A Multicenter, Open-Label, Single-Arm, Phase 2 Study To Evaluate The Efficacy And Safety Of Hetrombopag In Patients With Severe Aplastic Anemia (Saa)

Introduction: Severe aplastic anemia (SAA) is a hematologic disorder characterized by bone marrow hypoplasia and peripheral pancytopenia. Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine (CsA) is the standard first-line treatment for patients with SAA who are ineligible for hematopoietic stem cell transplantation (HSCT). For those refractory to or relapsed after IST, eltrombopag (an oral thrombopoietin receptor agonist) were recommended as the second-line therapy by US FDA and European Medicines Agency (EMA). However, in several countries including China, eltrombopag has not been approved for use in patients with SAA, so there is an urgent unmet medical need for additional efficient treatment options. Hetrombopag, another oral thrombopoietin receptor agonist, has similar mechanism in stimulating thrombopoietin receptor signaling pathway as eltrombopag and better pharmacological performance than eltrombopag in pre-clinical study (Xie et al, JCMM 2018). In a phase 1 trial, hetrombopag was safe and well-tolerated in healthy subjects with potent thrombopoietic activity and acceptable pharmacokinetic profiles (Zheng et al, BCPT 2017). Here, in this phase 2 trial (NCT03557099), we aimed to assess the activity and safety of hetrombopag in patients with SAA who have had an insufficient response to IST.