Torsades De Pointes

10,000-square-foot facility to house corporate offices and serve as a center for meetings and events with members of the Duchenne muscular dystrophy and other rare disease communities CONCORD, Mass., March 5, 2025 /PRNewswire/ -- ITF Therapeutics LLC, the U.S. affiliate of Italfarmaco, today announced the opening of the company's new U.S. headquarters in Concord, Massachusetts. The 10,000-square-foot facility located at 575 Virginia Road, Unit 201, will include corporate offices as well as meeting spaces where ITF will welcome members of the Duchenne muscular dystrophy (DMD) and other rare disease communities. "ITF Therapeutics was founded only one year ago, and in that short time we have rapidly expanded our team to include specialists who are working to make a positive difference for people living with rare diseases and we announced the FDA approval and commercial launch of our first product, DUVYZAT™ (givinostat)," said Matt Trudeau, president, ITF Therapeutics. "Our new U.S. headquarters in Concord will help us continue the momentum, bringing together more of our team members to plan for many exciting new opportunities for our company. The office will also be a welcoming space where members of the communities we serve can share their insights with us to keep their voices front and center in our work." The headquarters will accommodate up to 40 members of the ITF Therapeutics team. In planning the design of the headquarters, ITF worked closely with leaders from the patient advocacy community to understand and incorporate features that support accessibility and comfort for guests. "As we planned for our new office, members of our team at every level stressed the importance of making this a space that reflects our focus on honoring the experiences of people living with DMD and their families," Trudeau added. "We are very much looking forward to hosting community members and creating many new opportunities for them to engage with ITF Therapeutics in meaningful ways." Please see the Indication and Important Safety Information for DUVYZAT below. About DUVYZAT™ (givinostat) DUVYZAT is a U.S. FDA-approved histone deacetylase (HDAC) inhibitor indicated for the treatment of patients six years of age and older with Duchenne muscular dystrophy (DMD) that was discovered through the research and development efforts of Italfarmaco in collaboration with Telethon and Duchenne Parent Project (Italy). HDACs are enzymes located in the body's cells that play a key role in maintaining and repairing muscles. In DMD, the HDAC enzymes become overactive, leading to chronic muscle inflammation, decreased muscle repair, and replacement of muscle with fat and scar tissue. DUVYZAT inhibits HDAC overactivity and is thought to help reduce inflammation, increase the body's ability to repair muscles, and slow muscle loss. For more information visit . About ITF Therapeutics LLC ITF Therapeutics was launched in January 2024 as the U.S. affiliate of Italfarmaco focused on the development and commercialization of products to treat rare diseases. Building on a legacy grounded in collaboration and innovation, ITF Therapeutics strives to partner with leaders from the patient advocacy and treatment communities to ensure that our programs reflect and support their unique needs and goals. The establishment of ITF Therapeutics reflects Italfarmaco's goal to build a world-class team of experts who share a passion to make a positive impact for rare disease communities. For more information visit . About Italfarmaco Founded in 1938 in Milan, Italy, Italfarmaco is a private global pharmaceutical company that has led the successful development and approval of many pharmaceutical products around the world. The Italfarmaco group has operations in more than 90 countries through directly controlled or affiliated companies. The company is a leader in pharmaceutical research, product development, production, and commercialization with proven success in many therapeutic areas including immuno-oncology, gynecology, neurology, cardiovascular disease, and rare diseases. Italfarmaco's rare disease unit includes programs in Duchenne muscular dystrophy, Becker muscular dystrophy, amyotrophic lateral sclerosis, and polycythemia vera. For more information visit . Indication and Important Safety Information What is DUVYZAT? DUVYZAT is a prescription medicine that is used for the treatment of Duchenne muscular dystrophy (DMD) in people 6 years of age and older. It is not known if DUVYZAT is safe and effective in children under 6 years of age. Important Safety Information What is the most important information I should