New Drug Granted a Priority Review for AML Treatment

VYXEOS (CPX-351), a novel injection, was granted a new drug application (NDA) by the Food and Drug Administration (FDA), granting the drug a priority review for the treatment of acute myeloid leukemia (AML), according to Jazz Pharmaceuticals, the producer of the drug.

Priority review status is designated for drugs that may offer major advances in treatment or provide a treatment where no adequate therapy exists. The designation accelerates the timing of the FDA review of the application compared with a standard review.

“We are pleased by the FDA’s acceptance of the NDA filing with priority review as this action emphasizes the need for new treatments for patients living with AML,” Jazz executive vice president and chief medical officer Karen Smith, M.D., Ph.D., said in a statement. “We look forward to working with the FDA during this review process to obtain approval of Vyxeos as quickly as possible, as AML is the most common of all adult leukemias and AML patients have among the lowest survival rates.”

The NDA submission includes clinical data from five studies, including data from the pivotal phase 3 study comparing the formulation with cytarabine and daunorubicin (7+3) were presented at last year’s American Society of Clinical Oncology (ASCO) Annual Meeting. At the time, principal investigator Jeffrey E. Lancet, M.D., senior member and chief of the Leukemia/Myelodysplasia Program at Moffitt Cancer Center, said the formulation, “should be considered standard first-line treatment for older patients with high-risk AML.”

Those phase 3 results showed that VYXEOS reduced the risk of death by 31 percent compared with 7+3 for older patients with high-risk, secondary AML. The formulation showed a median overall survival of 9.56 months versus 5.95 months with 7+3.

At 12 months, 41.5 percent of patients enrolled in the VYXEOS arm were alive versus 27.6 percent in the 7+3 arm. 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.

Median event-free survival was 2.53 months with VYXEOS versus 1.31 months (1.08-1.64) with 7+3.

The randomized, controlled phase 3 trial included 309 patients across 39 sites throughout both the United States and Canada who were between the ages of 60 and 75. Patients enrolled in the study were split into either an age group consisting of patients between the ages of 60 to 69 or from 70 to 75.

Patients were randomly assigned to VYXEOS (153 patients) or 7+3 (156 patients). Patients in the VYXEOS arm were given a first induction of 100 u/m2 on days one, three and five. Patients in the control arm received 100 mg/m2 of cytarabine daily for seven days, followed by 60 mg/m2 of daunorubicin on days one, two and three.

Second induction for patients enrolled in the VYXEOS arm was 100 u/m2 on days one and three, while patients receiving conventional cytarabine and daunorubicin were given 100 mg/m2 of daily cytarabine for fuve days with 60 mg/m2 of daunorubicin on days one and two.

Induction response rates (complete remission [CR] plus CR with incomplete hematologic recovery) were 47.7 percent for VYXEOS versus 33.3 percent for 7+3, yielding a relative benefit of 43.2 percent with the investigational treatment. For CR alone, the rates were 37.3 percent and 25.6 percent, between VYXEOS and 7+3, respectively.

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).

Based on these data, the FDA previously granted VYXEOS a breakthrough therapy designation as a treatment for patients with therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC).

The FDA granted VYXEOS fast track status for the treatment of elderly patients with secondary AML in January 2015. That decision was based on results from a pair of phase 2 studies in which VYXEOS showed promising results for patients with newly diagnosed and relapsed AML.