FDA Grants Priority Review to Glasdegib for Acute Myeloid Leukemia

The FDA granted a priority review to a new drug application (NDA) for glasdegib, an investigational oral smoothened (SMO) inhibitor, for the treatment of adult patients with previously untreated acute myeloid leukemia (AML) in combination with low-dose cytarabine (LDAC), a type of chemotherapy.

“Patients with acute myeloid leukemia who are ineligible for intensive chemotherapy are in critical need of new treatment options to improve their overall survival,” Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development, said in a statement. “Glasdegib is the first smoothened inhibitor to potentially offer such a benefit to patients with acute myeloid leukemia, and we are proud that our application was accepted by the FDA for Priority Review.”

Glasdegib—a once-daily therapy that is thought to inhibit the SMO receptor and disrupt the Hedgehog pathway, which regulates fundamental processes in embryonic development including stem cell maintenance, cell differentiation, tissue polarity, and cell proliferation—has not received regulatory approval in any country.¹

BRIGHT 1003 Study

The agency based its decision on results from the randomized, open-label, multicenter phase 2 BRIGHT 1003 study—designed to compared 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.

Overall survival (OS) served as the primary endpoint. Those treated with the combination demonstrated a superior median OS (8.8 months vs. 4.9 months) compared with patients who received LDAC only, which represented a 49.9% reduction in the risk of death for the combination arm (hazard ratio (HR) = 0.50; 95% CI, 0.33-0.75; P = .0003).

The most frequent adverse events (AEs) in the combination arm compared with the control arm included 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 frequent serious AEs were febrile neutropenia (29% vs. 20%) and pneumonia (21% vs. 17%).

The FDA set the Prescription Drug User Fee Act (PDUFA) goal date for December 2018.

Reference

Gupta S, Takebe N, LoRusso P. Targeting the Hedgehog pathway in cancer. Ther Adv Med Oncol. 2010 Jul; 2(4): 237—250.doi: 10.1177/1758834010366430