Avatrombopag in untreated severe aplastic anaemia - a Bayesian optimal phase 2 study

Abstract

Severe aplastic anaemia is a rare disease where current standard upfront treatment for patients ineligible for haematopoietic stem cell transplant (HSCT) is immunosuppressive therapy (IST). Although patients with severe AA treated with IST (horse antithymocyte globulin [ATG] and CyA) have overall responses reported in 50-75%, the minority achieve complete responses, approximately 20% are refractory to IST and approximately 30% will relapse by 2 years. Partial or no response to IST leaves patients at ongoing risk of life-threatening complications of AA such as infections, haemorrhage and patients will require ongoing supportive treatments such as antibiotics, red blood cell and platelet transfusions, to combat these complications. Eltrombopag is a thrombopoietin (TPO) mimetic and has shown promising efficacy for severe AA in phase II trials. Avatrombopag is a second generation TPO mimetic which has been studied in immune thrombocytopenia and thrombocytopenia due to chronic liver disease. It has several potential advantages over eltrombopag, including dosing, lack of toxicities, pharmacokinetics and potential increased potency. Avatrombopag has not been tested in AA to date. In this study, avatrombopag will be given in addition to standard IST to treatment naive severe AA patients to determine if the rate of production of platelets, red blood cells and white blood cells is increased.