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Transcript

[Narrator]
VYXEOS (daunorubicin and cytarabine) 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).

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.

VYXEOS is contraindicated in patients with a history of serious hypersensitivity reactions to cytarabine, daunorubicin, or any component of the formulation.

[Dr. Powell]
Hi. I’m Dr. Bayard Powell, and I am a Phase 3 clinical investigator for VYXEOS.

Following years of extensive preclinical and clinical research, we conducted the pivotal Phase 3 trial of VYXEOS in patients with secondary acute myeloid leukemia (AML). These data were published in the Journal of Clinical Oncology.

Historically, developing new treatment options for patients with secondary AML has been challenging. The 7+3 chemotherapy regimen has been the standard of care for AML induction therapy for more than 40 years.

Secondary AML subtypes such as therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC), occur in approximately one-third of all AML cases. These subtypes are associated with particularly low survival outcomes.

However, I’m quite excited to be able to share key data from the published Phase 3 study, where we evaluated the efficacy and safety of VYXEOS compared to the standard 7+3 regimen in adults with newly-diagnosed t-AML and AML-MRC.

[Narrator]
VYXEOS liposomes were designed for simultaneous delivery of daunorubicin and cytarabine at a fixed one to five molar ratio over a prolonged period of time. This ratio was shown to be synergistic at killing leukemia cells in preclinical studies.

[Dr. Powell]
The published Phase 3 study for VYXEOS was based on experience that we gained from a prior randomized Phase 2 study in patients with secondary AML.

This pivotal Phase 3 study was a multicenter, open-label, active-controlled randomized trial that compared the efficacy and safety of VYXEOS to the 7+3 regimen in 309 patients with secondary AML between the ages of 60 and 75.

It was this trial that led to the FDA approval of VYXEOS for the treatment of adults with newly-diagnosed secondary AML subtypes t-AML or AML-MRC.

This trial included newly-diagnosed patients with secondary AML such as de novo AML with MDS-related cytogenetic abnormalities, AML with antecedent hematologic disorder, and therapy-related AML.

Other eligibility criteria included previously untreated AML, ability to tolerate intensive chemotherapy, and an ECOG performance status between 0 and 2.

In this study, 15% of patients tested had a FLT3 gene mutation and 9% had an NPM1 gene mutation.

Overall, patient characteristics were similar across the treatment arms.

For each treatment arm, patients could receive up to 2 cycles of induction therapy to achieve complete remission or complete remission with incomplete neutrophil or platelet recovery, followed by up to 2 cycles of consolidation therapy.

The initial VYXEOS induction was administered as a 90-minute infusion on days 1, 3, and 5.

A second induction of VYXEOS was administered on days 1 and 3 for patients who did not achieve remission.

It was mandatory for patients who achieved greater than 50% reduction in percent blasts.

Postremission stem cell transplant was permitted in place of or following consolidation.

A higher proportion of VYXEOS-treated patients achieved remission and proceeded to receive the first consolidation (32%) and second consolidation (15%) compared to the 7+3 arm (21.2% and 7.9%, respectively).

Furthermore, the primary endpoint was overall survival. Safety outcomes were adverse events, lab assessments, and 30-day and 60-day mortality.

Efficacy analyses were performed in the intent-to-treat population. Safety was evaluated in all treated patients.

Survival was analyzed after 236 deaths occurred (104 in the VYXEOS arm and 132 in the 7+3 arm) with a median follow-up of 20.7 months.

This study established that VYXEOS is the first chemotherapy to demonstrate superior overall survival of 9.6 months versus 5.9 months for the 7+3 cohort in adults with newly-diagnosed secondary AML subtypes t-AML or AML-MRC.

Additionally, the Kaplan-Meier estimated 1-year survival of 42% was observed in VYXEOS-treated patients versus 28% for patients treated with 7+3.

VYXEOS also demonstrated a significant improvement in complete response compared to 7+3; 38% versus 26%.

More patients treated with VYXEOS also received post-treatment stem cell transplant compared to 7+3; 34% versus 25%.

Now let’s review some safety data.

As shown here, reported adverse reactions were generally consistent with the known safety profile of daunorubicin and cytarabine therapy.

Fatal treatment-emergent CNS hemorrhage 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.

VYXEOS was also associated with lower 30- and 60-day mortality rates compared to 7+3.

A published Phase 3 trial showed that VYXEOS had greater overall survival than the 7+3 regimen in newly-diagnosed AML patients with secondary AML subtypes t-AML and AML-MRC.

Collectively, these data led to the FDA approval of VYXEOS in this patient population, providing an exciting option in the treatment arsenal for these challenging patients with secondary AML.

Thank you and have a pleasant day.

[Narrator]

  • Serious or fatal hemorrhage events, including fatal CNS hemorrhages, associated with prolonged severe thrombocytopenia, have occurred in patients treated with VYXEOS. Monitor blood counts regularly and administer platelet transfusion support as required.
  • VYXEOS contains daunorubicin, which has a known risk of cardiotoxicity. Assess cardiac function before, during, and after treatment as clinically indicated. Discontinue in patients with impaired cardiac function unless the benefit of treatment outweighs the risk. VYXEOS treatment is not recommended in patients with cardiac function that is less than normal. Calculate the lifetime cumulative anthracycline exposure prior to each cycle of VYXEOS. VYXEOS is not recommended in patients who have reached the maximum lifetime anthracycline dose limit.
  • If a severe or life-threatening hypersensitivity reaction occurs, discontinue VYXEOS permanently, treat according to the standard of care, and monitor until signs and symptoms resolve.
  • VYXEOS contains copper and has the potential to cause copper overload in patients with Wilson’s disease or other copper-related metabolic disorders. Monitor patients and use only if the benefits outweigh the risks. Discontinue in patients with signs or symptoms of acute copper toxicity.
  • Daunorubicin has been associated with severe local tissue necrosis at the site of drug extravasation. Administer VYXEOS by the intravenous route only.
  • VYXEOS can cause fetal harm. Advise females and males of reproductive potential of the potential risk to a fetus and to use effective contraception.

The most common adverse reactions (incidence ≥25%) were hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, 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 newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC).

IMPORTANT SAFETY INFORMATION

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.