Pyruvate kinase deficiency (PKD) is a rare autosomal recessive disorder caused by mutations in PKLR leading to chronic haemolytic anaemia of variable severity, from fully-compensated to life-threatening, transfusion dependent anemia.
The only curative treatment for PKD nowadays is allogenic stem cell transplantation, but this carries a considerable risk of mortality, especially from unrelated donors. Accordingly, contra-indications and adverse effects should be considered in each patient. Nevertheless, other curative options as gene therapy or disease target drugs are currently under clinical trial phases.
A recent phase 2 study has evaluated the safety and efficacy of mitapivat, an oral small-molecule allosteric activator of pyruvate kinase in red cells, in 52 adults with PKD. The administration of mitapivat was associated with a rapid increase in the hemoglobin level in 50% of adults with PKD, with a sustained response during a median follow-up of 29 months during the extension phase.
The paper “Safety and Efficacy of Mitapivat in Pyruvate Kinase Deficiency” has just been published in the New England Journal of Medicine with the participation of the EuroBloodNet experts Frédéric Galactéros, Wilma Barcellini, and Eduard J. van Beers.