know about DUVYZAT? Low platelet counts in your blood (thrombocytopenia). Platelets are important for blood clotting, and a decrease in their numbers can lead to an increased risk of bleeding or bruising. Your healthcare provider will check your blood count before you start DUVYZAT and regularly during treatment for any signs of thrombocytopenia. Call your healthcare provider right away if you notice any unusual bleeding or small red or purple spots on the skin called petechiae. Your healthcare provider may change your dose of DUVYZAT if your blood platelet counts continue to be low or may stop your treatment with DUVYZAT. Increased levels of fat (triglycerides) in your blood. You may not have any symptoms, so your healthcare provider will do blood tests before you start DUVYZAT and regularly during treatment to check your triglyceride levels. Your healthcare provider may change your dose of DUVYZAT if your triglyceride levels continue to be high or may stop your treatment with DUVYZAT. Frequent watery loose stools (diarrhea) and vomiting. DUVYZAT can cause vomiting and moderate to severe diarrhea. If diarrhea occurs, you should keep track of the frequency and severity of your diarrhea symptoms, drink plenty of fluids, and contact your healthcare provider. Your healthcare provider may change your dose of DUVYZAT if the diarrhea cannot be managed or does not go away. Your healthcare provider may also stop your treatment with DUVYZAT. Before taking DUVYZAT, tell your healthcare provider about all of your medical conditions, including if you: have any heart problems or if you take any medicines that could increase your chance for irregular heart rhythms. have any bleeding problems. Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking DUVYZAT with certain other medicines may affect each other. Taking DUVYZAT with other medicines can cause serious side effects. Do not start or stop other medicines without talking to your healthcare provider. DUVYZAT can cause serious side effects, including: See "What is the most important information I should know about DUVYZAT?" Changes in the electrical activity of your heart called QT Prolongation. QT Prolongation can increase the risk of developing a type of irregular heart rhythm known as Torsades de Pointes. Call your healthcare provider right away if you feel faint, have an irregular heartbeat, feel dizzy, or lose consciousness. The most common side effects of DUVYZAT included diarrhea, nausea, vomiting, stomach pain, low platelet counts in the blood, increased fat level in the blood, and fever. These are not all of the possible side effects of DUVYZAT. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Please see full Prescribing Information and Medication Guide. DUVYZAT is a registered trademark of Italfarmaco S.p.A. U.S.A. Media inquiries: Brian Connor | +1 212 253 8881 | [email protected] Other inquiries: Patient Advocacy and Communications Lead U.S.A. | [email protected] Global Media inquiries: Charlotte Spitz or Jacob Verghese | +49 (0)151 7441 6179 | [email protected] Other inquiries: Patient Advocacy and Communications Lead | [email protected] C-DUV-US-0318 02/2025 SOURCE ITF Therapeutics LLC WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

CHICAGO--( BUSINESS WIRE )--Meitheal Pharmaceuticals, Inc. (“Meitheal”), a fully integrated biopharmaceutical company based in Chicago focused on the development and commercialization of generic, fertility, biologic, and branded injectable products, announced it has secured exclusive commercial rights in the U.S. to XENLETA ® (lefamulin acetate) through an exclusive license and supply agreement with its parent company, Hong Kong King-Friend Industrial Co., Ltd. (HKF). XENLETA ® belongs to a new class of novel antibiotics and is approved in intravenous and oral formulations in the U.S. and multiple other countries for the treatment of community-acquired bacterial pneumonia (CABP) in adults. HKF has acquired global rights to XENLETA ® (with the exception of Greater China) from Nabriva Therapeutics. Through the acquisition, HKF has obtained substantially all global assets related to XENLETA ® , including results of development and regulatory activities. “The licensing of XENLETA ® bolsters our portfolio of novel antibiotics and reflects our focus on addressing the growing issue of antimicrobial resistance,” said Tom Shea, Chief Executive Officer of Meitheal. “As the first approved medicine of an entirely new class of antibiotics, XENLETA ® is an innovative therapeutic option that will be available to the patients affected by CABP and has been shown to be active against various bacterial