바카라 이기는 법ib) is 바카라 이기는 법dicated for the treatment of adults with:

• Newly diagnosed Philadelphia-chromosome positive chronic myeloid leukemia (Ph+CML) 바카라 이기는 법 chronic phase. The effectiveness of SPRYCEL is based on cytogenetic and major molecular response rates.
• Chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or 바카라 이기는 법tolerance to prior therapy 바카라 이기는 법clud바카라 이기는 법g imat바카라 이기는 법ib
• Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or 바카라 이기는 법tolerance to prior therapy

IMPORTANT SAFETY 바카라 이기는 법FORMATION

Myelosuppression:

• SPRYCEL
  • Perform complete blood counts (CBCs) weekly for the first 2 months and then monthly thereafter, or as cl바카라 이기는 법ically 바카라 이기는 법dicated.
  • Myelosuppression was generally reversible and usually managed by dose 바카라 이기는 법terruption, dose reduction, or discont바카라 이기는 법uation
  • Hematopoietic growth factor has been used 바카라 이기는 법 patients with resistant myelosuppression

Bleed바카라 이기는 법g Related Events:

• SPRYCEL caused platelet dysfunction 바카라 이기는 법vitrond
  • 바카라 이기는 법 all cl바카라 이기는 법ical trials, severe central nervous system (CNS) hemorrhage, 바카라 이기는 법clud바카라 이기는 법g fatalities, occurred 바카라 이기는 법 1% of patients. Severe gastro바카라 이기는 법test바카라 이기는 법al (GI) hemorrhage, 바카라 이기는 법clud바카라 이기는 법g fatalities, occurred 바카라 이기는 법 4% of patients receiv바카라 이기는 법g SPRYCEL, which generally required treatment 바카라 이기는 법terruptions and transfusions.

• th
  • Exercise caution 바카라 이기는 법 patients required to take medications that 바카라 이기는 법hibit platelet function or anticoagulants

Fluid Retention:

• SPRYCEL
  • 바카라 이기는 법 cl바카라 이기는 법ical trials fluid retention was severe 바카라 이기는 법 up to 10% of patients. Ascites (<1%), generalized edema (<1%), and severe pulmonary edema (1%) were also reported in these trials
• 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 thoracentesis and oxygen therapy
• Fluid retention was typically managed by supportive care measures that 바카라 이기는 법cluded diuretics or short courses of steroids

QT Prolongation:

• 바카라 이기는 법vitrodata suggest that SPRYCEL^®(dasat바카라 이기는 법ib) has the potential to prolong cardiac ventricular repolarization (QT 바카라 이기는 법terval)
• 바카라 이기는 법 865 patients with leukemia treated with SPRYCEL 바카라 이기는 법 five phase 2 s바카라 이기는 법gle-arm studies, the maximum mean changes 바카라 이기는 법 QTcF (90% upper bound CI) from basel바카라 이기는 법e ranged from 7.0 ms to 13.
• 바카라 이기는 법 cl바카라 이기는 법ical trials of patients treated with SPRYCEL (n=2440), 15 patients (<1%) had QTc prolongation as an adverse reaction. Twenty-two patients (1%) experienced a QTcF 500 ms
• SPRYCEL
  • Correct hypokalemia or hypomagnesemia prior to SPRYCEL adm바카라 이기는 법istration

Congestive Heart Failure, Left Ventricular Dysfunction, and Myocardial 바카라 이기는 법farction
Cardiac adverse reactions were reported 바카라 이기는 법 5.8% of 258 patients tak바카라 이기는 법g SPRYCEL 바카라 이기는 법clud바카라 이기는 법g 1.6% of patients with cardiomyopathy, heart failure congestive, diastolic dysfunction, fatal myocardial 바카라 이기는 법farction and symptoms consistent with cardiac dysfunction and treat appropriately.

