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Efficacy Safety Real-World Evidence

Efficacy

The only choice for more than double the 5-year OS vs 7+31

Median OS (primary analysis) of
9.6 months with VYXEOS vs 5.9 months with 7+3, reducing the risk of death
by 31% (HR=0.69 [95% CI: 0.52, 0.90], P=0.005 [P value is 2 sided])2

Reprinted from Lancet Haematol, volume 8, issue 7, Lancet JE et al, CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial, pages e481-e491, copyright 2021, with permission from Elsevier. https://www.thelancet.com/journals/lanhae/home

Phase 3 Clinical Study Review video-icon
Phase 3 Study Design
This prospectively planned OS analysis of the ITT population was conducted based on the final 5-year follow-up results from the Phase 3 study. This prospectively planned OS analysis of the ITT population was conducted based on the final 5-year follow-up results from the Phase 3 study.

This prospectively planned OS analysis of the ITT population was conducted based on the final
5-year follow-up results from the Phase 3 study.1

  • CR/CRi
  • CR/CRi OS
  • HSCT
  • HSCT OS
  • Non-HSCT OS
  • OS by Age
CR/CRi arrow

Give your patients the best chance at remission2,3

In the Phase 3 study, almost half of patients with sAML treated with VYXEOS achieved CR+CRi.2,3

Nearly 50% of patients treated with VYXEOS achieved overall
remission (CR+CRi).2,3

Percentage of patients with sAML
who achieved CR and CR+CRi2,3

CR-CR1 CR-CR2

Early remissions may be possible—55% (58/105) of patients treated with VYXEOS achieved remission after 1 induction cycle.3

Percentage of patients with sAML
who achieved CR+CRi3

CR-CR3 CR-CR4
CR/CRi OS arrow
Exploratory post hoc analysis

VYXEOS delivers remission that can lead to greater survival:
longer 5-year median OS for patients with CR/CRi4

Kaplan-Meier curve for OS in patients who achieved CR or CRi Kaplan-Meier curve for OS in patients who achieved CR or CRi

MEDIAN OS (95% CI):

VYXEOS:
21.7 months (CI: 13.0, 29.7)
(n=50/73)
7+3:
10.4 months (CI: 7.8, 15.2)
(n=43/52)

Reprinted from Lancet Haematol, volume 8, issue 7, Lancet JE et al, CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial, pages e481-e491, copyright 2021, with permission from Elsevier. https://www.thelancet.com/journals/lanhae/home

Limitations of subanalysis

  • This exploratory post hoc subgroup analysis was not powered to determine statistical significance. No efficacy conclusions about OS can be drawn from this analysis
  • Results should be interpreted with caution, as this analysis was not prespecified and was conducted in a small, nonrandomized subgroup (n=125)
  • The treatment effect of this nonrandomized subgroup was possibly confounded by unbalanced baseline characteristics
HSCT arrow

When transplant is the goal, VYXEOS helps
more patients reach HSCT1,5

Data from the Phase 3 study showed that more patients with sAML reached HSCT with VYXEOS vs 7+3.1

Overall rate of HSCT1,a

aFirst CR, induction failure, or as salvage after relapse.2

A greater proportion of patients with sAML who achieved first CR with VYXEOS subsequently underwent HSCT vs 7+3.5

Rate of HSCT during first CR2,5,b

bFirst CR after 1 or 2 induction cycles.5

The foundation of sAML treatment is intensive chemotherapy,
with the ultimate goal of achieving remission and reaching HSCT6,7

HSCT OS arrow

Exploratory post hoc analysis

Starting with VYXEOS can lead to prolonged
survival after HSCT1,4

More than double the 3-year OSa post HSCT for patients treated with VYXEOS (56%) vs 7+3 (23%).1

Analysis 1: Kaplan-Meier curve for OS landmarked from time of HSCT1

Kaplan-Meier curve for OS landmarked from time of HSCT

MEDIAN OS (95% CI)1:

VYXEOS:
Not reached (16.2, NR)
(n=23/53)
7+3:
10.3 months (6.2, 16.7)
(n=30/39)

Analysis 2: Kaplan-Meier curve for OS landmarked from time of HSCT in patients who achieved CR or CRi4

Kaplan-Meier curve for OS landmarked from time of HSCT in patients who achieved CR or CRi

MEDIAN OS (95% CI)4:

VYXEOS:
Not reached (15.6, NR)
(n=19/41)
7+3:
11.7 months (4.6, 24.3)
(n=17/24)

aBased on Kaplan-Meier estimates.

