FDA Approves Glasdegib for AML in Adults Age 75 or Older or Who Have Comorbidities

Approval of a hedgehog pathway inhibitor is based on results from the BRIGHT AML 1003 study

On 21 November 2018, the US Food and Drug Administration (FDA) approved glasdegib (DAURISMO, Pfizer Labs) in combination with low-dose cytarabine (LDAC), for newly-diagnosed acute myeloid leukaemia (AML) in patients who are 75 years old or older or who have comorbidities that preclude intensive induction chemotherapy. 

Approval was based on a multicentre, open-label, randomised study (BRIGHT AML 1003, NCT01546038) that included 115 patients with newly-diagnosed AML who met at least one of the following criteria: a) age 75 years or older, b) severe cardiac disease, c) baseline Eastern Cooperative Oncology Group performance status of 2, or d) baseline serum creatinine >1.3 mg/dL. 

Patients were randomised 2:1 to receive glasdegib, 100 mg daily, with LDAC 20 mg subcutaneously twice daily on days 1 to 10 of a 28-day cycle (N = 77) or LDAC alone (N = 38) in 28-day cycles until disease progression or unacceptable toxicity. 

Efficacy was established based on an improvement in overall survival (date of randomisation to death from any cause).  With a median follow-up of 20 months, median survival was 8.3 months (95% CI: 4.4, 12.2) for the glasdegib plus LDAC arm and 4.3 months (95% CI: 1.9, 5.7) for the LDAC alone arm and HR of 0.46 (95% CI: 0.30, 0.71; p = 0.0002). 

The most common adverse reactions occurring in ≥ 20% of patients were anaemia, fatigue, haemorrhage, febrile neutropenia, musculoskeletal pain, nausea, oedema, thrombocytopenia, dyspnoea, decreased appetite, dysgeusia, mucositis, constipation, and rash. 

The recommended glasdegib dose is 100 mg orally, once daily. DAURISMO has not been studied in patients with the comorbidities of severe renal impairment or moderate-to-severe hepatic impairment. 

Full prescribing information for DAURISMO is available here.

FDA granted this application priority review and orphan product designation. 

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.