According to research published in Lancet Haematology, mitapivat, an oral activator of pyruvate kinase, reduced transfusion burden in adults with pyruvate kinase deficiency who regularly receive red blood cell (RBC) transfusions.

The researchers conducted ACTIVATE-T, an open-label, single-arm, multinational, phase 3 trial, to evaluate the efficacy and safety of mitapivat in adults with pyruvate kinase deficiency receiving regular transfusions (≥6 episodes in the prior year) ( Identifier: NCT03559699).

Patients were administered oral mitapivat during a 16-week dose-optimization period (5 mg, 20 mg, and 50 mg twice daily) then a 24-week fixed-dose period. The study’s primary endpoint was reduction in transfusion burden, defined as ≥33% reduction in the number of RBC units transfused during the fixed-dose period compared with the patient’s individual historical transfusion burden, standardized to 24 weeks.

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A total of 27 patients (median age, 36.0 years; interquartile range [IQR], 23.0-47.0) female, 74%; male, 26%; White, 74%; Asian, 11%; Not reported, 15%) received ≥1 dose of mitapivat. Patients were exposed to mitapivat for a median duration of 40.3 weeks (IQR, 40.0-41.3).

The study demonstrated that 37% of patients had a reduced transfusion burden by at least 33% (95% confidence interval, 19-58; P =.0002) following treatment with mitapivat.

The researchers reported that the most common treatment-emergent adverse events were increase in alanine aminotransferase (37%), headache (37%), increase in aspartate aminotransferase (19%), fatigue (19%), and nausea (19%). No treatment-related deaths were reported.

“The results of this single-arm, phase 3 trial show that the oral disease-modifying agent, mitapivat, is well tolerated and efficacious in reducing transfusion burden in adults with pyruvate kinase deficiency who receive regular RBC transfusions,” the researchers concluded. The primary limitation of the study was the small sample size, which reflects the rarity of the disease.

Disclosure: This research was supported by Agios Pharmaceuticals. Please see the original reference for a full list of disclosures.


Glenthøj A, van Beers EJ, Al-Samkari H, et al. Mitapivat in adult patients with pyruvate kinase deficiency receiving regular transfusions (ACTIVATE-T): a multicentre, open-label, single-arm, phase 3 trial. Lancet Haematol. Published online August 18, 2022. doi:10.1016/S2352-3026(22)00214-9