Agios Pharmaceuticals announced positive results from its Phase 3 ENERGIZE-T study, revealing that mitapivat significantly reduced transfusion burden in adult patients with transfusion-dependent alpha- or beta-thalassemia. The study, presented at the 66th American Society of Hematology (ASH) Annual Meeting, demonstrated a statistically significant reduction in transfusion burden compared to placebo, marking a potential advancement in thalassemia treatment.
ENERGIZE-T Trial: Key Findings
The ENERGIZE-T trial, a Phase 3, double-blind, randomized, placebo-controlled, and multicenter study, enrolled 258 patients globally. Participants were administered either mitapivat 100 mg twice daily (BID) or a matched placebo over a 48-week period. The primary endpoint, transfusion reduction response (TRR), was 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 to baseline.
The trial met its primary endpoint, with 30.4% of patients in the mitapivat arm achieving TRR compared to 12.6% in the placebo arm (p=0.0003). Key secondary endpoints also demonstrated statistically significant reductions in transfusion burden with mitapivat compared to placebo. Specifically, 9.9% of patients in the mitapivat arm achieved transfusion independence, compared to 1.1% in the placebo arm.
Maria Domenica Cappellini, M.D., professor of Internal Medicine at the University of Milan, Italy, noted, "Treatment options for patients with transfusion-dependent thalassemia are extremely limited, and transfusions carry serious risks... There is a significant need for alternative treatments to manage this debilitating disease."
Safety and Tolerability
Overall, the incidence of adverse events (AEs) during the 48-week double-blind period was similar between the mitapivat and placebo arms. Treatment-emergent adverse events (TEAEs) were reported in 90.1% of patients on mitapivat and 83.5% on placebo. Common TEAEs in the mitapivat arm included headache, upper respiratory tract infection, initial insomnia, diarrhea, and fatigue. Serious TEAEs were reported in 11.0% and 15.3% of patients on mitapivat and placebo, respectively.
Regulatory Submissions and Future Directions
Based on the ENERGIZE and ENERGIZE-T study results, Agios has filed regulatory applications for mitapivat (PYRUKYND®) in the U.S., European Union, Kingdom of Saudi Arabia, and United Arab Emirates for the treatment of adult patients with non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia.
Sarah Gheuens, M.D., Ph.D., chief medical officer and head of R&D at Agios, stated, "We are confident that this comprehensive data package will highlight mitapivat’s effectiveness in treating patients with thalassemia with the convenience of an oral medication. We look forward to collaborating with regulators with the goal of bringing this novel therapy to patients with thalassemia as quickly as possible."
Addressing Unmet Needs in Thalassemia
Thalassemia, a rare inherited blood disorder, results in reduced hemoglobin production and chronic anemia. Patients often require regular blood transfusions, leading to complications such as iron overload and organ damage. Currently, there are no approved disease-modifying therapies that address the underlying pathophysiology of thalassemia across all transfusion requirements and genotypes. Mitapivat represents a potential disease-modifying treatment that could significantly improve the lives of patients with thalassemia.
