Mitapivat (Pyrukynd®), an oral, allosteric activator of pyruvate kinase (PK), is approved in the USA for the treatment of haemolytic anaemia in adults with PK deficiency and in the EU and UK for the treatment of PK deficiency in adults. Mitapivat acts by restoring activity of the red blood cell (RBC) PK enzyme, which is dysfunctional due to genetic mutations in the PKLR gene in patients with PK deficiency. In the double-blind placebo-controlled phase III ACTIVATE trial in adults with PK deficiency who were not regularly RBC transfused, mitapivat was superior to placebo in improving haemoglobin levels. In the single-arm phase III ACTIVATE-T trial in adults with PK deficiency who were regularly RBC transfused, a reduction in RBC transfusion burden was observed with mitapivat. In both trials, mitapivat improved other clinical parameters of haemolysis and patient-reported health-related quality of life. At the approved twice-daily dosage range, mitapivat was generally well tolerated, with adverse events generally being mild to moderate in severity. Results from an ongoing extension study in previously enrolled phase III trial patients will be of interest. Currently available data indicate that mitapivat, the first approved disease-modifying drug for PK deficiency in adults, is a valuable treatment option for this rare disease.
Pyruvate kinase (PK) deficiency is a rare hereditary disease caused by mutations affecting the function of the PK enzyme in red blood cells (RBCs) and is characterized by chronic haemolytic anaemia. Treatment options for adults with PK deficiency have historically been limited to supportive care and are themselves associated with potentially serious complications. Oral mitapivat (Pyrukynd®) is the first disease-modifying drug to be approved for use in adults with PK deficiency and acts by restoring activity of the dysfunctional RBC PK enzyme. Based on findings from two phase III clinical trials, twice-daily oral mitapivat provided clinical benefit in adults with PK deficiency, both in patients not requiring, and requiring, regular RBC transfusions. Improvements in disease-specific health-related quality of life were observed in adults with PK deficiency treated with mitapivat. Mitapivat was generally well tolerated, with most adverse events being mild to moderate in severity. In conclusion, current evidence indicates that mitapivat is a valuable treatment option for adults with PK deficiency.
© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.