FDA Approves Vyxeos for Two Leukemia Types

Vyxeos (CPX-351), a fixed-combination of daunorubicin and cytarabine, was granted FDA approval for the treatment of adults with newly diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). The approval came from an improvement in overall survival (OS) in a phase 3 study.

The approval, which arrived several months ahead of an FDA deadline, was based on findings from a phase 3 study comparing Vyxeos with the traditional cytarabine and daunorubicin (7+3) for patients with newly diagnosed t-AML or AML-MRC. In the study, the median OS was 9.56 months with Vyxeos versus 5.95 months with 7+3, representing a 31 percent reduction in the risk of death.

“This is the first approved treatment specifically for patients with certain types of high-risk AML,” Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement. “Vyxeos combines two commonly used chemotherapies into a single formulation that may help some patients live longer than if they were to receive the two therapies separately.”

VYXEOS is a liposomal bound coformulation of cytarabine and daunorubicin that delivers the two medications in a 5-1molar ratio. The phase 3 trial consisted of 309 patients aged 60 to 75 who were stratified evenly between each arm into groups aged 60 to 69 (198 patients) or from 70 to 75 (111 patients). Patient characteristics were well-balanced between the 2 arms and groups.

Patients were randomized to receive Vyxeos (153 patients) or 7+3 (156 patients). In the first induction phase, Vyxeos was administered at a first induction dose of 100 u/m² on days one, three and five. In the 7+3 arm, cytarabine was given at 100 mg/m² daily for seven days, followed by 60 mg/m² of daunorubicin on days one, two and three. In the second induction portion, VYXEOS was given at 100 u/m² on days one and three and in the 7+3 group cytarabine was given at 100 mg/m² daily for five days with 60 mg/m² of daunorubicin on days one and two.

The complete response (CR) or CR with incomplete platelet or neutrophil recovery (CRi) rate was 47.7 percent versus 33.3 percent for Vyxeos and 7+3, respectively. For CR alone, the rates were 37.3 percent for Vyxeos and 25.6 percent for 7+3.

At 12 months, the OS rate was 41.5 percent in the Vyxeos arm versus 27.6 percent in the 7+3 group. At 24 months, 31.1 percent of patients enrolled in the Vyxeos arm of the study remained alive compared with 12.3 percent with 7+3. The median event-free survival was 2.53 months with VYXEOS compared with 1.31 months with 7+3.

In an exploratory analysis of the phase 3 study for those with secondary, untreated AML, 34 of the 52 patients (65 percent) in the Vyxeos arm who proceeded to transplant remained alive after a median follow-up of 521 days. In the 7+3 arm, after 442 days of follow-up, 13 of 39 patients remained alive (33 percent).

From the time of transplant, the median OS was not reached in the Vyxeos arm versus 10.25 months for 7+3, representing a 54 percent reduction in the risk of death. Furthermore, 100 days after transplant, the rate of mortality from any cause was 53 percent lower in the Vyxeosarm versus 7+3.

The rates of grade 3 to 5 nonhematologic adverse events (AEs) were similar between the two arms. Common grade 3 to 5 AEs occurring in the two arms included febrile neutropenia (68 percent with Vyxeos vs 71 percent with 7+3), pneumonia (20 percent vs 15 percent), hypoxia (13 percent vs 15 percent), sepsis (9 percent vs 7 percent), hypertension (10 percent vs 5 percent), respiratory failure (7 percent each), fatigue (7 percent vs 6 percent), bacteremia (10 percent vs 2 percent) and ejection fraction decreased (5 percent each).

Vyxeos, which is being marketing by Jazz Pharmaceuticals, was approved with a boxed warning advising against interchanging the medication with other daunorubicin- and/or cytarabine-containing products. The FDA also advised against using Vyxeos in patients with a history of serious hypersensitivity to daunorubicin, cytarabine or any component of the formulation.