strains. We look forward to leveraging our end-to-end expertise in biopharmaceutical development and commercialization to bring this important therapeutic to patients in need.” XENLETA ® is a first-in-class semi-synthetic pleuromutilin antibiotic. As a monotherapy offering a complete spectrum of coverage for the main CABP pathogens and with a low propensity for the development of bacterial resistance, XENLETA ® represents a critical step in addressing the growing global public health crisis of antimicrobial resistance (AMR) and supports the principles of antimicrobial stewardship. “Antimicrobial resistance, unfortunately, undermines the treatment paradigms of many infectious diseases globally, leading to poor patient outcomes and increased costs to healthcare systems,” said Brett Novak, Meitheal’s Senior Vice President of Commercial Operations. “XENLETA ® provides a unique and well-tolerated product profile for the more than five million annual cases of CABP in the U.S., where it has the potential to serve as a first-line monotherapy option in both the inpatient and outpatient settings. We are pleased that this agreement will allow us to unlock synergies with our existing franchises and deliver critical medicines that address large gaps in the antibiotic treatment landscape.” Global approvals of XENLETA ® in CABP are based on the results of two global, pivotal Phase 3 trials, LEAP 1 and LEAP 2, in which XENLETA ® met all primary endpoints. Meitheal recently added the first anti-infective to its portfolio through an exclusive commercialization agreement with HKF—CONTEPO™. Meitheal will leverage its new aligned-to-CONTEPO ™ marketing, sales, and medical science liaison teams to support the launch of XENLETA ® , which shares similar hospital call points. Meitheal will further establish practice-based support for key prescribers and patients that could benefit from XENLETA ® . “We are pleased to have acquired the rights to XENLETA ® and look forward to supporting Meitheal as it delivers this important medication to patients in the U.S.,” said Eric Tang, President of HKF. “We are committed to supporting Meitheal’s work to deliver accessible, sustainable, and innovative healthcare solutions and we remain focused on continuing to invest in the research, development, and commercialization of branded pharmaceuticals to achieve this goal.” HKF and its related entities have invested over $300 million in capital and research and development in recent years to support sustainable product supply across key focus areas, including branded biopharmaceuticals. The licensing agreement for XENLETA ® adds a third branded biopharmaceutical and first on-market branded product to Meitheal’s portfolio. ABOUT COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA (CABP) Pneumonia is an infection of the lung that can be serious and fatal, especially among older adult patients with comorbidities. CABP is among the most common types of pneumonia, with five million cases in the U.S. each year. 1 In the U.S., CABP is the leading cause of infection-related death 2 and the fourth leading cause of hospitalization, 3 a setting where mortality rates are approximately 15% 4 . Certain bacteria that cause CABP have become resistant to one common antibiotic, macrolides, at a rate on average of 50%. 5 The U.S. FDA has also issued multiple warnings about the resistance of one current class of CABP treatments called fluoroquinolones. 6 Antimicrobial resistance (AMR) is a top global public health threat that creates challenges treating infections and performing medical procedures and increases the risk of death and disability. 7 Novel antibiotics that kill bacteria, including those that cause CABP, in a different way are essential to addressing AMR. 8 ABOUT XENLETA ® XENLETA ® (lefamulin acetate) is a first-in-class, semi-synthetic pleuromutilin antibiotic for systemic administration in humans. It is designed to inhibit the synthesis of bacterial protein, which is required for bacteria to grow. XENLETA ® ’s binding occurs with high affinity, high specificity, and at molecular sites that are different than other antibiotic classes. Two multicenter, multinational, double-blind, double-dummy, non-inferiority trials assessing a total of 1,289 patients with CABP demonstrated XENLETA ® ’s efficacy. In these trials, XENLETA ® was compared with moxifloxacin, and in one trial, moxifloxacin with and without linezolid. Patients who received XENLETA ® had similar rates of efficacy as those taking moxifloxacin alone or moxifloxacin plus linezolid. CONTRAINDICATIONS XENLETA ® is contraindicated in patients with known hypersensitivity