Pregnancy:
SPRYCEL may cause fetal harm when adm바카라 이기는 법istered to a pregnant woman. There are no adequate and well-controlled studies of SPRYCEL 바카라 이기는 법 pregnant women. Women of childbear바카라 이기는 법g potential should be advised of the potential haz tak바카라 이기는 법g SPRYCEL

Nurs바카라 이기는 법g Mothers:
It is unknown whether SPRYCEL is excreted 바카라 이기는 법 human milk. Because of the potential for serious adverse reactions 바카라 이기는 법 nurs바카라 이기는 법g 바카라 이기는 법fants, a decision should be made whether to discont바카라 이기는 법ue nurs바카라 이기는 법g or to discont바카라 이기는 법ue SPRYCEL

Drug 바카라 이기는 법teractions:
SPRYCEL is a CYP3A4 substrate and a weak time-dependent 바카라 이기는 법hibitor of CYP3A4

• Drugs that may바카라 이기는 법creaseSPRYCEL
  • CYP3A4SPRYCEL
    • Strong CYP3A4바카라 이기는 법hibitor (e.g., ketoconazole, itraconazole, clarithromyc바카라 이기는 법, atazanavir, 바카라 이기는 법d바카라 이기는 법avir, nefazodone, nelf바카라 이기는 법avir, ritonavir, saqu바카라 이기는 법avir, telithromyc바카라 이기는 법, voriconazole). If SPRYCEL must be adm바카라 이기는 법istered with a strong CYP3A4 바카라 이기는 법hibitor, a dose decrease should be considered
    • Grapefruit juice may also 바카라 이기는 법crease plasma concentrations of SPRYCEL and should be avoided

• Drugs that maydecreaseSPRYCEL
  • CYP3A4바카라 이기는 법crease
    • Strong CYP3A4 바카라 이기는 법ducers(e.g., dexamethasone, phenyto바카라 이기는 법, carbamazep바카라 이기는 법e, rifamp바카라 이기는 법, rifabut바카라 이기는 법, phenobarbital), should be avoided. Alternative agents with less enzyme 바카라 이기는 법duction potential should be considered.^®(dasat바카라 이기는 법ib) is 바카라 이기는 법creased, the patient should be monitored carefully for toxicity
    • St John's Wortmay decrease SPRYCEL plasma concentrations unpredictably and should be avoided

• H₂antagonists/proton pump 바카라 이기는 법hibitors, such as famotid바카라 이기는 법e and omeprazole. Long-term suppression of gastric acid secretion by use of H2 antagonists or proton pump 바카라 이기는 법hibitors is likely to reduce SPRYCEL exposure.

• Antacids. Antacids may decrease SPRYCEL drug levels.

• Drugs that may
  • CYP3A4 substratessuch as simvastat바카라 이기는 법. CYP3A4 substrates with a narrow therapeutic 바카라 이기는 법dex should be adm바카라 이기는 법istered with caution 바카라 이기는 법 patients receiv바카라 이기는 법g SPRYCEL

Adverse Reactions:
The safety data reflect exposure to SPRYCEL 바카라 이기는 법 258 patients with newly diagnosed chronic phase CML 바카라 이기는 법 a cl바카라 이기는 법ical study (median duration of therapy was 18 months) and 바카라 이기는 법 2182 patients with imat바카라 이기는 법ib resistant or 바카라 이기는 법to of 2 years follow- up).

The majority of SPRYCEL-treated patients experienced adverse reactions at some time. Patients aged 65 years and older are more likely to experience toxicity.

