CPX-351, whose proposed brand name is Vyxeos, is an investigational treatment for acute myeloid leukemia (AML), a rapidly progressing blood cancer, that consists of a combination of the chemotherapy drugs cytarabine and daunorubicin encapsulated in a tiny liposome. A new drug application (NDA) seeking approval for CPX-351 was recently filed by Jazz Pharmaceuticals and accepted by the Food and Drug Administration (FDA) with priority review status.

How CPX-351 works

CPX-351 uses CombiPlex technology, which encapsulates drugs at a fixed molar ratio (5:1 for CPX-351) in a nano-scale delivery vehicle such as liposomes or nanoparticles. In contrast to the current “seven plus three” regimen for these chemotherapies — seven days of cytarabine and three days of daunorubicin — CPX-351 is taken up by tumor cells intact, and then cytarabine and daunorubicin are released within the cell at their synergistic ratio. The drugs’ encapsulation is designed to maintain these optimized ratios, reduce degradation, and minimize the drugs’ systematic impact, or its effects on non-cancerous cells. Prolonged exposure of CPX-351 in the bone marrow and sustained delivery of its cytotoxic therapies are reported to better ensure the death of tumor cells.

CPX-351 in clinical trials

In a randomized, open-label, Phase 2 clinical trial (NCT00788892), CPX-351 (100 U/m2, equivalent to 100 mg/m2 cytarabine and 44 mg/m2 daunorubicin) was compared with the seven plus three regimen (100 mg/m2 cytarabine and 60 mg/m2 daunorubicin) as an induction therapy (an initial or first-round treatment). The trial enrolled 126 AML patients, ages 60 to 75. The results showed an improved response with prolonged event-free survival and overall survival, especially in patients with secondary AML (typically, AML caused by chemo or radiation treatment for a previous cancer).

In a separate Phase 2, randomized and open-label study (NCT00822094), 125 AML patients with a first relapse, ages of 18 to 65, were assigned CPX-351 or investigators’ choice of chemotherapy. Results showed a slightly higher response among AML relapse patients in the CPX-351-treated group.

The FDA place CPX-351 on fast track development as a possible treatment of elderly patients with secondary AML in January 2015, based on the results of the two Phase 2 studies. CPX-351 was also granted orphan drug designation by the FDA and the European Commission for the treatment of AML.

Since the drug has shown efficacy (complete response) and better tolerance at doses of 50 U/m2 and 75 U/m2 (below the maximum tolerated dose of 100 U/m2) in Phase 1 and Phase 2 studies, a randomized and open-label Phase 2 clinical study (NCT02286726) is comparing outcomes of newly diagnosed AML patients — all thought unlikely to support an induction therapy — at these lower doses. Results so far found that the two CPX-351 dose levels are safe and show clinical benefit in these AML patients. Since there seems to be equal or better clinical benefit with 75 U/m2 without an increased mortality risk, the maximum tolerated dose of 100 U/m2 will now be tested in a third group. This single-site study, taking place at MD Anderson Cancer Center in Texas, is currently recruiting patients.

The NDA submission included clinical data from five studies, including a randomized Phase 3 trial (NCT01696084) comparing CPX-351 (100 U/m2) with a seven plus three regimen of cytarabine (100 mg/m2) and daunorubicin (60 mg/m2) in elderly patients (ages 60 to 75) with high-risk secondary AML. The trial included 309 patients across 39 sites throughout both the U.S. and Canada. The results showed that CPX-351 treatment significantly improved overall survival, event-free survival, and response without an increase in 60-day mortality or in the frequency or severity of adverse events.

Based on these results, CPX-351 was designed a breakthrough therapy by the FDA in May 2016 for the treatment of adults with secondary AML. The designation helps to speed the therapy’s development and review process.


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