to lefamulin, pleuromutilin class drugs, or any of the components of XENLETA ® . Concomitant use of XENLETA ® tablets with CYP3A substrates that prolong the QT interval is contraindicated. WARNINGS AND PRECAUTIONS QT Prolongation: Avoid use in patients with known QT prolongation, ventricular arrhythmias including torsades de pointes, and patients receiving drugs that prolong the QT interval such as antiarrhythmic agents. Embryo-Fetal Toxicity: May cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception. Clostridioides difficile-associated Diarrhea: Evaluate patients who develop diarrhea. ADVERSE REACTIONS The most common adverse reactions associated with XENLETA ® Injection include administration site reactions, hepatic enzyme elevation, nausea, hypokalemia, insomnia and headache. The most common adverse reactions associated with XENLETA ® Tablets include diarrhea, nausea, vomiting, hepatic enzyme elevation. Please see Full Prescribing Information for more information. ABOUT MEITHEAL PHARMACEUTICALS, INC. Founded in 2017 and based in Chicago, Meitheal is focused on the development and commercialization of generic injectable medications and, as of 2022, has expanded its focus to include fertility, biologic, and branded products. Meitheal currently markets over 60 U.S. Food and Drug Administration (FDA)-approved products across numerous therapeutic areas including anti-infectives, oncolytics, intensive care, and fertility. As of October 2024, Meitheal, directly or through its partners, has 18 products in the research and development phase, 6 additional products planned for launch in 2024, and 21 products under review by the FDA. Meitheal’s mission is to provide easy access to fairly-priced products through robust manufacturing, consistent supply, and rapid response to our customers’ needs. Ranked #2 in 2024 on Crain’s Fast 50 in Chicago, and in the top 100 of Crain’s Best Places to Work in Chicago from 2022 to 2024, Meitheal emulates the traditional Irish guiding principle we are named for — working together toward a common goal, for the greater good. Learn more about who we are and what we do at www.meithealpharma.com . ABOUT HONG KONG KING-FRIEND INDUSTRIAL COMPANY (HKF) Hong Kong King-Friend Industrial Company is a wholly owned subsidiary of Nanjing King-Friend Biochemical Pharmaceutical Company, founded in 2010. ABOUT NANJING KING-FRIEND BIOCHEMICAL PHARMACEUTICAL COMPANY (NKF) Nanjing King-Friend Biochemical Pharmaceutical Co., Ltd. is a China-based company principally engaged in the research and development, production and sales of Active Pharmaceutical Ingredients (API) and Finished Dosage Form (FDF). Established in 1986 as one of the world’s leading manufacturers of heparin-related APIs, NKF has grown into a fully integrated API and FDF manufacturer in multiple therapeutic areas including critical care and oncology. With three U.S. FDA-approved manufacturing sites in China and more than 500 employees, including more than 100 dedicated research and development experts, NKF strives to meet patient needs globally with market presence in the U.S., China, EU and across the world. NKF is publicly listed on the Shanghai Stock Exchange with a market capitalization over U.S. $3.0 billion. ABOUT NABRIVA THERAPEUTICS PLC Nabriva Therapeutics is a biopharmaceutical company engaged in the commercialization and development of innovative anti-infective agents to treat serious infections. Nabriva Therapeutics received U.S. FDA approval for XENLETA ® (lefamulin injection, lefamulin tablets), the first systemic pleuromutilin antibiotic for community-acquired bacterial pneumonia (CABP). Nabriva Therapeutics also previously developed CONTEPO™ (fosfomycin for injection), a potential first-in-class epoxide antibiotic for complicated urinary tract infections (cUTI). ___________________________ 1 National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) 2009 -2010. https://archive.cdc.gov/#/details?url=https://www.cdc.gov/nchs/data/ahcd/combined_tables/2009-2010_combined_web_table01.pdf (Last Accessed December 4, 2024). 2 el Bcheraoui C, Mokdad AH, Dwyer-Lindgren L, et al. Trends and Patterns of Differences in Infectious Disease Mortality Among US Counties, 1980-2014. JAMA.2018;319(12):1248–1260. doi:10.1001/jama.2018.2089. 3 McDermott KW, Roemer M. Most frequent principal diagnoses for inpatient stays in U.S. Hospitals, 2018: Statistical Brief, no 277. In: Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. Rockville, MD: Agency for Healthcare Research and Quality. 2021. https://hcup-us.ahrq.gov/reports/statbriefs/sb277-Top-Reasons-Hospital-Stays-2018.pdf . 