Announcing the approval of new option in AML
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The first chemotherapy to demonstrate superior overall survival vs 7+3 in adults with t-AML and AML-MRC1
IMPORTANT SAFETY INFORMATION
WARNING: DO NOT INTERCHANGE WITH OTHER CYTARABINE- AND/OR DAUNORUBICIN-CONTAINING PRODUCTS
VYXEOS has different dosage recommendations than daunorubicin hydrochloride injection, cytarabine injection, daunorubicin citrate liposome injection, and cytarabine liposome injection. Verify drug name and dose prior to preparation and administration to avoid dosing errors.
Important Safety Information continues below.
Dear Healthcare Provider:
Jazz Pharmaceuticals is proud to announce that VYXEOS has been approved by the US Food and Drug Administration (FDA) for the treatment of adults with therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC).
In a Phase 3 trial including 309 t-AML or AML-MRC patients, median overall survival was 9.6 months for VYXEOS versus 5.9 months for 7+3 (P=0.005)1
Kaplan-Meier curve for overall survival, ITT population1
Kaplan-Meier curve for overall survival, ITT population
Study Design1
The Phase 3 study was a randomized, multicenter, open-label, active-controlled superiority study of VYXEOS versus cytarabine and daunorubicin (7+3) in patients 60 to 75 years of age with newly diagnosed t-AML or AML-MRC. There were 153 patients randomized to VYXEOS and 156 patients randomized to the 7+3 arm. 20% had t-AML, 54% had AML with prior MDS, and 25% had de novo AML with MDS-related cytogenetic abnormalities. Efficacy was established on the basis of overall survival from the date of randomization to death from any cause.
VYXEOS 44 mg/100 mg per m2 was given intravenously on Days 1, 3, and 5 for first induction and on Days 1 and 3 for those needing a second induction. For consolidation, the VYXEOS dose was 29 mg/65 mg per m2 on Days 1 and 3. In the 7+3 arm, first induction was cytarabine 100 mg/m2 on Days 1-7 by continuous infusion + daunorubicin 60 mg/m2 on Days 1-3. For second induction and consolidation, cytarabine was dosed on Days 1-5 and daunorubicin on Days 1 and 2.

 
For information about reimbursement, ordering, and more, visit vyxeos.com.
VYXEOS is the first dual-drug liposomal encapsulation of daunorubicin and cytarabine in a fixed 1:5 molar ratio. This 1:5 molar ratio of daunorubicin and cytarabine was shown to be synergistic in killing leukemia cells in vitro and in murine models.1
VYXEOS demonstrated a statistically significant improvement in CRa (37% vs 26%, P=0.04) rates versus 7+3, and a higher percentage of patients were able to receive a hematopoietic stem cell transplant (HSCT) with VYXEOS (34%) compared to 7+3 (25%).1
IMPORTANT SAFETY INFORMATION
Contraindications
VYXEOS is contraindicated in patients with a history of serious hypersensitivity reactions to cytarabine, daunorubicin, or any component of the formulation.
Warnings and Precautions
Severe Myelosuppressive-Related Toxicities
Severe myelosuppression occurs after administration of VYXEOS. Time to recovery of absolute neutrophil count (ANC) and platelets may be prolonged and require additional monitoring. Fatal central nervous system hemorrhages not in the setting of progressive disease occurred in 2% of patients in the VYXEOS arm and 0.7% of patients in the control arm. Fatal infections in the absence of progressive disease occurred in 5% and 3% of patients in the VYXEOS arm and control arm, respectively. Monitor blood counts regularly until recovery. If myelosuppressive complications occur, use appropriate supportive measures.
Cardiotoxicity
VYXEOS contains daunorubicin, which has a known risk of cardiotoxicity. This risk may be increased in patients with prior anthracycline therapy, preexisting cardiac disease, previous radiotherapy to the mediastinum, or concomitant use of cardiotoxic drugs. Assess cardiac function prior to VYXEOS treatment and repeat prior to each cycle as clinically required. VYXEOS is not recommended in patients with impaired cardiac function unless the benefit of treatment outweighs the risk.
Total cumulative doses of non-liposomal daunorubicin greater than 550 mg/m2 have been associated with an increased incidence of drug-induced congestive heart failure. The tolerable limit appears lower (400 mg/m2) in patients who received radiation therapy to the mediastinum. Calculate the lifetime cumulative anthracycline exposure prior to each cycle of VYXEOS. VYXEOS is not recommended in patients whose lifetime anthracycline exposure has reached the maximum lifetime dose limit.
Hypersensitivity Reactions
Serious or fatal hypersensitivity reactions, including anaphylactic reactions, have been reported with daunorubicin and cytarabine. Monitor patients for hypersensitivity reactions. If a mild or moderate hypersensitivity reaction occurs, interrupt or slow the rate of infusion with VYXEOS and manage symptoms. If a severe or life-threatening hypersensitivity reaction occurs, discontinue VYXEOS permanently, treat the symptoms, and monitor until symptoms resolve.
Copper Overload in Patients With Wilson's Disease or Other Copper-Related Metabolic Disorders
VYXEOS contains copper. Monitor total serum copper, ceruloplasmin, 24-hour urine copper levels, and neuropsychological examinations during VYXEOS treatment in patients with Wilson's disease or other copper-related metabolic disorders. Use only if the benefits outweigh the risks.
Tissue Necrosis
Daunorubicin has been associated with severe local tissue necrosis at the site of drug extravasation. Administer VYXEOS by the intravenous route only. Do not administer by intramuscular or subcutaneous route.
Embryo-Fetal Toxicity
VYXEOS can cause embryo-fetal harm when administered to a pregnant woman. Patients should avoid becoming pregnant while taking VYXEOS. Advise females and males of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of VYXEOS.
MOST COMMON ADVERSE REACTIONS
The most common adverse reactions (incidence ≥25%) were febrile neutropenia, hemorrhagic events, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, dyspnea, headache, cough, arrhythmia, decreased appetite, pneumonia, cardiotoxicity, chills, sleep disorders, and vomiting.
INDICATION
VYXEOS (daunorubicin and cytarabine) liposome for injection 44 mg/100 mg is indicated for the treatment of adults with therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC).
Please see full Prescribing Information, including Boxed Warning, for VYXEOS.
For VYXEOS ordering information or to learn more, visit vyxeos.com or talk to your oncology account manager.
aComplete remission (CR) was a secondary endpoint and was defined as bone marrow blasts <5%, absence of blasts with Auer rods, absence of extramedullary disease, absolute neutrophil count >1.0 x 109/L (1000/μL), platelet count >100 x 109/L (100,000/μL), and independence from red cell transfusions.2
CI=confidence interval; ITT=intent to treat; MDS=myelodysplastic syndromes.
References:
  1. VYXEOS [package insert]. Palo Alto, CA: Jazz Pharmaceuticals.
  2. Data on file. VYX-2017-XXX. Palo Alto, CA: Jazz Pharmaceuticals
Medical inquiries about VYXEOS may be directed to our Medical Information department at 1-800-520-5568 or via email to jazzpharma@medcomsol.com.