Image by Lance Liotta
AML cells
The European Medicines Agency’s Committee for Medicinal Products for Human Use has granted accelerated assessment to a marketing authorization application (MAA) for CPX-351 (Vyxeos™), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.
The MAA is for CPX-351 to treat adults with high-risk acute myeloid leukemia (AML), defined as therapy-related AML or AML with myelodysplasia-related changes.
Accelerated assessment is designed to reduce the review timeline for products of major interest for public health and therapeutic innovation.
“If approved, Vyxeos will become the first new chemotherapy treatment option specifically for European patients with therapy-related AML or AML with myelodysplasia-related changes,” said Karen Smith, MD, PhD, executive vice president, research and development and chief medical officer at Jazz Pharmaceuticals, the company developing and marketing CPX-351.
The MAA for CPX-351 is supported by clinical data from 5 studies, including a phase 3 study. Results from this study were presented at the 2016 ASCO Annual Meeting.
In this study, researchers compared CPX-351 to cytarabine and daunorubicin (7+3) in 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.
The complete response rate was 38% in the CPX-351 arm and 26% in the 7+3 arm (P=0.036).
The rate of hematopoietic stem cell transplant was 34% in the CPX-351 arm and 25% in the 7+3 arm.
The median overall survival was 9.6 months in the CPX-351 arm and 5.9 months in the 7+3 arm (P=0.005).
All-cause 30-day mortality was 6% in the CPX-351 arm and 11% in the 7+3 arm. Sixty-day mortality was 14% and 21%, respectively.
Six percent of patients in both arms had a fatal adverse event (AE) on treatment or within 30 days of therapy that was not in the setting of progressive disease.
The rate of AEs that led to discontinuation was 18% in the CPX-351 arm and 13% in the 7+3 arm. AEs leading to discontinuation in the CPX-351 arm included prolonged cytopenias, infection, cardiotoxicity, respiratory failure, hemorrhage, renal insufficiency, colitis, and generalized medical deterioration.
The most common AEs (incidence ≥ 25%) in the CPX-351 arm 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.
The most common serious AEs (incidence ≥ 5%) in the CPX-351 arm were dyspnea, myocardial toxicity, sepsis, pneumonia, febrile neutropenia, bacteremia, and hemorrhage.
