Agios Pharmaceuticals, Inc. announced that the global Phase 3 ENERGIZE study of mitapivat in adults with non-transfusion-dependent (NTD) alpha- or beta-thalassemia achieved its primary endpoint of hemoglobin response. Statistical significance was also achieved for both key secondary endpoints associated with change from baseline in FACIT-Fatigue Score and hemoglobin concentration. Agios is also advancing the fully enrolled Phase 3 ENERGIZE-T study of mitapivat in adults with transfusion-dependent alpha- or beta-thalassemia and expects to announce topline data from this 48-week study in mid-2024.

Following the read-out of ENERGIZE-T, the company intends to file for regulatory approval of mitapivat as a treatment for thalassemia by the end of 2024, incorporating all available data from both studies. Topline results for the Phase 3 ENERGIZE study were as follows: A total of 194 patients were enrolled in the study, with 130 randomized to mitapivat 100 mg twice-daily (BID) and 64 randomized to matched placebo. 122 (93.8%) in the mitapivat arm and 62 (96.9%) in the placebo arm completed the 24-week double-blind period of the study.

The study met the primary endpoint of hemoglobin response. Hemoglobin response was defined as an increase of =1 g/dL in average hemoglobin concentrations from Week 12 through Week 24 compared with baseline. Treatment with mitapivat demonstrated a statistically significant increase compared to placebo.

42.3% of patients in the mitapivat arm achieved a hemoglobin response, compared to 1.6% of patients in the placebo arm (2-sided p<0.0001). Treatment with mitapivat also demonstrated statistically significant improvements compared to placebo for both key secondary endpoints: Change from baseline in average FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) subscale score from Week 12 to Week 24. Change from baseline in average hemoglobin concentration from Week 12 to Week 24.

Overall, during the 24-week double-blind period, incidence of adverse events was similar across mitapivat and placebo arms. Four (3.1%) subjects in the mitapivat arm experienced adverse events (AEs) leading to discontinuation; there were no AEs leading to discontinuation in the placebo arm. Agios plans to present a more detailed analysis of the Phase 3 ENERGIZE data at an upcoming medical meeting.