Reprinted from Lancet Haematol, volume 8, issue 7, Lancet JE et al, CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial, pages e481-e491, copyright 2021, with permission from Elsevier. https://www.thelancet.com/journals/lanhae/home

5-year Kaplan-Meier estimates from date of HSCT were not available,
as the follow-up time from date of HSCT was less than 5 years1

Limitations of subanalyses1,4

  • These exploratory post hoc subgroup analyses were not powered to determine statistical significance. No efficacy conclusions about OS following HSCT or OS following HSCT after CR or CRi can be drawn from these analyses
  • Results should be interpreted with caution, as these analyses were not prespecified and were conducted in small, nonrandomized subgroups (Analysis 1, n=92; Analysis 2, n=65)
  • The treatment effect of this nonrandomized subgroup was possibly confounded by unbalanced baseline characteristics
  • A higher proportion of patients proceeding to HSCT in the VYXEOS arm (75%) were in CR/CRi as compared with the 7+3 arm (62%)
  • To address this limitation, Analysis 2 evaluated only those patients in each treatment arm who were in CR/CRi at the time they received HSCT
Non-HSCT OS arrow

Exploratory post hoc analysis

VYXEOS can increase the chance of survival in patients
unable to undergo transplant8

Median OS for non-HSCT
patients who archived CR

Median OS for non-HSCT
patients who archived CR+CRi

Limitations of subanalysis

  • This subgroup analysis was exploratory and not powered to determine statistical significance. No efficacy conclusions about OS following CR or CRi can be drawn from this analysis
  • Results should be interpreted with caution, as this analysis was not prespecified and was conducted in a small, nonrandomized subgroup (n=61)
  • The treatment effect of this nonrandomized subgroup was possibly confounded by unbalanced baseline characteristics
OS by Age arrow

Exploratory post hoc analysis

Consider VYXEOS in your older patients with sAML:
longer 5-year median OS in patients aged 60-69 and 70-75 years4

Kaplan-Meier curve for OS by age subgroup, aged 60 to 69 years

Kaplan-Meier curve for OS landmarked from time of HSCT

MEDIAN OS (95% CI):

VYXEOS:
9.6 months (6.0, 12.6)
(n=76/96)
7+3:
6.9 months (4.6, 8.8)
(n=91/102)

Kaplan-Meier curve for OS by age subgroup, aged 70 to 75 years

Kaplan-Meier curve for OS landmarked from time of HSCT in patients who achieved CR or CRi

MEDIAN OS (95% CI):

VYXEOS:
8.9 months (4.7, 12.2)
(n=48/57)
7+3:
5.6 months (3.3, 7.5)
(n=54/54)

Reprinted from Lancet Haematol, volume 8, issue 7, Lancet JE et al, CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial, pages e481-e491, copyright 2021, with permission from Elsevier. https://www.thelancet.com/journals/lanhae/home

Limitations of subanalyses

  • These exploratory post hoc subgroup analyses were not powered to determine statistical significance. No efficacy conclusions about OS can be drawn from these analyses
Phase 3 Study Safety Profile arrow-right
Study design

VYXEOS is the only FDA-approved treatment for sAML demonstrating superior overall survivala in a Phase 3 study3,9,b

The Phase 3 study was a multicenter, open-label, active-controlled, randomized (1:1) trial of VYXEOS vs 7+3 in 309 patients (aged 60-75 years) with newly diagnosed sAML.2,3

VYXEOS (n=153)

(daunorubicin 44 mg/m2 and cytarabine 100 mg/m2)
liposome given via IV infusion

VYXEOS

(daunorubicin 29 mg/m2 and cytarabine 65 mg/m2)
liposome given via IV infusion

  • First induction
    (required)
    Days 1, 3, & 5
  • Second induction
    (if needed)
    Days 1 & 3
    triangle
  • First consolidation
    (if needed)
    Days 1 & 3
    triangle
  • Second consolidation
    (if needed)
    Days 1 & 3
    triangle

7+3 (n=156)

(cytarabine 100 mg/m2/day by continuous infusion and daunorubicin 60 mg/m2/day)

  • First induction
    (required)
    Cytarabine: Days 1-7
    Daunorubicin: Days 1-3
  • Second induction
    (if needed)
    Cytarabine: Days 1-5
    Daunorubicin: Days 1 & 2
    triangle
  • First consolidation
    (if needed)
    Cytarabine: Days 1-5
    Daunorubicin: Days 1 & 2
    triangle
  • Second consolidation
    (if needed)
    Cytarabine: Days 1-5
    Daunorubicin: Days 1 & 2
    triangle

VYXEOS (n=153)


(daunorubicin 44 mg/m2 and cytarabine 100 mg/m2) liposome given via IV infusion

  • First induction
    (required)
    Days 1, 3, & 5
  • Second induction
    (if needed)
    Days 1 & 3
    triangle

VYXEOS


(daunorubicin 29 mg/m2 and cytarabine 65 mg/m2)
liposome given via IV infusion

  • First consolidation
    (if needed)
    Days 1 & 3
  • Second consolidation
    (if needed)
    Days 1 & 3
    triangle

