The European Medicines Agency has granted accelerated assessment to the marketing authorization application (MAA) for the FLT3 inhibitor quizartinib.
With this MAA, Daiichi Sankyo Company, Ltd., is seeking authorization for quizartinib to treat adults with FLT3-ITD-positive, relapsed or refractory acute myeloid leukemia (AML).
Accelerated assessment is given to products expected to be of major interest for public health and therapeutic innovation, and it can reduce the review timeline from 210 days to 150 days.
Quizartinib also has orphan drug designation from the European Commission.
The MAA for quizartinib is based on the phase 3 QuANTUM-R study. Results from this trial were presented at the 23rd Congress of the European Hematology Association in June.
QuANTUM-R enrolled adults with FLT3-ITD AML (at least 3% FLT3-ITD allelic ratio) who had refractory disease or had relapsed within 6 months of their first complete response (CR).
Patients were randomized to receive once-daily treatment with quizartinib (n=245) or a salvage chemotherapy regimen (n=122)—low-dose cytarabine (LoDAC, n=29); combination mitoxantrone, etoposide, and cytarabine (MEC, n=40); or combination fludarabine, cytarabine, and idarubicin (FLAG-IDA, n=53).
Patients who responded to treatment could proceed to hematopoietic stem cell transplant (HSCT), and those in the quizartinib arm could resume quizartinib after HSCT.
In all, 241 patients received quizartinib, and 94 received salvage chemotherapy—LoDAC (n=22), MEC (n=25), and FLAG-IDA (n=47). Of the 28 patients in the chemotherapy group who were not treated, most withdrew consent.
Thirty-two percent of quizartinib-treated patients and 12% of the chemotherapy group went on to HSCT.
The median follow-up was 23.5 months. The efficacy results include all randomized patients.
The overall response rate was 69% in the quizartinib arm and 30% in the chemotherapy arm.
The composite CR rate was 48% in the quizartinib arm and 27% in the chemotherapy arm. This includes:
- The CR rate (4% and 1%, respectively)
- The rate of CR with incomplete platelet recovery (4% and 0%, respectively)
- The rate of CR with incomplete hematologic recovery (40% and 26%, respectively).
The median event-free survival was 6.0 weeks in the quizartinib arm and 3.7 weeks in the chemotherapy arm (hazard ratio=0.90, P=0.1071).
The median overall survival was 6.2 months in the quizartinib arm and 4.7 months in the chemotherapy arm (hazard ratio=0.76, P=0.0177). The 1-year overall survival rate was 27% and 20%, respectively.
The safety results include only patients who received their assigned treatment.
Grade 3 or higher hematologic treatment-emergent adverse events occurring in at least 5% of patients (in the quizartinib and chemotherapy groups, respectively) included:
- Thrombocytopenia (35% and 34%)
- Anemia (30% and 29%)
- Neutropenia (32% and 25%)
- Febrile neutropenia (31% and 21%)
- Leukopenia (17% and 16%).
Grade 3 or higher non-hematologic treatment-emergent adverse events occurring in at least 5% of patients (in the quizartinib and chemotherapy groups, respectively) included:
- Sepsis/septic shock (16% and 18%)
- Hypokalemia (12% and 9%)
- Pneumonia (12% and 9%)
- Fatigue (8% and 1%)
- Dyspnea (5% for both)
- Hypophosphatemia (5% for both).