Agios Pharmaceuticals’ Oral Mitapivat Increases Hemoglobin Levels and Improves Markers of Erythropoiesis in Patients with Non-Transfusion-Dependent Thalassemia

December 7, 2020 – Agios Pharmaceuticals reported preliminary findings from their Phase 2 study of mitapivat in non-transfusion-dependent thalassemia at the 2020 American Society of Hematology (ASH) virtual medical conference. Mitapivat activates the pyruvate kinase-R (PKR) enzyme, which improves red blood cell energy metabolism. Mitapivat was shown to improve ineffective erythropoiesis and anemia in a mouse model of thalassemia. This is the first clinical trial to evaluate PKR activation as a therapeutic option for α- and β-thalassemia, and it is the first clinical trial aimed at treating α-thalassemia.

A preliminary analysis was performed on data collected from the first 13 patients enrolled in the Phase 2 study of mitapivat in adult patients with non-transfusion-dependent α- and β-thalassemia. This showed that mitapivat treatment resulted in a ≥1.0 g/dL increase in Hemoglobin levels in all 4 (100%) α-thalassemia patients and in 8 out of 9 (88.9%) patients with β-thalassemia who completed 12 weeks of treatment. The mean increase in Hemoglobin levels across all 13 patients was 1.34 g/dL from weeks 4-12. Improvements in markers of hemolysis and erythropoiesis were also observed, which were consistent with the increase in Hemoglobin levels.

Nine patients with non-transfusion-dependent β-thalassemia had completed 24 weeks of treatment at the time of data analysis. In this group, the mean increase in Hemoglobin levels from weeks 4–24 was 1.43 g/dL.

Patients were considered non-transfusion-dependent and eligible to enroll in this study if they received no more than 5 units of red blood cells during the 24-week period leading up to the first day of study drug, and no red blood cell transfusions in the 8 weeks leading up to the first day of study drug. Diagnoses which were eligible to enroll in this study, provided that they met the criteria for non-transfusion-dependence, included: β-thalassemia intermedia, Hb E β-thalassemia, α-thalassemia (Hb H disease), or β-thalassemia with mutations of 1 or more α genes.

Mitapivat is taken orally twice per day. Mitapivat was well tolerated with no serious adverse events and no adverse events leading to treatment discontinuation at the time of data cutoff.

The Phase 2 study of mitapivat in non-transfusion-dependent alpha- and beta-thalassemia has been fully enrolled. Further information about the preliminary Phase 2 findings can be found in the ASH meeting abstract at: https://ash.confex.com/ash/2020/webprogram/Paper136662.html


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