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European Medicines Agency Validates Application for Bristol-Myers Squibb's Sprycel (dasatinib) in Children with Chronic Myelogenous LeukemiaBristol-Myers Squibb Company (NYSE:BMY) today announced that the European Medicines Agency (EMA (News - Alert)) validated its grouped Type II variation/Extension of Application for Sprycel (dasatinib) to treat children and adolescents aged 1 year to 18 years with chronic phase Philadelphia chromosome positive chronic myelogenous leukemia (CML) and to include the powder for oral suspension. Validation of the application confirms the submission is complete and begins the EMA's centralized review process. "Treatment options for pediatric patients with chronic phase CML, along with formulations that support the unique demands of children with cancer continue to be unmet needs," said Murdo Gordon, executive vice president and chief commercial officer, Bristol-Myers Squibb. "Building on our long-standing heritage in hematology, including the use of Sprycel for more than a decade to treat adults with certain forms of CML, the validation of this application supports our commitment to expand options for children and adolescents with different types of cancer." The application includes data from CA180-226 (NCT00777036), an ongoing Phase 2, open-label, non-randomized trial studying Sprycel in newly diagnosed chronic phase CML pediatric patients and in pediatric patients resistant to or intolerant of imatinib. Data from this study will be presented at the American Society of Clinical Oncology Annual Meeting 2017 in Chicago on Monday, June 5. About Sprycel Sprycel was first approved by the FDA in 2006 for the treatment of adults with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP) who are resistant or intolerant to prior therapy including imatinib. At that time, Sprycel was also approved for adults with Ph+ acute lymphoblastic leukemia (ALL) who are resistant or intolerant to prior therapy. Sprycel is approved and marketed worldwide for these indications in more than 60 countries. Sprycel is also an FDA-approved treatment for adults with newly diagnosed CP Ph+ CML (since October 2010). Sprycel received accelerated FDA approval for this indication. Additional country approvals for this indication total more than 50. U.S. FDA-APPROVED INDICATIONS FOR SPRYCEL® SPRYCEL® (dasatinib) is indicated for the treatment of adults with:
IMPORTANT SAFETY INFORMATION Myelosuppression Treatment with SPRYCEL is associated with severe (NCI CTC (News - Alert) Grade 3/4) thrombocytopenia, neutropenia, and anemia, which occur earlier and more frequently in patients with advanced phase CML or Ph+ ALL than in patients with chronic phase CML. Myelosuppression was reported in patients with normal baseline laboratory values as well as in patients with pre-existing laboratory abnormalities.
Bleeding-Related Events SPRYCEL caused thrombocytopenia in human subjects. In addition, dasatinib caused platelet dysfunction in vitro. In all CML or Ph+ ALL clinical studies, =grade 3 central nervous system (CNS) hemorrhages, including fatalities, occurred in <1% of patients receiving SPRYCEL. Grade 3 or greater gastrointestinal hemorrhage, including fatalities, occurred in 4% of patients and generally required treatment interruptions and transfusions. Other cases of =grade 3 hemorrhage occurred in 2% of patients.
Fluid Retention SPRYCEL may cause fluid retention. After 5 years of follow-up in the randomized newly diagnosed chronic phase CML study (n=258), grade 3/4 fluid retention was reported in 5% of patients, including 3% of patients with grade 3/4 pleural effusion. In patients with newly diagnosed or imatinib resistant or intolerant chronic phase CML, grade 3/4 fluid retention occurred in 6% of patients treated with SPRYCEL at the recommended dose (n=548). In patients with advanced phase CML or Ph+ ALL treated with SPRYCEL at the recommended dose (n=304), grade 3/4 fluid retention was reported in 8% of patients, including grade 3/4 pleural effusion reported in 7% of patients.
Cardiovascular Events After 5 years of follow-up in the randomized newly diagnosed chronic phase CML trial (n=258), the following cardiac adverse events occurred:
Monitor patients for signs or symptoms consistent with cardiac dysfunction and treat appropriately. Pulmonary Arterial Hypertension (PAH) SPRYCEL may increase the risk of developing PAH, which may occur any time after initiation, including after more than 1 year of treatment. Manifestations include dyspnea, fatigue, hypoxia, and fluid retention. PAH may be reversible on discontinuation of SPRYCEL.
QT Prolongation In vitro data suggest that dasatinib has the potential to prolong cardiac ventricular repolarization (QT interval).
Severe Dermatologic Reactions Cases of severe mucocutaneous dermatologic reactions, including Stevens-Johnson syndrome and erythema multiforme, have been reported in patients treated with SPRYCEL.
Tumor Lysis Syndrome (TLS) TLS has been reported in patients with resistance to prior imatinib therapy, primarily in advanced phase disease.
Embryo-Fetal Toxicity Based on limited human data, SPRYCEL can cause fetal harm when administered to a pregnant woman. Hydrops fetalis, fetal leukopenia and fetal thrombocytopenia have been reported with maternal exposure to SPRYCEL. Transplacental transfer of dasatinib has been measured in fetal plasma and amniotic fluid at concentrations comparable to those in maternal plasma.
Lactation No data are available regarding the presence of dasatinib in human milk, the effects of the drug on the breastfed infant or the effects of the drug on milk production. However, dasatinib is present in the milk of lactating rats.
Drug Interactions (News - Alert) SPRYCEL is a CYP3A4 substrate and a weak time-dependent inhibitor of CYP3A4.
Adverse Reactions The safety data reflects exposure to SPRYCEL at all doses tested in clinical studies including 324 patients with newly diagnosed chronic phase CML and 2388 patients with imatinib resistant or intolerant chronic or advanced phase CML or Ph+ ALL. The median duration of therapy in all 2712 SPRYCEL-treated patients was 19.2 months (range 0-93.2 months). Median duration of therapy in:
In the newly diagnosed chronic phase CML trial, after a minimum of 60 months of follow-up, the cumulative discontinuation rate for 258 patients was 39%. In the overall population of 2712 SPRYCEL-treated patients, 88% of patients experienced adverse reactions at some time and 19% experienced adverse reactions leading to treatment discontinuation. Among the 1618 SPRYCEL-treated patients with chronic phase CML, drug-related adverse events leading to discontinuation were reported in 329 (20.3%) patients.
Among the 1094 SPRYCEL-treated patients with advanced phase CML or Ph+ ALL, drug-related adverse events leading to discontinuation were reported in 191 (17.5%) patients. Patients =65 years are more likely to experience the commonly reported adverse reactions of fatigue, pleural effusion, diarrhea, dyspnea, cough, lower gastrointestinal hemorrhage, and appetite disturbance, and more likely to experience the less frequently reported adverse reactions of abdominal distention, dizziness, pericardial effusion, congestive heart failure, hypertension, pulmonary edema and weight decrease, and should be monitored closely.
Please see the full Prescribing Information for SPRYCEL. Please see the US full Prescribing Information here. About Bristol-Myers Squibb Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook. Bristol-Myers Squibb Forward-Looking Statement This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of 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 Sprycel will receive regulatory approval for an additional indication described herein. Forward-looking statements in this 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, 2016 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.
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