Agios Shares Positive Phase 3 ENERGIZE Study Results on Mitapivat for Non-Transfusion-Dependent Thalassemia at EHA 2024

Agios Pharmaceuticals, Inc., a leader in cellular metabolism and pyruvate kinase (PK) activation, presented promising results from its global Phase 3 ENERGIZE study of mitapivat in adults with non-transfusion-dependent alpha- or beta-thalassemia. The findings were shared in a plenary session at the European Hematology Association 2024 Hybrid Congress in Madrid, Spain. Additionally, a related poster presentation highlighted significant improvements in fatigue and exercise capacity among those treated with mitapivat compared to placebo.

The ENERGIZE study achieved its primary endpoint, showing a statistically significant increase in hemoglobin response rate in patients treated with mitapivat. The study also met key secondary endpoints, demonstrating improvements in both the FACIT-Fatigue Score and hemoglobin concentration from baseline. These results were consistent across all predefined subgroups.

Dr. Sarah Gheuens, Chief Medical Officer and Head of R&D at Agios, emphasized that the data from the ENERGIZE study are compelling. Patients treated with mitapivat showed meaningful improvements in anemia symptoms and overall quality of life. Dr. Gheuens highlighted that these results, along with positive findings from the ENERGIZE-T study of mitapivat in adults with transfusion-dependent thalassemia, underscore the potential of mitapivat to become an essential treatment for various subtypes of thalassemia, all with the convenience of an oral pill. Agios plans to file for regulatory approval in the U.S. by the end of the year.

Professor Ali Taher, an investigator in the ENERGIZE study, expressed his enthusiasm for the potential impact of mitapivat on patients with non-transfusion-dependent thalassemia. He noted that there are currently no approved oral treatments for this condition, which is characterized by anemia, ineffective erythropoiesis, hemolysis, and iron overload. These complications can severely impact patients' quality of life and life expectancy. Based on the study’s data, mitapivat could become a foundational treatment for non-transfusion-dependent thalassemia.

Dr. Kevin Kuo, another investigator in the study, commented on the significant improvements seen in patients treated with mitapivat. These patients experienced meaningful enhancements in fatigue, walking capacity, and other disease symptoms. Dr. Kuo highlighted the urgent need for oral therapies that can improve the daily lives of people with thalassemia. The positive effects of mitapivat on health-related quality of life metrics, particularly for patients with non-transfusion-dependent thalassemia, were especially notable.

Agios enrolled 194 patients in the study, with 130 randomized to receive mitapivat and 64 to placebo. Among those in the mitapivat arm, hemoglobin response rates were higher compared to placebo across all subgroups, including different thalassemia genotypes and baseline hemoglobin concentrations. For instance, 23.8% of alpha-thalassemia patients treated with mitapivat achieved a hemoglobin response, compared to none in the placebo group. In beta-thalassemia patients, 51.1% in the mitapivat arm achieved a hemoglobin response, versus 2.3% in the placebo arm.

Secondary endpoints also showed statistically significant improvements with mitapivat treatment over placebo. For example, the average change in FACIT-Fatigue score was 4.85 in the mitapivat arm compared to 1.46 in the placebo arm. Similarly, the average change in hemoglobin concentration from baseline was significantly higher in the mitapivat arm. Improvements were also observed in the six-minute walk test and various patient-reported outcomes, such as the Patient Global Impression of Change (PGIC) for fatigue and walking capacity.

Overall, the incidence of adverse events was comparable between the mitapivat and placebo arms, with the most common side effects being headache, insomnia, nausea, and upper respiratory tract infection. Only a small percentage of patients (3.9%) in the mitapivat arm experienced severe treatment-related adverse events, and no serious adverse events were reported.

Agios is progressing with its plans to seek regulatory approval for mitapivat as a treatment for thalassemia by the end of 2024, incorporating data from both the ENERGIZE and ENERGIZE-T studies.