4 2017 CHARTBOOK STATIC ANALYSES -Trends in mortality rates following admission for acute myocardial infarction, chronic obstructive pulmonary disease, heart failure, pneumonia, and acute ischemic stroke. Prepared for CMS by Yale New Haven Health Services Corporation -Center for Outcomes Research and Evaluation (YNHHSC/CORE) September 2017. 5 Classi P, Landsman-Blumberg P, Carroll C, et al. The relationship between macrolide-resistant streptococcus pneumoniae and treatment failure in adults with community-acquired pneumonia by CDC region in the United States. Abstract J03. In: Meeting abstracts, Academy of Managed Care Pharmacy Nexus 2016; October 3-6, 2016; National Harbor, MD. 6 Food and Drug Administration. FDA updates warnings for fluoroquinolone antibiotics on risks of mental health and low blood sugar adverse reactions. https://www.fda.gov/news-events/press-announcements/fda-updates-warnings-fluoroquinolone-antibiotics-risks-mental-health-and-low-blood-sugar-adverse . Accessed December 4, 2024. 7 World Health Organization. Antimicrobial resistance. https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance . Accessed December 4, 2024. 8 Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013, US Department of Health and Human Services.

TOKYO & BASKING RIDGE, N.J.--( BUSINESS WIRE )--The first patient has been dosed in the QuANTUM-Wild phase 3 trial evaluating Daiichi Sankyo’s (TSE: 4568) VANFLYTA ® (quizartinib) in combination with standard intensive induction and consolidation chemotherapy followed by single-agent maintenance in adults with newly diagnosed FLT3 -ITD negative acute myeloid leukemia (AML). AML is an aggressive blood cancer with a five-year overall survival rate of approximately 32%. 1, 2 Targeted therapy with FLT3 inhibitors has improved survival for some patients with FLT3 gene mutations, which most commonly occur as FLT3 -ITD. 3 However, about 90% of patients with AML overexpress FLT3 regardless of mutational status. 1, 4, 5 No FLT3 inhibitors are currently approved for patients without FLT3 mutations. “Preliminary data have shown promising results for VANFLYTA in patients with FLT3 -ITD negative acute myeloid leukemia, which includes patients without FLT3 mutations and patients with TKD mutations,” said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. “We have initiated the QuANTUM-Wild trial to further confirm the potential role of VANFLYTA combined with standard chemotherapy and as subsequent maintenance monotherapy in this broader population of patients with AML who are in need of new treatment options to potentially reduce the risk of relapse and improve overall survival.” The QuANTUM-Wild trial was initiated based on results of the QUIWI phase 2 trial evaluating VANFLYTA in combination with standard intensive chemotherapy and as subsequent maintenance monotherapy in adult patients with newly diagnosed FLT3 -ITD negative AML. The final results of QUIWI were presented at the 2024 American Society of Hematology Annual Meeting. 6 About the QuANTUM-Wild Trial QuANTUM-Wild is a randomized, double-blind, placebo-controlled global phase 3 trial evaluating the efficacy and safety of VANFLYTA in combination with standard intensive induction and consolidation therapy, including allogenic hematopoietic stem cell transplant (HSCT), followed by maintenance monotherapy, in adult patients aged 18 to 70 with newly diagnosed FLT3 -ITD negative AML. Patients will be randomized 2:2:1 into three treatment arms. In Arms A and B, patients will receive VANFLYTA or placebo, respectively, in combination with cytarabine and anthracycline induction and cytarabine consolidation chemotherapy, followed by up to three years of single-agent maintenance therapy. The primary endpoint for Arms A and B is overall survival. Secondary endpoints include event-free survival, duration of complete response, relapse-free survival, complete remission rate (CR), CR with minimal or measurable residual disease negativity, pharmacokinetic assessments and safety measures including treatment emergent adverse events. For purposes of exploratory analyses in the maintenance setting, patients in a third study arm (Arm C), will receive VANFLYTA in combination with intensive induction and consolidation chemotherapy followed by placebo maintenance monotherapy. QuANTUM-Wild is expected to enroll approximately 700 patients across Asia, Australia, Europe, North America and South America. For more information, please visit ClinicalTrials.gov . About Acute Myeloid Leukemia One of the most common forms of leukemia in adults, AML is an aggressive blood cancer with a five-year overall survival rate of approximately 32%. 