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VYXEOS Phase 3 trial in 309 adults (aged 60-75) with newly-diagnosed t-AML or AML-MRC1

Phase 3 study design: multicenter, open-label, active-controlled, randomized trial of VYXEOS vs 7+31,a

Phase 3 trial in adults with newly-diagnosed t-AML or AML-MRC: Part 1
Phase 3 trial in adults with newly-diagnosed t-AML or AML-MRC: Part 2
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A full VYXEOS course consists of up to 2 cycles of induction and up to 2 cycles of consolidation1

Key eligibility2

Previously untreated

Aged 60-75

Able to tolerate intensive therapy

PS 0-2

Primary endpoint1

Overall survival

  • VYXEOS was administered as 90-minute infusions1
  • Second induction was highly recommended for patients who did not achieve a response and was mandatory for patients achieving >50% reduction in percent blasts1
  • Postremission therapy with HSCT was permitted either in place of or after consolidation chemotherapy1
  • In the Phase 3 trial, a bone marrow assessment following induction was done between Days 14 and 213

‌aCytarabine 100 mg/m2 and daunorubicin 60 mg/m2.

VYXEOS studied in adults with newly-diagnosed t-AML or AML-MRC

In the VYXEOS Phase 3 trial, 15% of patients had a FLT3 gene mutation (n=43/279) and 9% had an NPM1 gene mutation (25/283)1

A diagnosis of t-AML or AML-MRC included1,4 309 AML patients
de novo AML with MDS-related cytogenetic abnormalities
Cytogenetic abnormalities characteristic of myelodysplasia
based on 2008 WHO criteria 		25%
AML with an antecedent hematological disorder 54%
Therapy-related AML
Prior cytotoxic therapy or ionizing radiotherapy for an unrelated disease 		20%

View patient cases for subtypes of secondary AML, including t-AML and AML-MRC

Patient characteristics were similar across the treatment arms1

Patient and disease characteristics1,2 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 0-1 138 (90) 134 (86)
PS 2 15 (10) 22 (14)
Cytogenetic risk Favorable 7 (5) 5 (3)
Intermediate 64 (42) 58 (38)
Poor 72 (47) 83 (53)

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.

Warning 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; ECOG=Eastern Cooperative Oncology Group; HSCT=hematopoietic stem cell transplant; MDS=myelodysplastic syndromes; PS=performance status; t-AML=therapy-related AML; WHO=World Health Organization.

References: 1. VYXEOS [package insert]. Palo Alto, CA: Jazz Pharmaceuticals. 2. 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. 3. Data on file. VYX-2018-003. Palo Alto, CA: Jazz Pharmaceuticals. 4. Data on file. VYX-2018-013. Palo Alto, CA: Jazz Pharmaceuticals.

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.