Unmet needs in β-thalassemia and the evolving treatment landscape

Abstract

β-thalassemias are genetic disorders causing an imbalance in hemoglobin production, leading to varying degrees of anemia, with two clinical phenotypes: transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). Red blood cell transfusions and iron chelation therapy are the conventional treatment options for the management of β-thalassemia. Currently available conventional therapies in thalassemia have many challenges and limitations. Accordingly, multiple novel therapeutic approaches are currently being developed for the treatment of β-thalassemias. These strategies can be classified into three categories based on their efforts to address different aspects of the underlying pathophysiology of β-thalassemia: correction of the α/β globin chain imbalance, addressing ineffective erythropoiesis, and targeting iron dysregulation. Managing β- thalassemia presents challenges due to the many complications that can manifest, limited access and availability of blood products, and lack of compliance/adherence to treatment. Novel therapies targeting ineffective erythropoiesis and thus improving anemia and reducing the need for chronic blood transfusions seem promising. However, the complex nature of the disease itself requires personalized treatment plans for each patient. Collaborations and partnerships between thalassemia centers can also help share knowledge and resources, particularly in regions with higher prevalence and limited resources. This review will explore the different conventional treatment modalities available today for the management of β-thalassemia, discuss the unmet needs and challenges associated with them in addition to exploring the role of some novel therapeutic agents in the field.

Keywords: Blood transfusion; Challenges; Iron chelation therapy; Novel therapies; Unmet needs; β-thalassemia.