On 21st August 2017, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to SY-1425 (tamibarotene) for the treatment of patients with Acute Myeloid Leukemia (AML).1
Highly specialized regions known as super-enhancers, associated with selective Retinoic Acid Receptor Alpha (RARα) and Monocyte Specific Factor (IRF8) genes, have been identified in blast cells of some patients with AML. These super-enhancers have been shown to drive high expression of RARα and IRF8, thus driving AML blasts to be in an immature, undifferentiated, and proliferative state. SY-1425 is an oral, first-in-class, selective RARα agonist. SY-1425 binds to RARα, which leads to reactivation of differentiation and prolongation of survival in preclinical models of AML with high RARα expression.2
Currently, SY-1425 is being evaluated in a biomarker directed phase II study (NCT02807558) aiming to assess its safety and efficacy alone or in combination with azacitidine in newly diagnosed or relapsed/refractory AML patients who are positive for either RARα or IRF8. The primary endpoint of the study is Overall Response Rate (ORR).