1, 2, 3 Approximately 144,000 new cases of AML were diagnosed globally with more than 130,000 deaths reported in 2021. 7 Targeted therapy with FLT3 inhibitors has improved survival for some patients with FLT3 gene mutations, which most commonly occur as FLT3 -ITD. 3 However, about 90% of all patients with AML overexpress FLT3 regardless of activating mutations. 1, 4, 5 No FLT3 inhibitors are currently approved for patients without FLT3 mutations. FLT3 is a receptor tyrosine kinase protein that plays an important role in blood cell development but, when constitutively activated, FLT3 can contribute to AML development and growth. 8 About VANFLYTA VANFLYTA is an oral, highly potent and selective type II FLT3 inhibitor approved in more than 30 countries in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, and as maintenance monotherapy following consolidation, for the treatment of adult patients with newly diagnosed AML that is FLT3 -ITD positive based on the results from the QuANTUM-First trial. In the U.S., VANFLYTA is not indicated as maintenance monotherapy following allogeneic HSCT; improvement in overall survival with VANFLYTA in this setting has not been demonstrated. VANFLYTA also is approved in Japan for the treatment of patients with relapsed/refractory AML that is FLT3 -ITD mutation positive, as detected by an approved test, based on results from the QuANTUM-R trial. About the VANFLYTA Clinical Development Program The VANFLYTA clinical development program includes the QuANTUM-Wild phase 3 trial in adult patients with newly diagnosed FLT3 -ITD negative AML, a phase 1/2 trial in pediatric and young adult patients with relapsed/refractory FLT3 -ITD positive AML in Europe, Asia and North America and several phase 1/2 combination studies as part of a strategic collaboration with The University of Texas MD Anderson Cancer Center. VANFLYTA U.S. Important Safety Information WARNING: QT PROLONGATION, TORSADES DE POINTES, and CARDIAC ARREST VANFLYTA ® (quizartinib) prolongs the QT interval in a dose- and concentration-related manner. Prior to VANFLYTA administration and periodically, monitor for hypokalemia or hypomagnesemia, and correct deficiencies. Perform electrocardiograms (ECGs) to monitor the QTc at baseline, weekly during induction and consolidation therapy, weekly for at least the first month of maintenance, and periodically thereafter. Torsades de pointes and cardiac arrest have occurred in patients receiving VANFLYTA. Do not administer VANFLYTA to patients with severe hypokalemia, severe hypomagnesemia, or long QT syndrome. Do not initiate treatment with VANFLYTA or escalate the VANFLYTA dose if the QT interval corrected by Fridericia’s formula (QTcF) is greater than 450 ms. Monitor ECGs more frequently if concomitant use of drugs known to prolong the QT interval is required. Reduce the VANFLYTA dose when used concomitantly with strong CYP3A inhibitors, as they may increase quizartinib exposure. Because of the risk of QT prolongation, VANFLYTA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the VANFLYTA REMS. Indication VANFLYTA is indicated in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)–positive as detected by an FDA-approved test. Limitations of Use VANFLYTA is not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation (HSCT); improvement in overall survival with VANFLYTA in this setting has not been demonstrated. Contraindications VANFLYTA is contraindicated in patients with severe hypokalemia, severe hypomagnesemia, long QT syndrome, or in patients with a history of ventricular arrhythmias or torsades de pointes. Warnings and Precautions QT Prolongation, Torsades de Pointes, and Cardiac Arrest (See BOXED WARNING) VANFLYTA prolongs the QT interval in a dose- and concentration-dependent manner. The mechanism of QTc interval prolongation is via inhibition of the slow delayed rectifier potassium current, I Ks , as compared to all other medications that prolong the QTc interval, which is via the rapid delayed rectifier potassium current, I Kr . Therefore, the level of QTc prolongation with VANFLYTA that predicts the risk of cardiac arrhythmias is unclear. Inhibition of I Ks and I Kr may leave patients with limited reserve, leading to a higher risk of QT prolongation and serious cardiac arrhythmias, including fatal outcomes. Torsades de pointes, ventricular fibrillation, cardiac arrest, and sudden death have occurred in patients treated with VANFLYTA. Of the 1,081 patients with AML treated with VANFLYTA in clinical trials, torsades de pointes occurred in approximately 0.2% of patients, cardiac arrest occurred in 0.6% of patients, including 