Expert Insights: Phase III Clinical Trials in Non-Transfusion-Dependent (ENERGIZE) and Transfusion-Dependent (ENERGIZE-T) α- and β-Thalassaemia

Abstract

The thalassaemias are a heterogeneous group of inherited chronic blood disorders associated with impaired haemoglobin (Hb) synthesis, resulting in ineffective erythropoiesis, haemolysis, and the development of lifelong anaemia. The pathophysiology of thalassaemia is due, in part, to increased energy demand to clear globin aggregates and reactive O2 species, and maintain overall red blood cell (RBC) health, coupled with insufficient adenosine triphosphate (ATP) production. For this article, interviews were conducted by EMJ in December 2022 with two key opinion leaders. Kevin Kuo is a Clinician-Investigator and Staff Haematologist at the University Health Network, Toronto, Canada, and Associate Professor in the Division of Hematology, Department of Medicine, University of Toronto, Canada. Maria Cappellini is Professor of Medicine in the Department of Clinical Sciences and Community, University of Milan, Italy. Both haematologists have over 50 years of expertise and clinical experience between them in treating patients with thalassaemia. The two experts provided insights into two ongoing Phase III clinical trials for both α- and β-thalassaemia. These trials are investigating the effect of mitapivat, a first-in-class, small molecule pyruvate kinase activator, in patients across the full range of thalassaemia subtypes. The ENERGIZE trial is investigating mitapivat in patients with non–transfusion-dependent thalassaemia (NTDT), and the ENERGIZE-T trial is investigating mitapivat in patients with transfusion-dependent thalassaemia (TDT).