Agios' Phase 3 ENERGIZE-T Study of Mitapivat Meets All Endpoints in Transfusion-Dependent Thalassemia

Agios Pharmaceuticals, Inc. has announced promising results from its global Phase 3 ENERGIZE-T study evaluating mitapivat in adults with transfusion-dependent (TD) alpha- or beta-thalassemia. The study achieved its primary endpoint, demonstrating a statistically significant reduction in transfusion burden for patients treated with mitapivat compared to those administered a placebo.

The ENERGIZE-T study builds upon earlier data from the Phase 3 ENERGIZE study, which focused on adults with non-transfusion-dependent thalassemia. Both studies highlight mitapivat's potential as a transformative oral treatment option for thalassemia patients, irrespective of their transfusion needs. Dr. Sarah Gheuens, Agios' Chief Medical Officer, expressed gratitude to the trial participants and collaborators, noting the significance of these findings in providing a new treatment pathway for a disease with limited management options.

Professor Maria Domenica Cappellini from the University of Milan emphasized the transformative potential of mitapivat. Current treatment options for transfusion-dependent thalassemia are limited, with transfusions posing significant risks, such as iron overload and immune reactions. The positive data from the ENERGIZE-T study suggest that mitapivat could offer a safer and more effective alternative for managing this chronic condition.

Study Highlights and Results

The Phase 3 ENERGIZE-T study involved 258 patients, with 171 receiving 100 mg of mitapivat twice daily and 87 receiving a placebo. A significant proportion of patients in the mitapivat arm (90.6%) completed the 48-week double-blind period, compared to 95.4% in the placebo arm.

The primary endpoint of the study was transfusion reduction response (TRR), defined as a ≥50% reduction in transfused red blood cell (RBC) units with a reduction of ≥2 units in any consecutive 12-week period through Week 48 compared with baseline. The results demonstrated that 30.4% of patients treated with mitapivat achieved this response, compared to only 12.6% in the placebo group (with a 2-sided p=0.0003).

Additionally, mitapivat showed statistical significance in reducing the transfusion burden measured through other key secondary endpoints, including:
- ≥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 to Week 48 compared with baseline.
- ≥50% reduction in transfused RBC units from Week 13 to Week 48 compared with baseline.

Moreover, a higher proportion of patients in the mitapivat arm (9.9%) compared to the placebo arm (1.1%) achieved transfusion independence, defined as being transfusion-free for at least eight consecutive weeks through Week 48.

Safety and Adverse Events

The incidence of adverse events (AEs) during the 48-week period was similar between the mitapivat and placebo arms. In the mitapivat group, 5.8% of patients experienced AEs leading to discontinuation, compared to 1.2% in the placebo group.

Given these promising safety and efficacy outcomes, Agios Pharmaceuticals plans to proceed with a U.S. regulatory submission by the end of 2024. Detailed analyses of the Phase 3 ENERGIZE-T data will be presented at a forthcoming medical meeting, while data from the ENERGIZE study will be showcased at the European Hematology Association 2024 Hybrid Congress.

Future Directions

Agios intends to submit marketing applications for mitapivat in the U.S., Europe, and Gulf Cooperation Council (GCC) countries based on the comprehensive data from the ENERGIZE and ENERGIZE-T studies. If approved, mitapivat could represent a significant advancement in the care of thalassemia patients, offering an effective and convenient oral treatment option.

The ENERGIZE-T study underscores the potential of mitapivat to reduce the transfusion burden and improve the quality of life for thalassemia patients, paving the way for a new era in the management of this rare and chronic disease.

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