ENERGIZE: mitapivat meets primary efficacy endpoint in thalassaemia

Mitapivat improved Hb levels and fatigue in participants with non-transfusion-dependent alpha or beta thalassaemia (NTDT) in a phase 3 study.

Improvement in the mean FACIT-Fatigue score

The phase 3 ENERGIZE trial (NCT04770753) randomised 194 participants with α- (n=62) or β-(n=132) NTDT 2:1 to 24 weeks of mitapivat, 100 mg, twice daily, or placebo. Hereafter, all participants received mitapivat for up to 5 years. The primary endpoint was Hb response from week 12 to week 24, compared with baseline. Prof. Ali Taher (American University of Beirut, Lebanon) presented the results1.

“Mitapivat demonstrated a statistically significant improvement in Hb response versus placebo,” expressed Prof. Taher. In the mitapivat arm, 42.3 % of participants had a Hb response, compared with 1.6 % in the placebo arm (P<0.0001). The average Hb response among responders was 1.56 g/dL. Importantly, the researchers reported an improvement in the mean FACIT-Fatigue score for participants on mitapivat compared with those on placebo (+4.85 vs +1.46; P=0.0026). “We also observed improvements in markers of haemolysis and erythropoietic activity,” added Prof. Taher.

Serious adverse events (AEs) were seen in 6.2 % of the participants on mitapivat and 0 % of the participants on placebo. In addition, 3.1 % discontinued the study drug due to AEs. Headache (22.5 %), insomnia (14.0 %), nausea (11.6 %), and upper respiratory tract infection (10.9 %) were the most common ‘any grade’ AEs in the experimental arm.

Mitapivat met the primary and key secondary endpoints in the ENERGIZE trial, realising Hb and fatigue improvement in participants with α- or β-NTDT.

Medical writing support was provided by Robert van den Heuvel.

  1. Taher AT, et al. ENERGIZE: a global, phase 3 study of mitapivat demonstrating efficacy and safety in adults with alpha- or beta-non-transfusion-dependent thalassemia. Abstract #S104, EHA congress 2024, 13–16 June, Madrid, Spain.