Current and Future Treatments of Iron Overload in Thalassemia Patients

Iron overload is a major complication among thalassemia patients. In these patients, ineffective erythropoiesis decreases hepcidin production resulting in iron dysregulation, which leads to a number of serious complications. Damage to organs susceptible to iron overload could be prevented by effective iron chelation. Despite the efficacy of iron chelators, limitations to their use are that they are only used after the patients have suffered from iron overload, and they have also been associated with a number of side effects. New therapeutic strategies for the treatment of thalassemia have focused on addressing the pathophysiology of the disease. Drugs currently being developed to improve ineffective erythropoiesis are aimed at increasing hemoglobin levels and subsequently decreasing iron absorption. The new therapeutic drugs in this class include pegylated erythropoietin, JAK 2 inhibitors, and TGF-β activin receptor traps (sotatercept and luspatercept). Luspatercept is currently recognized as the most promising drug in this class and has completed phase III of trials. With the aim of improving iron dysregulation, these new therapeutic strategies focus on preventing the absorption of iron in the gastrointestinal tract. These therapies involve hepcidin agonists and specific derivatives, such as LJPC-401 and Rusfertide (formerly PTG- 300), certain ferroportin inhibitors, such as Vamifeport (formerly VIT-2763) and transmembrane protease serine 6 (TMPRSS6) antisense oligonucleotides. Although the therapeutic potential of these new treatments in thalassemia patients is promising, ongoing clinical trials are needed. Importantly, these new treatment strategies may provide a new, more effective paradigm of treatment in thalassemia patients.