Orphan Drug Designation granted for gilteritinib in Japan for the treatment of FLT3 mutated AML

On 22 March 2018, Japan’s Ministry of Health, Labor, and Welfare (MHLW)  granted Orphan Drug Designation to gilteritinib, a fms like tyrosine kinase 3 (FLT3) inhibitor, for the treatment of patients with FLT3 mutated acute myeloid leukemia (AML).¹ This comes after gilteritinib was granted Orphan Drug Designation by the European Medicines Agency’s (EMA)  Committee for Orphan Medicinal Products (COMP) in January 2018. Gilteritinib has also be been granted Orphan Drug Designation and Fast Track Designation by the U.S. Food and Drug Administration (FDA).

Gilteritinib is a potent, oral FLT3/AXL inhibitor, which binds to and inhibits both the wild-type and mutated forms of FLT3. Findings from a phase I/II dose escalation study (NCT02421939), which was published in Lancet Oncology (as reported by the AGP) revealed that gilteritinib monotherapy was well tolerated and generated frequent, prolonged, clinically important responses in FLT3 mutated patients with R/R AML.² 

Additionally, data from an ongoing phase I dose-escalation study  (NCT02236013), presented at the 59th American Society of Hematology (ASH) Annual Meeting by Keith Pratz, MD, from the John Hopkins University, demonstrated that gilteritinib in combination with intensive chemotherapy was “well tolerated” with a maximum tolerated dose at ≥ 120 mg/day in patients with newly diagnosed AML. A higher response for this combination regimen was seen in FLT3^mut+ AML patients.³ In an interview with the AGP, Keith Pratz highlighted that the responses observed in patients treated in this phase I dose escalation trial has been “good so far”.

Currently, gilteritinib is being investigated in multiple studies including the phase III ADMIRAL study (NCT02421939) which is assessing oral gilteritinib 120 mg/day in R/R AML patients with FLT3 mutations after first-line therapy. The AGP spoke to Alexander E. Perl from the Abramson Comprehensive Cancer Center, University of Pennsylvania, about the design and plan of the phase III ADMIRAL study.