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The FDA approval of VYXEOS (CPX-351) was based on data from a large, pivotal, Phase 3 study1

The Phase 3 study was a multicenter, open-label, active-controlled, randomized trial of VYXEOS vs 7+3a in 309 patients (aged 60-75) with newly-diagnosed t-AML or AML-MRC2

Phase 3 dosing schedule: VYXEOS and 7+3 Phase 3 dosing schedule: VYXEOS and 7+3
IV infusion bag

A full VYXEOS course consists of up to 2 cycles of induction and up to 2 cycles of consolidation2

Key eligibility1,3,4

Previously untreated

Aged 60-75

Able to tolerate intensive therapy

ECOG PS 0-2

Primary endpoint2

Overall survival (OS)b

  • VYXEOS was administered as 90-minute infusions2
  • Second induction was highly recommended for patients who did not achieve a response and was mandatory for patients achieving >50% reduction in percent blasts2
  • Postremission therapy with HSCT was permitted either in place of or after consolidation chemotherapy2
  • In the Phase 3 trial, a bone marrow assessment following induction was done between Days 14 and 215
  • A preplanned overall survival analysis was conducted based on the final 5-year follow-up results from the Phase 3 trial3
Cytarabine 100 mg/m2 and daunorubicin 60 mg/m2.2
Overall survival was defined as date of randomization to death from any cause.2

VYXEOS was studied in older patients with newly-diagnosed sAML who often face a poor prognosis1,2,6

De novo AML with MDS-related cytogenetic abnormalities was defined as patients having cytogenetic abnormalities characteristic of myelodysplasia based on 2008 WHO criteria.1,7

View more information about t-AML and AML-MRC

sAML patient characteristics in the Phase 3 study

All patients in the Phase 3 study had difficult-to-treat sAML1,2

Baseline patient and disease characteristics1,2,8 VYXEOS
(N=153)
n (%)		 7+3
(N=156)
n (%)
Male/female 94/59 (61/39) 96/60 (62/38)
Median age (range) 68 (60, 75) 68 (60, 75)
ECOG
PS 0 37 (24) 45 (29)
PS 1 101 (66) 89 (57)
PS 2 15 (10) 22 (14)
All patients with prior HMA exposured 62 (41) 71 (46)
Number with cytogenetic risk by NCCN 143 146
Cytogenetic risk Favorable 7 (5) 5 (3)
Intermediate 64 (45) 58 (40)
Unfavorable 72 (50) 83 (57)
Genetic mutations FLT3 22 (14) 21 (14)
NPM1 13 (9) 12 (8)
CEBPA 12 (8) 5 (3)

41% of patients treated with VYXEOS had prior HMA exposure1

For patients >60 years old with AML, NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend selecting a treatment option based on patient performance status, comorbid conditions, and adverse features such as subtype rather than chronologic age alone9

Includes patients in the prespecified randomization strata of antecedent MDS with prior HMA exposure as well as patients in other strata (eg, t-AML, antecedent CMML) who had previously received HMAs.1

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

INDICATION

VYXEOS (daunorubicin and cytarabine) liposome for injection 44 mg/100 mg is indicated for the treatment of adults with newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC).

IMPORTANT SAFETY INFORMATION

WARNING: DO NOT INTERCHANGE WITH OTHER DAUNORUBICIN AND/OR CYTARABINE-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.

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

Hemorrhage

Serious or fatal hemorrhage events, including fatal CNS hemorrhages, associated with prolonged thrombocytopenia, have occurred with VYXEOS. The overall incidence (grade 1-5) of hemorrhagic events was 74% in the VYXEOS arm and 56% in the control arm. The most frequently reported hemorrhagic event was epistaxis (36% in VYXEOS arm and 18% in control arm). Grade 3 or greater events occurred in 12% of VYXEOS-treated patients and in 8% of patients in the control arm. Fatal treatment-emergent CNS hemorrhage not in the setting of progressive disease occurred in 2% of patients in the VYXEOS arm and in 0.7% of patients in the control arm. Monitor blood counts regularly and administer platelet transfusion support as required.

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 consolidation and as clinically required. Discontinue VYXEOS in patients with impaired cardiac function unless the benefit of initiating or continuing treatment outweighs the risk. VYXEOS is not recommended in patients with cardiac function that is less than normal.

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 cumulative 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

VYXEOS contains copper. Consult with a hepatologist and nephrologist with expertise in managing acute copper toxicity in patients with Wilson’s disease treated with VYXEOS. Monitor total serum copper, serum non-ceruloplasmin-bound copper, 24-hour urine copper levels, and serial 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. Discontinue in patients with signs or symptoms of acute copper toxicity.

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. If VYXEOS is used during pregnancy or if the patient becomes pregnant while taking VYXEOS, apprise the patient of the potential risk to a fetus. 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 hemorrhagic events (74%), febrile neutropenia (70%), rash (56%), edema (55%), nausea (49%), mucositis (48%), diarrhea (48%), constipation (42%), musculoskeletal pain (43%), fatigue (39%), abdominal pain (36%), dyspnea (36%), headache (35%), cough (35%), decreased appetite (33%), arrhythmia (31%), pneumonia (31%), bacteremia (29%), chills (27%), sleep disorders (26%), and vomiting (25%).

Please see full Prescribing Information, including BOXED Warning.

AML=acute myeloid leukemia; AML-MRC=AML with myelodysplasia-related changes; CMML=chronic myelomonocytic leukemia; ECOG=Eastern Cooperative Oncology Group; FDA=Food and Drug Administration; HMA=hypomethylating agent; HSCT=hematopoietic stem cell transplant; IV=intravenous; MDS=myelodysplastic syndromes; NCCN=National Comprehensive Cancer Network; PS=performance status; sAML=secondary AML; t-AML=therapy-related AML; WHO=World Health Organization.

References: 1. Lancet JE, Uy GL, Cortes JE, et al. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018;36(26):2684-2692. 2. VYXEOS [package insert]. Palo Alto, CA: Jazz Pharmaceuticals. 3. Lancet JE, Uy GL, Newell LF, et al. Five-year final results of a phase 3 study of CPX-351 versus 7+3 in older adults with newly diagnosed high-risk/secondary AML. Presented at: American Society of Clinical Oncology ASCO20 Virtual Scientific Program; May 29-31, 2020. Poster 283. 4. US National Institutes of Health. ClinicalTrials.gov. Phase III study of CPX-351 versus 7+3 in patients 60-75 years old with untreated high risk (secondary) acute myeloid leukemia (301). https://www.clinicaltrials.gov/ct2/show/NCT01696084. Last updated August 10, 2020. Accessed September 2, 2020. 5. Data on File (VYX-2018-003). Jazz Pharmaceuticals, Inc. 6. Granfeldt Østgård LS, Medeiros BC, Sengeløv H, et al. Epidemiology and clinical significance of secondary and therapy-related acute myeloid leukemia: a national population-based cohort study. J Clin Oncol. 2015;33(31):3641-3649. 7. Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937‐951. 8. Data on File (VYX-2018-013). Jazz Pharmaceuticals, Inc. 9. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.3.2020. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed December 23, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.

INDICATION

VYXEOS (daunorubicin and cytarabine) liposome for injection 44 mg/100 mg is indicated for the treatment of adults with newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC).

Important Safety Information

WARNING: DO NOT INTERCHANGE WITH OTHER DAUNORUBICIN AND/OR CYTARABINE-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.