Agios secures Euro approval for Pyrukynd in thalassemia

Edited by Robert McTiernan··2 min read

Agios Pharmaceuticals (Nasdaq: AGIO) has received European Commission marketing authorization for Pyrukynd (mitapivat) in adults with anemia associated with transfusion-dependent and non-transfusion-dependent alpha- or beta-thalassemia, making it the only medicine approved across all EU member states for this broad patient population. The approval, which carries orphan medicinal product designation, extends mitapivat’s regulatory footprint to four markets — the US, Saudi Arabia, the United Arab Emirates, and now the EU.

The EC authorization covers both transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT), and applies to both alpha- and beta-thalassemia genotypes. Mitapivat is administered orally at 100 mg twice daily. Avanzanite Bioscience B.V., a specialty pharmaceutical company headquartered in Amsterdam, holds an exclusive agreement with Agios for commercialization and distribution of Pyrukynd across the European Economic Area, the United Kingdom, and Switzerland. In the US, mitapivat is marketed under the brand name Aqvesme for the thalassemia indication and as Pyrukynd for pyruvate kinase (PK) deficiency.

Mitapivat is an oral small-molecule allosteric activator of erythrocyte pyruvate kinase (PKR), the red blood cell isoform encoded by PKLR. By stabilizing the active conformation of PKR, the drug increases enzymatic activity at the terminal step of glycolysis, raising ATP levels in red blood cells and reducing hemolysis — a mechanism relevant across thalassemia genotypes regardless of transfusion status.

Clinical evidence from the ENERGIZE program

The EC decision is based on data from two global, randomized, double-blind, placebo-controlled Phase III trials: ENERGIZE (NCT04770753) in NTDT and ENERGIZE-T (NCT04770779) in TDT.

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ENERGIZE enrolled 194 adults with non-transfusion-dependent alpha- or beta-thalassemia, randomized 2:1 to mitapivat 100 mg twice daily or placebo. The primary endpoint was hemoglobin response, defined as an increase of at least 1.0 g/dL in average hemoglobin concentration from Week 12 through Week 24 compared with baseline. ENERGIZE-T enrolled 258 adults with transfusion-dependent disease under the same randomization scheme, with a primary endpoint of transfusion reduction response — defined as a 50% or greater reduction in transfused red blood cell units with a reduction of at least two units in any consecutive 12-week period through Week 48. Both trials included open-label extension periods.

Competitive context

Pyrukynd enters a thalassemia treatment landscape that includes luspatercept (Reblozyl, Bristol Myers Squibb), an erythroid maturation agent approved for transfusion-dependent beta-thalassemia in both the US and EU, and betibeglogene autotemcel (Zynteglo, bluebird bio), a one-time lentiviral gene therapy approved in the US for transfusion-dependent beta-thalassemia. Mitapivat’s oral chronic dosing profile and coverage of both alpha- and beta-thalassemia across transfusion strata distinguishes it from these options, though direct comparative data are not available. Luspatercept is also in late-stage development for alpha-thalassemia, which would extend its overlap with mitapivat’s approved scope.

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