7+3 (n=156)


(cytarabine 100 mg/m2/day by continuous infusion and daunorubicin 60 mg/m2/day)

  • First induction
    (required)
    Cytarabine:
    Days 1-7
    Daunorubicin: Days 1-3
  • Second induction
    (if needed)
    Cytarabine:
    Days 1-5
    Daunorubicin: Days 1 & 2
    triangle
  • First consolidation
    (if needed)
    Cytarabine:
    Days 1-5
    Daunorubicin: Days 1 & 2
  • Second consolidation
    (if needed)
    Cytarabine:
    Days 1-5
    Daunorubicin: Days 1 & 2
    triangle

All patients in the Phase 3 study
faced a poor prognosis1,2

Diagnosed with therapy-related AML

Diagnosed with
therapy-related AML

Diagnosed with de novo AML-MDS

Diagnosed with
de novo AML-MDS

Diagnosed with AML-MRC

Diagnosed with AML-MRC

Patient Demographics Learn About High-risk sAML arrow-right

VYXEOS was proven in the largest Phase 3 study of patients with sAML to date.3,9

Key details1-4:

  • Primary endpoint: OS
  • Median follow-up: 20.7 months
  • VYXEOS was administered as 90-minute infusions
  • Second induction was highly recommended for patients who did not achieve a response and was mandatory for patients achieving >50% reduction in percent blasts
  • Postremission therapy with HSCT was permitted either in place of or after consolidation chemotherapy
  • In the Phase 3 study, a bone marrow assessment following induction was done between Days 14 and 21
  • A prospectively planned OS analysis of the ITT population was conducted based on the final 5-year follow-up results from the Phase 3 study.
    Exploratory post hoc subgroup analyses were also conducted

Eligibility criteria1:

  • Previously untreated
  • Aged 60-75 years
  • Able to tolerate intensive therapy
  • ECOG PS 0-2

AML=acute myeloid leukemia; CR=complete remission; CRi=complete remission with incomplete count recovery; ECOG PS=Eastern Cooperative Oncology Group Performance Status; FDA=US Food and Drug Administration; HR=hazard ratio; ITT=intent-to-treat; IV=intravenous; MDS=myelodysplastic syndromes; MRC=myelodysplasia-related changes.


aVs 7+3: cytarabine 100 mg/m2 and daunorubicin
60 mg/m2.3


bEvaluating the largest sAML population assessed in clinical studies of FDA-approved AML therapies.9

Outpatient Strategies

Some patients may be appropriate for outpatient administration of VYXEOS, giving you more options when planning their treatment. Read how some institutions are approaching outpatient use of VYXEOS.

more arrow-right

About sAML

Secondary AML is a broad category of high-risk AML that includes multiple subtypes of leukemias with different characteristics but similar poor prognosis and significant challenge to reach a cure.7,10 Learn more about which patients may be appropriate for intensive chemotherapy with VYXEOS.

more arrow-right
INDICATION Close

VYXEOS is indicated for the treatment of newly-diagnosed therapy-related acute myeloid leukemia (t‑AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients 1 year and older.

Important Safety Information Open Close

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. Confirm patency of intravenous access before administration. 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%) are 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.

References: 1. Lancet JE, Uy GL, Newell LF, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021;8(7):e481-e491. 2. VYXEOS [package insert]. Palo Alto, CA: Jazz Pharmaceuticals. 3. 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.
4. Supplement to: Lancet JE, Uy GL, Newell LF, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021;8(7):e481-e491. 5. Lin TL, Medeiros BC, Uy GL, et al. Outcomes by number of induction cycles with CPX-351 vs 7+3 chemotherapy in older adults with newly diagnosed high-risk/secondary acute myeloid leukemia (sAML). Presented at: American Society of Clinical Oncology Annual Meeting; June 1-5, 2018; Chicago, IL. Poster 7040.
6. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.2.2024. ©National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed April 3, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. 7. Lalayanni C, Gavriilaki E, Athanasiadou A, et al. Secondary acute myeloid leukemia (sAML): similarly dismal outcomes of AML after an antecedent hematologic disorder and therapy related AML. Clin Lymphoma Myeloma Leuk. 2022;22(4):e233-e240. 8. Lin TL, Rizzieri DA, Ryan DH, et al. Older adults with newly diagnosed high-risk/secondary AML who achieved remission with CPX-351: phase 3 post hoc analyses. Blood Adv. 2021;5(6):1719-1728. 9. Data on File (VYX-2022-047). Jazz Pharmaceuticals, Inc. 10. Capelli D, Menotti D, Florentini A, Sarcani F, Olivieri A. Chapter 7: Secondary acute myeloid leukemia: pathogenesis and treatment. Accessed March 21, 2024. https://www.ncbi.nlm.nih.gov /books /NBK586211 /?report=printable

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