Agios Pharmaceuticals presented new data from the ongoing long-term extension of a Phase 2 open-label study of mitapivat (PYRUKYND®) in adults with non-transfusion dependent α- or β-thalassemia at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition. The data showed sustained improvements in hemoglobin concentration and reduced markers of hemolysis and ineffective erythropoiesis for up to 72 weeks of treatment.
Durable Improvements with Mitapivat
The study results demonstrated that mitapivat, a first-in-class, oral, small molecule allosteric activator of wild-type and mutated pyruvate kinase (PK) enzymes, led to durable improvements in hematological parameters. Specifically, the improvements in hemoglobin concentration and markers of hemolysis were observed in both α- and β-thalassemia patients. Furthermore, markers of iron homeostasis remained stable or improved through Week 72. The safety profile of mitapivat remained consistent with previous studies, indicating good tolerability.
Expert Commentary
"The data presented today continue to underscore the potential of PK activation to address multiple aspects of the complex underlying pathophysiology of α- and β-thalassemia, including hallmarks of the disease: hemolysis and ineffective erythropoiesis," said Dr. Kevin Kuo, hematologist at University of Toronto, Toronto General Hospital, and an investigator in the study. He also noted the lack of approved treatment options for α-thalassemia and the limited options for β-thalassemia, emphasizing the potential clinical benefits of mitapivat for a broad spectrum of hemolytic anemias.
Burden of Thalassemia
In addition to the mitapivat data, Agios presented findings from a systematic literature review investigating the clinical, health-related quality of life, and economic burden associated with α-thalassemia. The review highlighted significant clinical complications in adult patients, including moderate-to-severe iron overload (31%), iron overload of unspecified severity (66%), and advanced liver fibrosis (20%), with complications being more pronounced in non-deletional α-thalassemia. The review underscored the need for further research to fully characterize the burden of disease.
Ongoing Clinical Trials
Agios is currently focusing on enrolling patients in two global, placebo-controlled pivotal trials – ENERGIZE and ENERGIZE-T – to evaluate mitapivat in adults with non-transfusion dependent and transfusion dependent thalassemia, respectively. The company anticipates enrolling a substantial portion of patients in these trials by the end of the year.
Thalassemia Overview
Thalassemia is an inherited blood disorder caused by mutations in α- or β-globin genes, leading to excessive red blood cell destruction. This results in hemolytic anemia, ineffective erythropoiesis, and iron overload. Thalassemia is associated with serious complications, including fatigue, jaundice, facial bone deformities, and reduced life expectancy. Current management strategies for β-thalassemia include red blood cell transfusions, splenectomy, and stem cell transplant, each carrying short- and long-term risks. Currently, there are no approved therapies for α-thalassemia.
