General Information

Vyxeos is a liposomal combination of daunorubicin, an anthracycline topoisomerase inhibitor, and cytarabine, a nucleoside metabolic inhibitor.

Vyxeos is specifically indicated for the treatment of adults with newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). This indication was expanded in March of 2021 to include pediatric patients aged one year and older.

Vyxos is supplied as a liposome for intravenous infusion. The recommended dose schedule is as follows: Induction: Vyxeos (daunorubicin 44 mg/m2 and cytarabine 100 mg/m2) liposome via intravenous infusion over 90 minutes on days 1, 3, and 5 and on days 1 and 3 for subsequent cycles of induction, if needed. Consolidation: Vyxeos (daunorubicin 29 mg/m2 and cytarabine 65 mg/m2) liposome via intravenous infusion over 90 minutes on days 1 and 3.

Clinical Results

The FDA approval of Vyxeos was based on a pivotal Phase III clinical trial that evaluated the efficacy and safety of Vyxeos compared to cytarabine and daunorubicin (7+3) in 309 patients 60 to 75 years of age with newly diagnosed t-AML or AML-MRC. In the Vyxeos arm, patients received 44mg/100mg per m² (daunorubicin and cytarabine) liposome intravenously via a 90 minute infusion on days 1, 3 and 5 of induction (days 1 and 3 if a second induction was needed) and 29mg/65mg per m² (daunorubicin and cytarabine) liposome on days 1 and 3 for consolidation. Patients in the 7+3 arm received induction with cytarabine 100mg/m²/day on days 1-7 by continuous infusion and daunorubicin 60mg/m²/day on days 1-3. For consolidation, cytarabine was dosed on days 1-5 and daunorubicin on days 1-2. For the primary endpoint of overall survival, Vyxeos demonstrated an improvement that was superior to the 7+3 treatment regimen. The median overall survival for the Vyxeos treatment group was 9.6 months compared with 5.9 months for the 7+3 treatment group (p = 0.005; HR = 0.69 [0.52, 0.90]). Vyxeos also demonstrated a statistically significant improvement in complete response rate of 38 percent versus 26 percent; p=0.036. The overall, all-cause 30-day mortality was 6 percent in the Vyxeos arm and 11 percent in the control arm.

The FDA approval of Vyxeos for pediatric patients was based on safety data from two single-arm trials: AAML1421, conducted by the Children's Oncology Group (COG) and CPX-MA-1201, conducted by Cincinnati Children's Hospital (CCH) and evidence of effectiveness from the above study in adults. Thirty-eight pediatric patients aged one to 21 years of age with AML in first relapse were enrolled in the Phase 1/2 AAML1421 study, and 27 patients aged one to 19 years with relapsed/refractory hematologic malignancies were enrolled in the Phase 1 CPX-MA-1201 study. Both studies found no differences in the safety profile based on age. The use of Vyxeos for this indication is supported by evidence of effectiveness from study CPX351-301 in adult patients.

Side Effects

Adverse effects associated with the use of Vyxeos may include, but are not limited to, the following:

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

vomiting

The Vyxeos drug label comes with the following Black Box 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 error.

Mechanism of Action

Vyxeos is a liposomal combination of daunorubicin, an anthracycline topoisomerase inhibitor, and cytarabine, a nucleoside metabolic inhibitor. Daunorubicin has antimitotic and cytotoxic activity, which is achieved by forming complexes with DNA, inhibiting topoisomerase II activity, inhibiting DNA polymerase activity, affecting regulation of gene expression, and producing DNA-damaging free radicals. Cytarabine is a cell cycle phase-specific antineoplastic agent, affecting cells only during the S-phase of cell division. Cytarabine acts primarily through inhibition of DNA polymerase.