Pyrukynd (mitapivat) Receives Positive CHMP Opinion for Adults with Thalassemia – Agios Pharmaceuticals

Agios Pharmaceuticals Inc. announced that the Committee for Medicinal Products for Human Use (CHMP) of the EMA has adopted a positive opinion for the new indication for Pyrukynd  (mitapivat), an oral pyruvate kinase (PK) activator, in adults for the treatment of anemia associated with transfusion-dependent and non-transfusion-dependent alpha- or beta-thalassemia. The CHMP’s opinion is based on the results from the global, randomized, double-blind, placebo-controlled ENERGIZE-T and ENERGIZE Phase III trials in adults with transfusion-dependent and non-transfusion-dependent alpha- or beta-thalassemia, respectively. The European Commission will now review the CHMP’s opinion, with the final decision expected by early 2026.

ENERGIZE (NCT04770753) and ENERGIZE-T (NCT04770779) are global, randomized, double-blind, placebo-controlled Phase III trials evaluating the efficacy and safety of mitapivat in adults with alpha- or beta-thalassemia.

The ENERGIZE trial randomized 194 non-transfusion-dependent patients 2:1 to receive either mitapivat 100 mg twice daily or placebo. The primary endpoint was the proportion of patients achieving a hemoglobin response, defined as an increase of ≥1.0 g/dL in average hemoglobin concentrations from week 12  to week 24 compared with baseline. Key secondary endpoints included changes from baseline in Functional Assessment of Chronic Illness Therapy‐Fatigue (FACIT-Fatigue) scores and in average hemoglobin concentration from week 12 to week 24. The study also assessed safety and tolerability.

The ENERGIZE-T trial randomized 258 transfusion-dependent patients 2:1 to receive either mitapivat 100 mg twice daily or placebo. The primary endpoint was the proportion of patients achieving a transfusion reduction response (TRR), defined as a ≥50% reduction in transfused red blood cell (RBC) units with a reduction of ≥2 units of transfused RBCs in any continuous 12-week period through week 48. Several additional transfusion reduction measures were included as key secondary endpoints, and achievement of transfusion independence was a secondary endpoint. The study also assessed safety and tolerability.

“The CHMP’s positive opinion marks an important step forward for the thalassemia community in Europe,” said Dr.  Sarah Gheuens, Chief Medical Officer and Head of R&D, Agios. “Thalassemia is a debilitating disease that places a profound burden on patients and families, with few, if any, therapeutic options currently available to help manage the condition. PYRUKYND represents a promising new medicine to address this urgent need, and we look forward to the potential of bringing it to patients across Europe.”