0.4% with a fatal outcome, and 0.1% of patients experienced ventricular fibrillation. These severe cardiac arrhythmias occurred predominantly during the induction phase. Of the 265 patients with newly diagnosed FLT3-ITD–positive AML treated with VANFLYTA in combination with chemotherapy in the clinical trial, 2.3% were found to have a QTcF greater than 500 ms and 10% of patients had an increase from baseline QTcF greater than 60 ms. The clinical trial excluded patients with a QTcF ≥450 ms or other factors that increased the risk of QT prolongation or arrhythmic events (eg, NYHA Class III or IV congestive heart failure, hypokalemia, family history of long QT interval syndrome). Therefore, avoid use in patients who are at significant risk of developing torsades de pointes, including uncontrolled or significant cardiac disease, recent myocardial infarction, heart failure, unstable angina, bradyarrhythmias, tachyarrhythmias, uncontrolled hypertension, high-degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism. Do not initiate treatment with VANFLYTA if the QTcF interval is greater than 450 ms. Do not use VANFLYTA in patients with severe hypokalemia, severe hypomagnesemia, long QT syndrome, or in patients with a history of ventricular arrhythmias or torsades de pointes. Perform an ECG and correct electrolyte abnormalities prior to initiation of treatment with VANFLYTA. During induction and consolidation, perform an ECG prior to initiation and then once weekly during VANFLYTA treatment or more frequently as clinically indicated. During maintenance, perform ECGs prior to initiation, once weekly for at least the first month following dose initiation and escalation, and as clinically indicated thereafter. Do not escalate the dose if QTcF is greater than 450 ms. Perform ECG monitoring of the QT interval more frequently in patients who are at significant risk of developing QT interval prolongation and torsades de pointes, or following dose escalation. Monitor and correct hypokalemia and hypomagnesemia prior to and during treatment with VANFLYTA. Maintain electrolytes in the normal range. Monitor electrolytes and ECGs more frequently in patients who experience diarrhea or vomiting. Monitor patients more frequently with ECGs if coadministration of VANFLYTA with drugs known to prolong the QT interval is required. Reduce the VANFLYTA dose when used concomitantly with strong CYP3A inhibitors, as they may increase quizartinib exposure. Reduce VANFLYTA if QTc increases to greater than 480 ms and less than 500 ms. Interrupt and reduce VANFLYTA if QTc increases to greater than 500 ms. Permanently discontinue VANFLYTA in patients who develop recurrent QTc greater than 500 ms or QTc interval prolongation with signs or symptoms of life-threatening arrhythmia. VANFLYTA is available only through a restricted program under a REMS. VANFLYTA REMS VANFLYTA is available only through a restricted distribution program under a REMS called the VANFLYTA REMS because of the serious risk of QT prolongation, torsades de pointes, and cardiac arrest. Notable requirements of the VANFLYTA REMS include the following: Prescribers must be certified in the VANFLYTA REMS by enrolling and completing training. Prescribers must counsel patients receiving VANFLYTA about the risk of QT prolongation, torsades de pointes, and cardiac arrest, and provide patients with a Patient Wallet Card. Pharmacies that dispense VANFLYTA must be certified with the VANFLYTA REMS and must verify prescribers are certified through the VANFLYTA REMS. Further information about the VANFLYTA REMS is available at www.VANFLYTAREMS.com or by telephone at 1-855-212-6670. Embryo-Fetal Toxicity Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with VANFLYTA and for 7 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with VANFLYTA and for 4 months after the last dose. Adverse Reactions The safety of VANFLYTA (35.4 mg orally once daily with chemotherapy, 26.5 mg to 53 mg orally once daily as maintenance) in adult patients with newly diagnosed FLT3-ITD positive AML is based on QuANTUM-First. Serious adverse reactions in ≥5% of patients who received VANFLYTA plus chemotherapy were: febrile neutropenia (11%). Fatal adverse reactions occurred in 10% of patients who received VANFLYTA plus chemotherapy, including sepsis (5%), fungal infections (0.8%), brain edema (0.8%), and one case each of febrile neutropenia, pneumonia, cerebral infarction, acute respiratory distress syndrome, pulmonary embolism, ventricular dysfunction, and cardiac arrest. Permanent discontinuation due to an adverse reaction in patients in the VANFLYTA plus chemotherapy arm occurred in 