Phase III ACTIVATE-T study of Pyrukynd in pyruvate kinase deficiency published in The Lancet Haematology

Data from this study were previously presented at the 2021 European Hematology Association (EHA) Annual Congress.

As reported in the publication, the ACTIVATE-T study met its primary endpoint, with 10 of 27 patients (37%; p=0.0002) receiving Pyrukynd achieving a transfusion reduction response, defined as at least 33% reduction in transfusion burden in the 24-week fixed dose period compared with individual historical transfusion burden standardized to 24 weeks. Nine of these responders achieved an at least 50% reduction. Additionally, six patients (22%) reached transfusion-free status during the fixed-dose period, and three patients (11%) achieved hemoglobin concentrations in the normal range at least once, eight weeks or more after a transfusion, during the fixed dose period. Improvements were also observed for two PK deficiency–specific patient-reported outcome measures. The safety profile of mitapivat was consistent with previously reported data.

The most frequently reported adverse events in patients receiving mitapivat included alanine aminotransferase increase (37%), headache (37%), aspartate aminotransferase increase (18.5%), fatigue (18.5%) and nausea (18.5%). Adverse events of Grade 3 or higher occurred in 8 patients (30%) who received Pyrukynd. No serious adverse events were considered by the investigator to be related to study treatment, and only one patient experienced an adverse event leading to dose reduction.

See: Mitapivat in adult patients with pyruvate kinase deficiency receiving regular transfusions (ACTIVATE-T): a multicentre, open-label, single-arm, phase 3 trial. Andreas Glenthøj et al. The Lancet Haematology Published:August 18 2022 DOI https://doi.org/10.1016/S2352-3026(22)00214-9