Pyruvate kinase deficiency (PKD), a rare autosomal recessive disease, often leads to chronic hemolytic complications stemming from mutations in the PKLR gene. Mitapivat, an innovative, allosteric activator of the pyruvate kinase enzyme in red blood cells, has emerged as a potential therapeutic agent. This systematic review aims to meticulously evaluate the efficacy and safety of Mitapivat in treating PKD patients.

We conducted a comprehensive search across three major databases—PubMed, Web of Science, and Scopus—up to November 2023, utilizing a single-arm meta-analysis methodology.

Our analysis included three clinical trials comprising 94 PKD patients. Hemoglobin (HB) levels improved, with an average increase of 1.05 g/dl (95% Confidence Interval [CI]: -0.22 to 2.33). In terms of hemolysis indicators, there was a notable decrease in indirect bilirubin (mean change: -1.36 mg/dl, 95% CI: -3.67 to 0.95) and an increase in haptoglobin (mean change: 0.26 g/L). Patient-reported outcomes (PROs), assessed via the Pyruvate Kinase Deficiency Diary and Pyruvate Kinase Impact Assessment, showed significant improvements, with mean changes of -4.95 (95% CI: -6.711 to -3.19) and − 5.97 (95% CI: -9.87 to -2.06), respectively. Adverse effects were generally mild, with the most common being headache, nausea, elevated alanine aminotransferase, and nasopharyngitis.

Mitapivat substantially improves hemoglobin levels, hemolysis markers, and PROs, maintaining an acceptable safety profile. Nevertheless, additional, larger-scale randomized controlled trials across diverse age groups remain necessary to further corroborate these findings.