EC Grants EU‑Wide Approval for PYRUKYND in Thalassemia

The European Commission approved Agios Pharmaceuticals’ PYRUKYND® (mitapivat) for adults with anemia associated with transfusion-dependent and non-transfusion-dependent alpha- or beta-thalassemia, making it the first therapy authorized across all EU member states for this broad patient population.

The decision expands mitapivat’s reach beyond pyruvate kinase deficiency and marks another major regulatory milestone for the oral pyruvate kinase activator. PYRUKYND already holds approvals for thalassemia in the United States, Saudi Arabia, and the United Arab Emirates. Agios will commercialize the therapy in Europe through its partnership with Avanzanite Bioscience.

Phase 3 Trials Supported Approval

The approval was based on data from the global Phase 3 ENERGIZE (NCT04770753) and ENERGIZE-T (NCT04770779) studies evaluating mitapivat in adults with alpha- or beta-thalassemia.

In the ENERGIZE trial, 194 adults with non-transfusion-dependent disease were randomized 2:1 to receive mitapivat 100 mg twice daily or placebo. The study met its primary endpoint of hemoglobin response, defined as at least a 1.0 g/dL increase in average hemoglobin levels between Weeks 12 and 24.

The companion ENERGIZE-T trial enrolled 258 transfusion-dependent patients and achieved its primary endpoint of transfusion reduction response through Week 48, defined as at least a 50% reduction in transfused red blood cell units alongside a reduction of at least two units during any consecutive 12-week interval.

Both studies also evaluated fatigue, transfusion independence, safety, and tolerability. Mitapivat demonstrated a generally consistent and manageable safety profile across study populations.

The findings support mitapivat as a potential oral treatment option for patients who remain dependent on transfusions or continue to experience symptomatic anemia despite supportive care.

Addressing a Major Unmet Need in Thalassemia

Thalassemia is a rare inherited blood disorder caused by impaired hemoglobin production, leading to chronic anemia, fatigue, organ complications, and reduced life expectancy. Many patients require lifelong transfusions and iron chelation therapy, while treatment options remain limited, particularly for non-transfusion-dependent disease.

Mitapivat activates pyruvate kinase in red blood cells, improving cellular energy production and enhancing red cell survival. By improving red cell metabolism, the therapy targets ineffective erythropoiesis and chronic hemolytic anemia that drive disease burden in thalassemia.

Experts Highlight Clinical Significance

Maria Domenica Cappellini, MD, Professor of Internal Medicine at the University of Milan and an investigator in the Phase 3 program, said the approval addresses a major unmet need in thalassemia and highlighted PYRUKYND’s potential to improve outcomes regardless of genotype or transfusion status.

Agios CEO Brian Goff said the EU authorization reinforces the company’s growing presence in rare hematologic diseases and supports broader global adoption of mitapivat. Following the approval, Agios and Avanzanite plan to advance commercial rollout efforts across Europe.

Reference

Agios’ PYRUKYND® (mitapivat) Approved in the European Union for Adults with Thalassemia – Agios Pharmaceuticals, Inc.

Study Details | NCT04770753 | A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-NTDT) | ClinicalTrials.gov

Study Details | NCT04770779 | A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-TDT) | ClinicalTrials.gov