Agios Pharmaceuticals, Inc. announced that the global Phase 3 ENERGIZE-T study of mitapivat in adults with transfusion-dependent (TD) alpha- or beta-thalassemia achieved its primary endpoint of transfusion reduction response. Statistical significance was also achieved for all key secondary endpoints evaluating additional measures of reduction of transfusion burden compared to placebo. With the positive data generated in the Phase 3 ENERGIZE-T and ENERGIZE studies of mitapivat in patients with alpha- or beta- thalassemia regardless of transfusion needs, the company intends to submit a marketing application for PYRUKYND® (mitapivat) in the U.S. by the end of 2024 based on all available data from both studies.

The company also plans to submit marketing applications in Europe and the Gulf Cooperation Council (GCC) countries. Topline results for the Phase 3 ENERGIZE-T study were as follows: A total of 258 patients were enrolled in the study, with 171 randomized to mitapivat 100 mg twice-daily (BID) and 87 randomized to matched placebo. 155 patients (90.6%) in the mitapivat arm and 83 patients (95.4%) in the placebo arm completed the 48-week double-blind period of the study.

The study met its primary endpoint of transfusion reduction response (TRR, defined as a =50% reduction in transfused red blood cell (RBC) units with a reduction of =2 units of transfused RBCs in any consecutive 12-week period through Week 48 compared with baseline). Treatment with mitapivat demonstrated a statistically significant reduction in transfusion burden compared to placebo, as measured by the TRR endpoint. In the mitapivat arm, 30.4% of patients achieved a transfusion reduction response, compared to 12.6% of patients in the placebo arm (2-sided p=0.0003).

Treatment with mitapivat also demonstrated a statistically significant reduction in additional measures of transfusion reduction response compared to placebo as assessed by the three key secondary endpoints: =50% reduction in transfused RBC units in any consecutive 24-week period through week 48 compared with baseline. =33% reduction in transfused RBC units from week 13 through week 48 compared with baseline. =50% reduction in transfused RBC units from week 13 through week 48 compared with baseline.

In addition, a higher proportion of patients in the mitapivat arm (9.9%) compared to the placebo arm (1.1%) achieved the secondary endpoint of transfusion independence (transfusion-free for =8 consecutive weeks through week 48). Overall, during the 48-week double-blind period, incidence of adverse events (AEs) was similar across mitapivat and placebo arms. In the mitapivat arm, 5.8% of the patients experienced an AE leading to discontinuation, compared to 1.2% of patients in the placebo arm. Based on the safety and efficacy data observed in ENERGIZE-T, the company will proceed with the previously stated plans of U.S. regulatory submission by end of this year.

Agios plans to present a more detailed analysis of the Phase 3 ENERGIZE-T data at an upcoming medical meeting. Data from the Phase 3 ENERGIZE study of mitapivat in non-transfusion-dependent thalassemia will be presented at the European Hematology Association 2024 Hybrid Congress in a plenary session on June 15, 2024, and in a poster session on June 14, 2024.