FDA Accepts New Drug Application for CPX-351 for AML

The FDA has accepted a new drug application (NDA) for CPX-351 – a liposomal formulation of cytarabine and daunorubicin encapsulated at a 5:1 molar ratio – for the treatment of acute myeloid leukemia (AML).

The NDA incorporates data from five clinical trials, including a controlled, pivotal, phase III trial that enrolled 309 patients (age range = 60-75 years) from 39 U.S. and Canadian sites. Patients were randomized to receive CPX-351 (100 μ/m2 on days 1, 3, and 5) or 7+3 (control arm; cytarabine 100 mg/m2 daily for 7 days followed by daunorubicin 60 mg/m2 on days 1, 2, and 3).

The results demonstrated that CPX-351 reduced the risk of death by 31 percent, compared with 7+3 in older adults with high-risk secondary AML. The median overall survival with CPX-351 was 9.56 months (95% CI 6.60-11.86), compared with 5.95 months (95% CI 4.99-7.75) with 7+3 (hazard ratio [HR] = 0.69; p=0.005).

Rates of grade 3-5 non-hematologic adverse events were similar between the CPX-351 and 7+3 cohorts, the most common of which were febrile neutropenia (68% vs. 71%), pneumonia (20% vs. 15%), hypoxia (13% vs. 15%), sepsis (9% vs. 7%), hypertension (10% vs. 5%), respiratory failure (7% each), fatigue (7% vs. 6%), bacteremia (10% vs. 2%), and decreased ejection fraction (5% each).

The FDA previously granted CPX-351 breakthrough-therapy designation for patients with therapy-related AML or AML with myelodysplasia-related changes. The FDA also granted CPX-351 fast track status for the treatment of older patients with secondary AML.

Source: Jazz Pharmaceuticals press release, May 31, 2017.