The U.S. Food and Drug Administration has approved the hedgehog pathway inhibitor glasdegib (Daurismo) for use in combination with low-dose cytarabine (LDAC) to treat adults with newly diagnosed acute myeloid leukemia who are aged 75 years and older or who are ineligible for intensive chemotherapy.
The prescribing information for glasdegib includes a boxed warning detailing the risk of embryo-fetal death or severe birth defects associated with the drug.
The FDA’s approval of glasdegib is based on results from the phase 2 BRIGHT AML 1003 trial (NCT01546038). This trial included 111 adults with newly diagnosed AML and 14 patients with other conditions. The patients were randomized to receive glasdegib (at 100 mg daily) in combination with LDAC (n = 84) or LDAC alone (n = 41).
The complete response rate among the AML patients was 18.2% (14/77) in the glasdegib-LDAC arm and 2.6% (1/38) in the LDAC-only arm. The median overall survival was 8.3 months in the glasdegib-LDAC arm and 4.3 months in the LDAC-only arm (hazard ratio, 0.46; P = .0002).
The most common adverse events in the first 90 days of treatment, occurring in at least 30% of patients in either arm (glasdegib-LDAC and LDAC alone, respectively, were anemia (43% and 42%), fatigue (36% and 32%), hemorrhage (36% and 42%), febrile neutropenia (31% and 22%), musculoskeletal pain (30% and 17%), edema (30% and 20%), and thrombocytopenia (30% and 27%).
The incidence of serious adverse events was 79% in the glasdegib arm, and the most common events were febrile neutropenia (29%), pneumonia (23%), hemorrhage (12%), anemia (7%) and sepsis (7%).
Additional data from this trial are included in the prescribing information for glasdegib.
Glasdegib is a product of Pfizer.