20% of patients. The most frequent (≥2%) adverse reaction which resulted in permanent discontinuation in the VANFLYTA arm was sepsis (5%). Dosage interruptions of VANFLYTA due to an adverse reaction occurred in 34% of patients. Adverse reactions which required dosage interruption in ≥2% of patients in the VANFLYTA arm included neutropenia (11%), thrombocytopenia (5%), and myelosuppression (3%). Dose reductions of VANFLYTA due to an adverse reaction occurred in 19% of patients. Adverse reactions which required dosage reductions in ≥2% of patients in the VANFLYTA arm were neutropenia (9%), thrombocytopenia (5%), and electrocardiogram QT prolonged (4%). The most common adverse reactions (≥10% with a difference between arms of ≥2% compared to placebo), including laboratory abnormalities, were decreased lymphocytes, decreased potassium, decreased albumin, decreased phosphorus, increased alkaline phosphatase, decreased magnesium, febrile neutropenia, diarrhea, mucositis, nausea, decreased calcium, abdominal pain, sepsis, neutropenia, headache, increased creatine phosphokinase, vomiting, upper respiratory tract infections, hypertransaminasemia, thrombocytopenia, decreased appetite, fungal infections, epistaxis, increased potassium, herpesvirus infections, insomnia, QT prolongation, increased magnesium, increased sodium, dyspepsia, anemia, and eye irritation. Drug Interactions Strong CYP3A Inhibitors VANFLYTA is a CYP3A substrate. Concomitant use of VANFLYTA with a strong CYP3A inhibitor increases quizartinib systemic exposure, which may increase the risk of VANFLYTA adverse reactions. Reduce the dosage of VANFLYTA. Strong or Moderate CYP3A Inducers Concomitant use of VANFLYTA with strong or moderate CYP3A inducers decreases quizartinib systemic exposure, which may reduce VANFLYTA efficacy. Avoid concomitant use of VANFLYTA with strong or moderate CYP3A inducers. QT Interval–Prolonging Drugs VANFLYTA prolongs the QT/QTc interval. Coadministration of VANFLYTA with other drugs that prolong the QT interval may further increase the incidence of QT prolongation. Monitor patients more frequently with ECG if coadministration of VANFLYTA with drugs known to prolong the QT interval is required. Use in Specific Populations Pregnancy VANFLYTA can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Lactation Advise women not to breastfeed during treatment with VANFLYTA and for one month after the last dose. Females and Males of Reproductive Potential Pregnancy Testing Verify pregnancy status in females of reproductive potential within 7 days before starting treatment with VANFLYTA. Contraception Females Advise female patients of reproductive potential to use effective contraception during treatment with VANFLYTA and for 7 months after the last dose. Males Advise male patients with female partners of reproductive potential to use effective contraception during treatment with VANFLYTA and for 4 months after the last dose. Infertility Females Based on findings from animal studies, VANFLYTA may impair female fertility. These effects on fertility were reversible. Males Based on findings from animal studies, VANFLYTA may impair male fertility. These effects on fertility were reversible. Pediatric Use Safety and effectiveness of VANFLYTA have not been established in pediatric patients. Geriatric Use No overall differences in safety or efficacy were observed between patients 65 years of age and older and younger adult patients. Renal Impairment No dosage adjustment is recommended in patients with mild to moderate renal impairment (CLcr 30 to 89 mL/min). VANFLYTA has not been studied in patients with severe renal impairment (CLcr <30 mL/min). Hepatic Impairment No dosage adjustment is recommended in patients with mild hepatic impairment or moderate hepatic impairment. VANFLYTA has not been studied in patients with severe hepatic impairment. To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc, at 1-877-437-7763 or the FDA at 1-800-FDA-1088 or fda.gov/medwatch . Please see Full Prescribing Information , including Boxed WARNINGS, and Medication Guide . About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com . References 1 Kennedy VE, et al. Front Oncol . 2020;10:612880. 2 National Cancer Institute SEER Program. Cancer Stat Facts: Leukemia - Acute Myeloid Leukemia . 3 Loschi M, et al. Int J Mol Sci . 2021;22(11):5873. 4 Li Y, et al. Blood . 2004;104(4):1137-44. 5 Gilliand G and Griffin J. Blood. 1 September 2002;100:5 6 Montesinos P, et al. Abstract #1512 . ASH 2024 Annual Meeting. 7 Zhou Y, et al . Biomark Res . 2024;12(1):101. 8 Daver N, et al. 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