In November 2016, the European Medicines Agency’s (EMAs) Committee for Orphan Medicinal Products (COMP) granted Orphan Drug Designation for crenolanib for the treatment of Acute Myeloid Leukemia (AML).
FMS like Tyrosine Kinase 3 (FLT3) mutations with Internal Tandem Duplications (ITD) occurs in approximately 30% of AML patients. These mutations often lead to poor prognosis and disease relapse in AML patients (Zimmerman et al., 2013).
Crenolanib is a novel Tyrosine Kinase Inhibitor (TKI) that was initially developed as a selective and potent inhibitor for Platelet-Derived Growth Factor Receptor (PDGFR) α and β but it also has a high affinity for FLT3 (Zimmerman et al., 2013). Crenolanib binds to and inhibits both wild-type and mutated forms of FLT3, which can lead to the inhibition of FLT3-related signal transduction pathways.
Crenolanib is currently being explored in multiple trials for newly diagnosed (NCT02283177) and relapsed/refractory (NCT02298166, NCT02400281, NCT01657682) AML patients with or without FLT3 mutations.