Learn more about RYDAPT® (midostaurin) capsules at www.HCP-RYDAPT.com       View this as a Web page             Prescribing Information Important Safety Information         Changing the treatment landscape of AML* for 1000 patients and more1,2         * For the treatment of adult patients with newly diagnosed FLT3+ acute myeloid leukemia (AML)           ...AND STILL MORE TO COME     RATIFY RESULTS: SIGNIFICANT AND SUSTAINED SURVIVAL BENEFITS WITH RYDAPT1           IN THE RISK OF DEATH COMPARED WITH STANDARD CHEMOTHERAPY PLUS PLACEBO: HR=0.77 (95% CI, 0.629-0.953), P=.016         • Because survival curves plateaued before reaching the median, median survival could not be reliably estimated   • The primary end point in RATIFY was overall survival (OS). Efficacy was established on the basis of OS, measured from the date of randomization until death by any cause       RATIFY: A phase 3, randomized, double-blind, placebo-controlled, international study of 717 patients with newly diagnosed FLT3+ AML that compared RYDAPT plus standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy (n=360) vs standard chemotherapy plus placebo (n=357), followed by continuous RYDAPT or placebo treatment according to initial assignment for up to 12 additional 28-day cycles. Standard chemotherapy is induction therapy with cytarabine 200 mg/m2/day on Days 1-7 and daunorubicin 60 mg/m2/day on Days 1-3 and consolidation therapy with high-dose cytarabine 3 g/m2 every 12 hours on Days 1, 3, and 5. Patients were given RYDAPT 50 mg twice daily with food on Days 8-21 in the induction and consolidation therapy cycles and on Days 1-28 during postconsolidation therapy. There was no re-randomization at the start of postconsolidation therapy and, therefore, there is no assessment of the efficacy of RYDAPT in this stage alone. Patients who proceeded to hematopoietic stem cell transplantation stopped receiving study treatment. All patients were followed for survival.1,3       GREATER EFS WITH RYDAPT PLUS STANDARD CHEMOTHERAPY VS STANDARD CHEMOTHERAPY PLUS PLACEBO1       • Median duration of complete remission (CR) within 60 days of treatment start: 8.2 vs 3.0 months, respectively; HR=0.78 (95% CI, 0.66-0.93; P=.005)   –   Event-free survival (EFS) was defined as a failure to obtain a CR within 60 days of initiation of protocol therapy, relapse, or death from any cause   • Median duration of CR anytime during induction: 10.6 vs 5.6 months, respectively; HR=0.72 (95% CI, 0.61-0.86)   –   An exploratory analysis of EFS, defined as a failure to obtain a CR anytime during induction, relapse, or death from any cause, with failures assigned as an event on study Day 1   • The most frequent (≥20%) adverse drug reactions in the RYDAPT plus chemotherapy arm were febrile neutropenia, nausea, mucositis, vomiting, headache, petechiae, musculoskeletal pain, epistaxis, device-related infection, hyperglycemia, and upper respiratory tract infections. The most frequent grade 3/4 adverse reactions (≥10%) were febrile neutropenia, device-related infection, and mucositis       LEARN MORE ABOUT RYDAPT     IN NEWLY DIAGNOSED FLT3+ AML       INDICATION RYDAPT is indicated, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive, as detected by an FDA-approved test.       LIMITATIONS OF USE RYDAPT is not indicated as a single-agent induction therapy for the treatment of patients with AML.       IMPORTANT SAFETY INFORMATION for RYDAPT® (midostaurin) capsules CONTRAINDICATIONS     • Do not use in patients with hypersensitivity to midostaurin or its excipients. Hypersensitivity reactions have included anaphylactic shock, dyspnea, flushing, chest pain, and angioedema       WARNINGS AND PRECAUTIONS Embryofetal Toxicity     • Do not use during pregnancy. Midostaurin caused severe embryofetal abnormalities and death in animal studies     • Verify pregnancy status of females of reproductive potential within 7 days prior to initiating RYDAPT     • Advise females of reproductive potential to use effective contraception during treatment and for at least 4 months after the last dose     • Males taking RYDAPT should use effective contraception with females of reproductive potential and pregnant women and for at least 4 months after the last dose     • Pregnancy exposure registry to monitor pregnancy outcomes: Females who may have been exposed to RYDAPT during pregnancy, directly or through a male partner receiving RYDAPT, should contact Novartis Pharmaceuticals Corporation at 1-8‍88-6‍69-66‍82 and/or at ht‍tps://p‍si.nov‍artis.c‍om       Pulmonary Toxicity     • Cases of interstitial lung disease and pneumonitis, some fatal, have occurred in patients treated with RYDAPT as monotherapy or with chemotherapy     • Monitor patients for pulmonary symptoms. Discontinue RYDAPT in patients who experience signs or symptoms of interstitial lung disease or pneumonitis without an infectious etiology       ADDITIONAL CONSIDERATIONS Lactation     • Because of the potential for serious adverse reactions in breastfed infants from RYDAPT, advise women not to breastfeed during treatment with RYDAPT and for at least 4 months after the last dose       Infertility     • Based on findings in animals, RYDAPT may impair fertility in females and males of reproductive potential. It is unknown whether these effects on fertility are reversible       Drug Interactions     • Strong CYP3A4 Inducers: Avoid concomitant use as strong CYP3A4 inducers decrease exposure to midostaurin and may reduce efficacy     • Strong CYP3A4 Inhibitors: Coadministration with strong CYP3A4 inhibitors may increase midostaurin concentrations and may increase the risk of toxicity. Monitor patients for increased risk of adverse reactions, especially during the first week of RYDAPT use in each chemotherapy cycle and the first week of consecutive RYDAPT administration. Consider alternative therapies that do not strongly inhibit CYP3A4 activity       ADVERSE REACTIONS Acute Myeloid Leukemia     • Most common adverse reactions (≥20%) were febrile neutropenia (83%), nausea (83%), mucositis (66%), vomiting (61%), headache (46%), petechiae (36%), musculoskeletal pain (33%), epistaxis (28%), device-related infection (24%), hyperglycemia (20%), and upper respiratory tract infection (20%)     • Most frequent grade 3/4 adverse reactions (≥10%) were febrile neutropenia (84%), device-related infection (16%), and mucositis (11%)     • Most common (≥10%) lab abnormalities were alanine aminotransferase increase (71%), hypernatremia (21%), and hypocalcemia (74%)       Please see full Prescribing Information for RYDAPT® (midostaurin) capsules.       FLT3, FMS-like tyrosine kinase 3.       References: 1. Rydapt [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2018. 2. Data on file. US Rydapt AML FLT3 Testing and Rydapt AML Patients. Novartis Pharmaceuticals Corp; 2018. 3. Data on file. Study no. CPKC412A2301. Novartis Pharmaceuticals Corp; 2016.       This is a sponsored message from DMD on behalf of Novartis Pharmaceuticals Corporation. DMD provides sponsored health care–related messages from trusted third parties. This material is intended specifically and exclusively for US health care professionals. You are receiving this email because you have subscribed and agreed to receive information from the DMD email list.       If you prefer not to receive further messages from DMD, please click here and confirm your request.       DMD 10‍255 W. Hig‍gins Ro‍ad, Su‍ite 280 Rose‍mont, I‍L 60‍018       DMD Privacy Policy               Novartis Pharmaceuticals Corporation         © 20‍18 Novartis 10/1‍8 MID-1188482