PF 04449913 filed and given priority review by FDA in acute myeloid leukemia.- Pfizer.

Pfizer announced that the FDA accepted the company�s New Drug Application and granted Priority Review designation for PF 04449913 (glasdegib), an investigational oral smoothened (SMO) inhibitor, being evaluated for the treatment of adult patients with previously untreated acute myeloid leukemia (AML) in combination with low-dose cytarabine (LDAC), a type of chemotherapy. The FDA grants Priority Review designation to medicines that may offer significant advances in treatment or may provide a treatment where no adequate therapy exists. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is in December 2018.

The submission is based on results from the Phase II BRIGHT 1003 study, a randomized, open-label, multicenter trial investigating glasdegib combined with LDAC (n=88) versus LDAC alone (n=44) in 132 patients with previously untreated AML or high-risk myelodysplastic syndrome (MDS) who were not eligible for intensive chemotherapy. Results demonstrated a significant improvement in the primary endpoint of overall survival (OS). Median OS was 8.8 months for patients treated with glasdegib plus LDAC compared with 4.9 months for patients treated with LDAC only. This difference represented a 49.9 percent reduction in the risk of death for patients treated with glasdegib plus LDAC (HR: 0.501, 95% CI: 0.334, 0.752, one-sided p-value 0.0003). The BRIGHT 1003 results were presented in 2016 at the 58th American Society of Hematology Annual Meeting.

The most frequently (at least 30% of patients) reported adverse events (AEs) in patients treated with glasdegib plus LDAC compared to LDAC alone were anemia (45% vs 42%), febrile neutropenia (36% vs 27%), nausea (36% vs 12%), decreased appetite (32% vs 12%), fatigue (31% vs 20%) and thrombocytopenia (30% vs 27%). The most frequently (at least 15% of patients) reported serious AEs for patients treated with glasdegib plus LDAC compared to LDAC alone were febrile neutropenia (29% vs 20%) and pneumonia (21% vs 17%).