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The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for CPX-351 (Vyxeos), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle, to treat adults with therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes.
The FDA’s breakthrough therapy designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.
To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
Phase 3 trial
The breakthrough designation for CPX-351 is primarily based on positive results from a phase 3 trial in older patients with previously untreated, high-risk, secondary AML.
The trial was sponsored by Celator Pharmaceuticals, Inc., the company developing CPX-351.
The company has released some results from the trial, and additional data are scheduled to be presented at the 2016 ASCO Annual Meeting (abstract 7000).
The trial enrolled 309 patients, ages 60 to 75, with one of the following:
- Untreated AML and a history of prior cytotoxic treatment
- Antecedent myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia, with or without prior hypomethylating therapy
- AML with WHO-defined, MDS-related cytogenetic abnormalities.
One hundred and fifty-three patients were randomized to receive CPX-351, and 156 were randomized to 7+3 (cytarabine continuously for 7 days and a single dose of daunorubicin for the first 3 days).
The treatment arms were well-balanced for sex, race, age, performance status, AML subtype, MDS-related cytogenetics, and prior hypomethylating therapy.
The trial met its primary endpoint, demonstrating a significant improvement in overall survival with CPX-351. The median overall survival was 9.56 months in the CPX-351 arm and 5.95 months in the 7+3 arm. The hazard ratio was 0.69 (P=0.005).
According to researchers, there was no substantial difference between the treatment arms with regard to grade 3-5 adverse events.
About CPX-351
CPX-351 is a liposomal formulation of a 5:1 molar ratio of cytarabine and daunorubicin.
In one phase 2 trial, CPX-351 conferred a significant improvement in survival—over investigator’s choice of therapy—when used as salvage therapy in poor-risk patients with AML.
In another phase 2 trial, CPX-351 conferred a significant survival benefit—over 7+3—in patients with secondary AML.
The FDA previously granted CPX-351 fast track designation to treat elderly patients with secondary AML. The agency established the fast track designation process to expedite the review of drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs.
The designation allows a drug’s developer to submit sections of a new drug application (NDA) on a rolling basis, so the FDA can review portions of the NDA as they are received instead of waiting for the entire NDA submission. A fast-track-designated product could be eligible for priority review if supported by clinical data at the time of NDA submission.
