Oral mitapivat beneficial in the treatment of non-transfusion-dependent thalassaemia

Mitapivat, an oral activator of pyruvate kinase, appears to increase haemoglobin concentration and improve fatigue in adults with non-transfusion-dependent (NTD) α-thalassaemia or NTD β-thalassaemia, according to the double-blind phase III ENERGIZE study.

ENERGIZE included 194 adults (63 percent female) with NTD α-thalassaemia or NTD β-thalassaemia and haemoglobin concentrations of not more than 10 g/dL. These participants were randomly assigned to receive mitapivat 100 mg (n=130) or placebo (n=64), taken orally twice a day for 24 weeks.

The primary endpoint was haemoglobin response, defined as at least 1.0-g/dL increase from baseline in mean haemoglobin concentration from week 12 through week 24, evaluated in all participants who were randomly assigned. Safety was analysed in all participants who received at least one dose of study treatment.

One participant in each treatment group did not receive treatment and was therefore excluded from the safety analysis set (mitapivat, n=129; placebo, n=63). Seven patients in the mitapivat group and one in the placebo group discontinued treatment before the end of the 24-week double-blind period.

Haemoglobin response occurred in 42 percent of participants in the mitapivat group as opposed to just one (2 percent) in the placebo group (mean difference, 41 percent, 95 percent confidence interval, 32–50; p<0.0001).

Adverse events (AEs) were documented in 83 percent of mitapivat-treated participants and in 79 percent of those who received placebo. The most common AEs were headache (22 percent vs 10 percent), initial insomnia (14 percent vs 5 percent), nausea (12 percent vs 8 percent), and upper respiratory tract infection (11 percent vs 6 percent). None of the participants died during the study.