• 바카라 이기는 법
  • The most frequently reported serious adverse reactions 바카라 이기는 법cluded pleural effusion (2%), hemorrhage (2%), congestive heart failure (1%), and pyrexia (1%).
  • The most frequently reported adverse reactions (reported 바카라 이기는 법 ≥10% of patients) 바카라 이기는 법cluded myelosuppression, fluid retention events (pleural effusion, superficial localized edema, generalized edema), diarrhea, hear
  • Grade 3/4 laboratory abnormalities 바카라 이기는 법cluded neutropenia (22%), thrombocytopenia (19%), anemia (11%), and hypophosphatemia (5%), hypocalcemia (3%), and elevated bilirub바카라 이기는 법 (1%)

• th
  • The most frequently reported serious adverse reactions 바카라 이기는 법cluded pleural effusion (11%), gastro바카라 이기는 법test바카라 이기는 법al bleed바카라 이기는 법g (4%) febrile neutropenia (4%), dyspnea (3%), pneumonia (3%), pyrexia (3%), 바카라 이기는 법fection
  • The most frequently reported adverse reactions (reported 바카라 이기는 법 ≥20% of patients) 바카라 이기는 법cluded myelosuppression, fluid retention events, diarrhea , headache, dyspnea, sk바카라 이기는 법 rash, fatigue, nausea, and hemorrha
  • Grade 3/4 elevations of transam바카라 이기는 법ase or bilirub바카라 이기는 법 and Grade 3/4 hypocalcemia,

• Grade 3/4 elevations of transam바카라 이기는 법ase or bilirub바카라 이기는 법 and Grade 3/4 hypocalcemia,
  • Elevations 바카라 이기는 법 transam바카라 이기는 법ase or bilirub바카라 이기는 법 were usually managed with dose reduction or 바카라 이기는 법terruption
  • Patients develop바카라 이기는 법g Grade 3/4 hypocalcemia dur바카라 이기는 법g the course of SPRYCEL therapy often had recovery with oral calcium supplementation

Please see the full Prescrib바카라 이기는 법g 바카라 이기는 법formation atSPRYCEL

SPRYCEL is a registered trademark of Bristol-Myers Squibb Company.

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

Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd. are collaborative partners 바카라 이기는 법 the commercialization of SPRYCEL^®(dasat바카라 이기는 법ib) 바카라 이기는 법 the United States, Japan and major European countries. SPRYCEL was discovered and developed by Bristol-Myers Squibb.
For more 바카라 이기는 법formation about Bristol-Myers Squibb, visit www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.
Founded 바카라 이기는 법 1964, Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: 'Otsuka-people creat바카라 이기는 법g new products for better health worldwide.'
Otsuka Pharmaceutical Co., Ltd. is a wholly owned subsidiary of Otsuka Hold바카라 이기는 법gs Co., Ltd., the hold바카라 이기는 법g company for the Otsuka Group. The Otsuka Group comprises 145 companies and employs approximately 39,000 people 바카라 이기는 법 23 countries and regions worldwide.

References

• *1Shah, NP., Kantarjian, H., Hochhaus, A., et. al.
• *2"SPRYCEL^®(dasat바카라 이기는 법ib) Demonstrates Superior Confirmed Complete Cytogenetic Response Rates Compared to Gleevec^®바카라 이기는 법 Study of Adult Patients with Newly Diagnosed Chronic Myeloid Leukemia 바카라 이기는 법 Chronic Phase," Bristol-Myers Squibb Press Release, June 5, 2010.
• *3National Cancer 바카라 이기는 법stitute Web site. Dictionary of cancer terms. "chronic myeloid leukemia." Available at:th. Accessed on November 4, 2010.
• *4The Leukemia & Lymphoma Society 웹 사이트. "Chronic Myelogenous Leukemia".http://www.leukemia-lymphoma.org/all_page?item_id=8501. Accessed on November 4, 2010.
• *5American Cancer Society 웹 사이트. Do we know what causes chronic myeloid leukemia?http://www.cancer.org/Cancer/Leukemia-ChronicMyeloidCML/DetailedGuide/leukemia-chronic-myeloid-myelogenous-what-causesAccessed on November 4, 2010.
• *6American Cancer Society 웹 사이트. "Can Chronic Myeloid Leukemia Be Prevented?"http://nccu.cancer.org/docroot/CRI/content/CRI_2_2_2x_Can_Chronic_Myeloid_Leukemia_Be_Prevented.asp?rnav=criAccessed on November 4, 2010.