1. 80% of patients receiving mitapivat showed hemoglobin response at 12 weeks.

2. Markers of hemolysis, such as bilirubin and LDH, decreased in the treatment period.

Evidence Rating Level: 2 (Good)

Study Rundown: Non-transfusion-dependent thalassemia (NTDT) is a common hemoglobinopathy that affects thousands of people worldwide. Although NTDT patients do not require regular blood transfusions, they are predisposed to many illnesses with limited long-term pharmacotherapy options. It is believed that mitapivat, a pyruvate kinase inhibitor, may aid in the treatment of NTDT ɑ- and β-thalassemia. This open-label trial aimed to assess the safety and efficacy of mitapivat in adults with non-transfusion-dependent (NTD) α- and β- thalassemia. The primary outcome was hemoglobin response at 12 weeks while key secondary outcomes included change in hemolytic markers and erythropoietic activity. According to study results, most patients on mitapivat had a higher hemoglobin by week 12; although, treatment-related adverse events were also common. This study was limited by a small sample size with no placebo group, affecting the validity of results.

Click to read the study in The Lancet

Relevant Reading: Mitapivat versus Placebo for Pyruvate Kinase Deficiency

In-depth [randomized-controlled trial]: Between Dec 28, 2018, and Feb 6, 2020, 27 patients were screened for eligibility across 4 clinical sites in Canada, USA, and UK. Included were patients ≥ 18 years with NTDT and baseline hemoglobin ≤ 10.0 g/dL. Altogether, 20 patients were enrolled (15 β-thalassemia and 5 α-thalassemia) and followed for 24 weeks. Mitapivat was given 50 mg BID for 6 weeks, then increased to 100 mg BID for 18 weeks. The primary outcome of hemoglobin response was achieved in 80% of patients (5 of 5 in α-thalassemia and 11 of 15 in β-thalassemia, p<0.0001). Adverse events were common among those treated with mitapivat (affecting 65% of patients). However, the majority were mild to moderate in nature: insomnia (10 of 20; 50%), dizziness (6 of 20; 30%), and headache (5 of 20; 25%). There were no treatment-related deaths. Overall, findings from this study suggest mixed results around the safety and efficacy of mitapivat. Further research is needed prior to concluding clinical significance.

Image: PD

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